Interleukin-6 Gene Research Articles

Palmitate-Induced Inflammation and Myotube Atrophy in C2C12 Cells Are Prevented by the Whey Bioactive Peptide, Glycomacropeptide

BackgroundMetabolic diseases are often associated with muscle atrophy and heightened inflammation. The whey bioactive compound, glycomacropeptide (GMP), has been shown to exhibit anti-inflammatory properties and therefore may have potential therapeutic efficacy in conditions of skeletal muscle inflammation and atrophy. ObjectivesThe purpose of this study was to determine the role of GMP in preventing lipotoxicity-induced myotube atrophy and inflammation. MethodsC2C12 myoblasts were differentiated to determine the effect of GMP on atrophy and inflammation and to explore its mechanism of action in evaluating various anabolic and catabolic cellular signaling nodes. We also used a lipidomic analysis to evaluate muscle sphingolipid accumulation with the various treatments. Palmitate (0.75 mM) in the presence and absence of GMP (5 μg/mL) was used to induce myotube atrophy and inflammation and cells were collected over a time course of 6–24 h. ResultsAfter 24 h of treatment, GMP prevented the palmitate-induced decrease in the myotube area and myogenic index and the increase in the TLR4-mediated inflammatory genes tumor necrosis factor-α and interleukin 1β. Moreover, phosphorylation of Erk1/2, and gene expression of myostatin, and the E3 ubiquitin ligases, FBXO32, and MuRF1 were decreased with GMP treatment. GMP did not alter palmitate-induced ceramide or diacylglycerol accumulation, muscle insulin resistance, or protein synthesis. ConclusionsIn summary, GMP prevented palmitate-induced inflammation and atrophy in C2C12 myotubes. The GMP protective mechanism of action in muscle cells during lipotoxic stress may be related to targeting catabolic signaling associated with cellular stress and proteolysis but not protein synthesis.

Impact of interaction between interleukin-6 gene polymorphism and Helicobacter pylori infection on susceptibility to gastric cancer.

This study aimed to evaluate the association between four single nucleotide polymorphisms (SNPs) of the interleukin-6 (IL-6) gene and gastric cancer (GC), and impact of interaction between IL-6 SNPs and Helicobacter pylori (H. pylori ) infection on susceptibility to GC. Logistic regression was used to test the relationships between four SNPs of IL-6 gene and GC susceptibility. A generalized multifactor dimensionality reduction (GMDR) model was employed to assess the interaction effect between IL-6 gene and H. pylori infection on GC risk. Logistic regression analysis indicated that the rs1800795-C allele was associated with increased GC risk, adjusted ORs (95% CI) were 1.80 (1.21-2.41) (CC vs. GG) and 1.68 (1.09-2.30) (C vs. G), respectively. The rs10499563-C allele was associated with decreased risk of GC, and adjusted ORs (95% CI) were 0.62 (0.31-0.93) (TC vs. TT), 0.52 (0.18-0.89) (CC vs. TT) and 0.60 (0.29-0.92) (C vs. T), respectively. GMDR methods found a two-dimensional model combination (including rs1800795 and H. pylori infection) was statistically significant. The selected model had testing balanced accuracy of 59.85% and the best cross-validation consistencies of 10/10 ( P = 0.0107). Compared with H. pylori -negative subjects with rs1800795- GG genotype, H. pylori -positive participants with GC or CC genotype had the highest risk of GC, the OR (95% CI) was 3.34 (1.78-4.97). The rs1800795-C allele was associated with increased GC risk and the rs10499563-C allele was associated with decreased GC risk. The interaction between rs1800795 and H. pylori infection was also correlated with increased risk of GC.

Interleukin-8 involved in Nile Tilapia (Oreochromis niloticus) against bacterial infection

Interleukin 8 (IL8) is vital in promoting inflammation and is a crucial mediator in various physiopathological processes while influencing immunological function. The effect of IL8 on the immunological response to acute bacterial infections in Nile tilapia (Oreochromis niloticus) remains unknown. This work found an IL8 gene from Nile tilapia (On-IL8). It includes a 285 bp open reading frame and codes for 94 amino acids. The transcript levels of On-IL8 were highest in the head-kidney tissue and sharply induced by Streptococcus agalactiae and Aeromonas hydrophila. Besides, in vitro experiments revealed that On-IL8 regulated a variety of immunological processes and promoted inflammatory responses. Moreover, On-IL8 suppressed the NF-κB signaling pathway, consistent with in vitro results. These significant findings serve as the basis for further investigation into how IL8 confers protection to bony fish in opposition to bacterial infections.

Potential mechanisms of different methylation degrees of pectin driving intestinal microbiota and their metabolites to modulate intestinal health of Micropterus salmoides

Four diets containing 8 % cellulose, low methyl-esterified pectin (LMP), high methyl-esterified pectin (HMP) and MMP (half LMP and half HMP) were designed to evaluate the potential mechanisms by which different esterification degrees of pectin drive intestinal microbiota and their metabolites modulating the intestinal health of Micropterus salmoides. The results showed that both dietary LMP and HMP consistently upregulated intestinal zonula occludens protein 1 (Zo-1), Caludin-1, and Caludin-4, and downregulated intestinal tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), and interleukin-1 beta (IL-1β) gene expression (P < 0.05). Dietary HMP separately upregulated intestinal Occludin, nuclear factor erythroid2-related factor 2 (Nrf2), B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated agonist of cell death (BAD) gene expression, as well as the digesta propionate content, OTUs, Sobs, Shannon, Chao, and ACE indices (P < 0.05), whereas dietary LMP decreased digesta arginine, 4-aminobutyric, L-tyrosine, and phenylalanine contents (P < 0.05). Moreover, dietary HMP decreased plasma lipopolysaccharide and d-lactic acid contents and increased intestinal superoxide dismutase and glutathione peroxidase activities and immunoglobulin (Ig) receptor and IgM levels (P < 0.05). Collectively, dietary HMP improves intestinal health by increasing intestinal flora α-diversity and enhancing intestinal mechanical barrier, anti-inflammatory, antioxidant, and immune functions. On the contrary, the interference of dietary LMP with butyrate, tyrosine, arginine, and 4-aminobutyric acid metabolism is the main reason for its detrimental effects on intestinal health.

Modification of histones by the myeloperoxidase-derived oxidant hypochlorous acid (HOCl) alters their reactivity with vascular smooth muscle cells

In the nucleus, histones are essential in the packaging of DNA and the regulation of gene expression. These histones can also be released to the extracellular space by mechanisms such as necrosis and neutrophil extracellular trap (NET) formation. Histones are cytotoxic and cause sterile inflammation, and as a result, have been implicated in tissue damage in several pathologies, including atherosclerosis. Myeloperoxidase (MPO) is also present on NETs, which is catalytically active and able to produce hypochlorous acid (HOCl). This could modify histones and alter their extracellular reactivity. In this study, we compared the reactivity of histones with and without modification by HOCl with primary human coronary artery smooth muscle cells (HCASMCs). Histones induced a loss in viability and cell death primarily by apoptosis, which was attenuated on modification of the histones by HOCl. Exposure of HCASMCs to histones also resulted in the increased expression of the pro-inflammatory genes monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6), and vascular cell adhesion molecule-1 (VCAM-1) and a decrease in intracellular thiols. In addition, there were changes in the expression of the stress related gene heme oxygenase-1 (HO-1). Modification of the histones with HOCl had no significant influence on changes in gene expression or thiol loss, in contrast to the cytotoxicity studies. Together, these studies provide new insight into the pathways by which histones could promote vascular dysfunction, which could be relevant to inflammatory diseases, such as atherosclerosis and sepsis, which are associated with elevated NET release and high circulating histones, respectively.

Association between the interleukin – 6 (IL-6) polymorphism in −174 G/C genotype (rs1800795) with the Covid-19 pathogenicity

BackgroundIn severe cases of COVID-19 with increased levels of inflammatory cytokines such as IL-6, a cytokine storm occurs, which can lead to respiratory failure. Due to the role of the IL-6 gene in respiratory diseases, and the fact that polymorphism of this gene may be one of the factors involved in disease severity, this study aimed to investigate the association of polymorphism-174G > C (rs1800795) of the IL-6 gene with COVID-19. Methods200 individuals were studied in two groups of SARS-COV-2 positive and negative. The PCR-RFLP technique was applied to detect the polymorphism. The PCR products were digested using the NlaIII restriction enzyme. ResultsThere was no association between rs1800795 and COVID-19 disease and disease severity. Among cases with pulmonary complications and cases with high CRP, GG genotype had a significantly higher chance for being infected. Among GG and GC genotypes, the age group of 36–50 had a significantly higher chance of infection. A lower chance of infection was also observed among cases with normal levels of ESR with GG and GC genotypes. Finally, considering cases with the GG genotype, the normal AST level was significantly associated with the disease. Among the age group of 36–50 the GC and CC genotypes were associated with severity. GC genotype had a lower and higher chance of disease severity in cases with high levels of ESR and AST, respectively. ConclusionIn the present study, IL-6 polymorphism in the promoter region of 174 G > C (rs1800795) was not significantly associated with COVID-19 and the disease severity. Considering the result of this study, further analyses are suggested to ensure the association of ESR, AST, and CRP and the rs1800795 polymorphism with COVID-19 and the disease severity.

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.

First transcriptomic insight into the reprogramming of human macrophages by levan-type fructans

Based on stimuli in the biological milieu, macrophages can undergo classical activation into the M1 pro-inflammatory (anti-cancer) phenotype or to the alternatively activated M2 anti-inflammatory one. Drug-free biomaterials have emerged as a new therapeutic strategy to modulate macrophage phenotype. Among them, polysaccharides polarize macrophages to M1 or M2 phenotypes based on the surface receptors they bind. Levan, a fructan, has been proposed as a novel biomaterial though its interaction with macrophages has been scarcely explored. In this study, we investigate the interaction of non-hydrolyzed and hydrolyzed Halomonas levan and its sulfated derivative with human macrophages in vitro. Viability studies show that these levans are cell compatible. In addition, RNA-sequencing analysis reveals the upregulation of pro-inflammatory pathways. These results are in good agreement with real time-quantitative polymerase chain reaction that indicates higher expression levels of C-X-C Motif Chemokine Ligand 8 and interleukin-6 genes and the M2-to-M1 reprogramming of these cells upon levan treatment. Finally, cytokine release studies confirm that hydrolyzed levans increase the secretion of pro-inflammatory cytokines and reprogram IL-4-polarized macrophages to the M1 state. Overall findings indicate that Halomonas levans trigger a classical macrophage activation and pave the way for their application in therapeutic interventions requiring a pro-inflammatory phenotype.

Nervonic acid reduces the cognitive and neurological disturbances induced by combined doses of D-galactose/AlCl3 in mice.

Nervonic acid (NA) is a kind of ultra-long-chain monounsaturated fatty acid, which can repair nerve cell damage caused by oxidative stress. Alzheimer's disease (AD) is a nervous system disease and often accompanied by the decline of learning and memory capacity. In this study, the combined dose of D-galactose/AlCl3 was used to establish a mouse model of AD. Meanwhile, the mice were treated with different doses of NA (10.95 and 43.93 mg/kg). The results showed that NA delayed the decline of locomotion and learning ability caused by D-galactose/AlCl3, increased the activity of total superoxide dismutase, catalase, glutathione peroxidase, and reduced the content of malondialdehyde in vivo. Besides, NA reduced the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), aspartate aminotransferase, alanine aminotransferase, increased the levels of 5-hydroxytryptamine, dopamine, γ-aminobutyric acid, alleviated the cell morphology damage induced by D-galactose/AlCl3 in hippocampus and liver tissue. Furthermore, the intervention of NA upregulated the expression levels of PI3K, AKT, and mTOR genes and downregulated the expression levels of TNF-α, IL-6, and IL-1β genes. Therefore, we speculate the intervention of NA could be an effective way in improving cognitive impairment through the activation of PI3K signaling pathway. These results suggest that NA has the potential to be developed as antioxidant drug for the prevention and early therapy of AD.

Evaluation of deoxythymidine-based cationic amphiphiles as antimicrobial, antibiofilm, and anti-inflammatory agents

ObjectivesWe recently designed a series of cationic deoxythymidine-based amphiphiles that mimic the cationic amphipathic structure of antimicrobial peptides (AMPs). Among these amphiphiles, ADG-2e and ADL-3e displayed the highest selectivity against bacterial cells. In this study, ADG-2e and ADL-3e were evaluated for their potential as novel classes of antimicrobial, antibiofilm, and anti-inflammatory agents. MethodsMinimum inhibitory concentrations of ADG-2e and ADL-3e against bacteria were determined using the broth microdilution method. Proteolytic resistance against pepsin, trypsin, α-chymotrypsin, and proteinase K was determined by radial diffusion and HPLC analysis. Biofilm activity was investigated using the broth microdilution and confocal microscopy. The antimicrobial mechanism was investigated by membrane depolarization, cell membrane integrity analysis, scanning electron microscopy (SEM), genomic DNA influence and genomic DNA binding assay. Synergistic activity was evaluated using checkerboard method. Anti-inflammatory activity was investigated using ELISA and RT-PCR. ResultsADG-2e and ADL-3e showed good resistance to physiological salts and human serum, and a low incidence of drug resistance. Moreover, they exhibit proteolytic resistance against pepsin, trypsin, α-chymotrypsin, and proteinase K. ADG-2e and ADL-3e were found to kill bacteria by an intracellular target mechanism and bacterial cell membrane-disrupting mechanism, respectively. Furthermore, ADG-2e and ADL-3e showed effective synergistic effects when combined with several conventional antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MDRPA). Importantly, ADG-2e and ADL-3e not only suppressed MDRPA biofilm formation but also effectively eradicated mature MDRPA biofilms. Furthermore, ADG-2e and ADL-3e drastically decreased tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) gene expression and protein secretion in lipopolysaccharide (LPS)-stimulated macrophages, implying potent anti-inflammatory activity in LPS-induced inflammation. ConclusionOur findings suggest that ADG-2e and ADL-3e could be further developed as novel antimicrobial, antibiofilm, and anti-inflammatory agents to combat bacterial infections.

Nomilin and its analogue obacunone alleviate NASH and hepatic fibrosis in mice via enhancing antioxidant and anti-inflammation capacity.

Nonalcoholic steatohepatitis (NASH) and hepatic fibrosis are leading causes of cirrhosis with rising morbidity and mortality worldwide. Currently, there is no appropriate treatment for NASH and hepatic fibrosis. Many studies have shown that oxidative stress is a main factor inducing NASH. Nomilin (NML) and obacunone (OBA) are limonoid compounds naturally occurring in citrus fruits with various biological properties. However, whether OBA and NML have beneficial effects on NASH remains unclear. Here, we demonstrated that OBA and NML inhibited hepatic tissue necrosis, inflammatory infiltration and liver fibrosis progression in methionine and choline-deficient (MCD) diet, carbon tetrachloride (CCl4 )-treated and bile duct ligation (BDL) NASH and hepatic fibrosis mouse models. Mechanistic studies showed that NML and OBA enhanced anti-oxidative effects, including reduction of malondialdehyde (MDA) level, increase of catalase (CAT) activity and the gene expression of glutathione S-transferases (GSTs) and Nrf2-keap1 signaling. Additional, NML and OBA inhibited the expression of inflammatory gene interleukin 6 (Il-6), and regulated the bile acid metabolism genes Cyp3a11, Cyp7a1, multidrug resistance-associated protein 3 (Mrp3). Overall, these findings indicate that NML and OBA may alleviate NASH and liver fibrosis in mice via enhancing antioxidant and anti-inflammation capacity. Our study proposed that NML and OBA may be potential strategies for NASH treatment.

Correlations of Interleukin-6 (IL-6) ( G174C and G572C ) gene polymorphisms and sera levels with risk of Coronary Artery Disease in Thi – Qar province

The present study was carried out in the labs of Technical Institute –Al-Nasiriyah /Community Health Department and Nasiriyah Heart Center in Thi- Qar province, during the period of research was extended from January to July 2022 . The aim of study was to determination polymorphisms of IL-6 gene in patients with Coronary Artery Disease and measuring its levels in serum using a technique enzyme-linked immune sorbent adsorptive (ELISA). The study included a total of 100 Iraqi patients with coronary artery disease(CAD) and healthy control group their age between 3-85 years. DNA has been isolated and PCR was performed by using primers specific for genotypes of IL-6 gene (572 C/G and 174 C/G), the results showed that gel electrophoresis for amplified IL-6 gene of CAD patients, gel electrophoresis of 167bp (IL-6 572C/G) PCR products and 198bp PCR product(IL-6 174C/G). Frequency of genotypes for the IL6 gene showed a high frequency of GG genotype compared to the GC and CC genotypes in all study groups , the frequency of G and C allele in IL6 gene was 95 % and 5 %, respectively with significant differences between genotypes in various groups, in the patient group (90 %) had GC genotype, (10%) were heterozygote and had (0%) had CC genotype compare with control group, (100%) had GC genotype, (0%) were heterozygote and had (0%) had CC genotype. The immunological study showed that there was a significant increase of concentrations of (IL-6) in patients compared to the healthy control group. Thus it seems There is no correlation between IL-6 gene polymorphisms and the risk of coronary artery disease in Thi- Qar province and the Serological Assay (ELISA) showed a significant increase in the concentration of IL-6 in patients with coronary artery disease compared with the healthy control group.

Distinct inflammatory signatures of upper and lower body adipose tissue and adipocytes in women with normal weight or obesity.

Upper and lower body fat accumulation poses an opposing obesity-related cardiometabolic disease risk. Depot-differences in subcutaneous adipose tissue (SAT) function may underlie these associations. We aimed to investigate the inflammatory signatures of abdominal (ABD) and femoral (FEM) SAT in postmenopausal women with normal weight or obesity. We included 23 postmenopausal women with normal weight (n = 13) or obesity (n = 10). In vivo secretion of adipokines from ABD and FEM SAT was measured using the arterio-venous balance technique. Adipokine gene expression and adipocyte morphology were examined in ABD and FEM SAT. Furthermore, adipokine expression and secretion were investigated in vitro using differentiated human primary ABD and FEM subcutaneous adipocytes derived from the study participants. Plasma leptin and plasminogen activator inhibitor (PAI)-1 concentrations were higher, and ABD and FEM adipocytes were larger in women with obesity than normal weight. No differences in adipocyte size and blood flow were apparent between ABD and FEM SAT. We found significant release of leptin and monocyte chemoattractant protein (MCP)-1 from ABD and FEM SAT, with higher fractional release of MCP-1 from ABD than FEM SAT. Gene expression of leptin, PAI-1, and tumor necrosis factor-α was lower in ABD than FEM SAT and higher in women with obesity than normal weight. In ABD adipocytes, interleukin-6, PAI-1, and leptin gene expression were higher, while adiponectin and dipeptidyl-peptidase-4 gene expression were lower than in FEM adipocytes. Finally, ABD adipocytes secreted less MCP-1 compared to FEM adipocytes. These findings demonstrate that upper and lower body SAT and adipocytes are characterized by distinct inflammatory signatures in postmenopausal women, which seem independent of adipocyte size.

Anti-multispecies microbial biofilms and anti-inflammatory effects of antimicrobial photo-sonodynamic therapy based on acrylic resin containing nano-resveratrol

BackgroundPolymethylmethacrylate (PMMA)-based removable orthodontic appliances are susceptible to microbial colonization due to the surface porosity, and accumulating the biofilms causes denture stomatitis. the present study evaluated the anti-biofilm and antiinflammatory effects of antimicrobial photo-sonodynamic therapy (aPSDT) against multispecies microbial biofilms (Candida albicans, Staphylococcus aureus, Streptococcus sobrinus, and Actinomyces naeslundii) formed on acrylic resin modified with nanoresveratrol (NR). Materials and methodsFollowing the determination of the minimum biofilm inhibitory concentration (MBIC) of NR, in vitro anti-biofilm activity of NR was evaluated. The antibiofilm efficacy against multispecies microbial biofilm including C. albicans, S. aureus, S. sobrinus, and A. naeslundii, were assessed by biofilm inhibition test and the results were measured. To reveal the anti-inflammatory effects of aPSDT on human gingival fibroblast (HGF) cells, the gene expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were evaluated via quantitative real-time polymerase chain reaction (qRT-PCR). ResultsAccording to the results, the MBIC dose of NR against multispecies microbial biofilm was considered 512 µg/mL. The highest biofilm reduction activity was observed in MBIC treated with aPSDT and 2 × MBIC exposed to light emitting diode (LED) and ultrasound waves (UW). The expression level of TNF-α and IL-6 genes were significantly increased when HGF cells were exposed to multispecies microbial biofilms (P<0.05), while after treatment with aPSDT, the expression levels of genes were significantly downregulated in all groups (P<0.05). ConclusionOverall, NR-mediated aPSDT reduced the growth of the multispecies microbial biofilm and downregulated the expression of TNF-α and IL-6 genes. Therefore, modified PMMA with NR can be serving as a promising new orthodontic acrylic resin against multispecies microbial biofilms and the effect of this new material is amplified when exposed to LED and UW.

The Effect of Eight Weeks of Resistance Training and Testosterone Enanthate Consumption on TNF-α and IL-6 Genes’ Expression in the Kidney Tissue of Female Wistar Rats

Objectives: This study aimed to evaluate the effect of a testosterone enanthate anabolic steroid on the gene expression of inflammatory factors in the kidney tissue of female rats following eight weeks of resistance training. Methods: Twenty-one female Wistar rats weighing 200 ± 20 g, aged eight weeks, were prepared from the Iran Pasture Institute. Following a week for acclimatization, the rats were randomly divided into three groups: control (n = 7), training + placebo (n = 6), and training + testosterone enanthate (n = 8). Resistance training included five days a week of climbing a 1-meter ladder with 26 stairs while bearing weights and two days of rest. In the first week, the weights were equal to 40% of the rats’ body weight. In the following weeks, the weight was increased by 20% per week. The rats were weighed two times a week. In the testosterone group, the rats were injected with 20 mg of testosterone enanthate thrice a week. Forty-eight hours following the last training session and testosterone injection, kidney tissue samples were collected to determine the gene expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) using real-time PCR. Results: The results showed that testosterone consumption significantly increased the gene expression of TNF-α and IL-6 in female rats undergoing resistance training (P = 0.001). Conclusions: The findings of this study demonstrated that using testosterone increased inflammatory factors in the kidney tissue of all female Wistar rats.

Upregulation of XRCC1 DNA Repair Gene, Interleukin-8, and Bcl-2 Antiapoptotic Gene Levels in Kurdish Patients with Gastric Adenocarcinoma.

Gastric cancer (GC) is one of the deadliest tumors due to its competence to invade and metastasize. The DNA repair gene (XRCC1), interleukin-8 (IL-8) gene, and B-cell lymphoma 2 (Bcl-2) gene play a crucial role in the development and progression of GC. This study aimed to evaluate the expression of these target genes in GC patients in the Kurdistan region of Iraq. Gastric cancer tissues were collected from 29 patients diagnosed with gastric adenocarcinoma that underwent gastric resection, and 21 tissue samples were obtained from healthy patients that underwent gastroscopy. The gastric tissues were collected in different hospitals in Erbil and Sulaymaniyah cities in the Kurdistan region of Iraq. Moreover, the data regarding Helicobacter pylori, age, gender, and stage of the disease were recorded and analyzed using GraphPad Prism. The gene expression levels of XRCC1, IL-8, and Bcl-2 from gastric tissue were studied by real-time quantitative polymerase chain reaction. The results showed that H. pylori infection was equally distributed among males and females in the tissues of gastric patients, while most of the H. pylori-negative patients were females. It is also found that gastric patients aged 30-60 years old are more commonly tested for the H. pylori test. Accordingly, in this study, patients diagnosed with gastric inflammation more often tested positive for H. pylori, while patients diagnosed with gastric cancer tested negative for this infection. Additionally, it was found that the target genes (XRCC1, IL-8, and Bcl-2) were significantly upregulated in GC patients, compared to the healthy group. Finally, the result revealed that XRCC1, IL-8, and Bcl-2 were upregulated in the Kurdish patients with GC, compared to the healthy control group. Targeting XRCC1, IL-8, and Bcl-2 genes can be an interesting field and promising strategy for cancer treatment.

Dietary polystyrene nanoplastics exposure alters hepatic glycolipid metabolism, triggering inflammatory responses and apoptosis in Monopterus albus

Microplastics and nanoplastics (MPs and NPs) are abundant, persistent, and widespread environmental pollutants that are of increasing concern as they pose a serious threat to ecosystems and aquatic species. Identifying the ecological effects of NPs pollution requires understanding the effects of changing nanoplastics concentrations in aquatic organisms. Monopterus albus were orally fed three different concentrations of 100 nm polystyrene nanoplastics (PS-NPs): 0.05 %, 0.5 %, and 1 % of the feed for 28 days. Nanoplastics significantly activated the PPAR signaling pathway, Acyl-CoA oxidase 1 (ACOX1), carnitine palmitoyltransferase 1a (CPT1A), angiopoietin-like 4 (ANGPTL4), and phosphoenolpyruvate carboxykinase (PCK) at the mRNA level, resulting in disturbed lipid metabolism. Glutathione peroxidase (GSH-px) activity, catalase (CAT) activity, and malondialdehyde (MDA) were significantly elevated in the high nanoplastics-feeding exposure group, leading to oxidative stress in the liver. Overexpression of the cytokines genes Interleukin 1 (IL1B) and Interleukin-8 (IL8), Tumor necrosis factor alpha (TNF-α), activation of MAPK signaling pathway, and increased gene expression of c-Jun amino-terminal kinases (JNK) and p38 indicate that exposure to NPs may lead to hepatopancreas apoptosis through oxidative stress and inflammation. In summary, dietary PS-NPs exposure alters hepatic glycolipid metabolism, triggering inflammatory responses and apoptosis in M. albus. The results of this study provide valuable ecotoxicological data for a better understanding of the biological fate and effects of nanoplastics in M. albus.

Dexpanthenol protects against lipopolysaccharide-induced acute kidney injury by restoring AQP-2 levels via regulating SIRT-1 signaling pathway.

Acute kidney injury (AKI) is a serious pathology, causing dysfunction of urination and concentration due to damage to kidneys, resulting with blood pressure dysregulation and increased toxic metabolites. Dexpanthenol (DEX), a pantothenic acid analog, has anti-inflammatory and anti-apoptotic properties in various tissues. This study aimed to investigate the protective effects of DEX in systemic inflammation induced AKI. Thirty-two female rats were randomly assigned as control, lipopolysaccharide (LPS), LPS+DEX and DEX groups. LPS (5 mg/kg, single dose on 3rd day, 6 hours before sacrification) and DEX (500 mg/kg/d for 3 days) were administered intraperitoneally. After sacrification, blood samples and kidney tissues were collected. Hematoxylin-eosin, caspase-3 (Cas-3) and tumor necrosis factor alpha (TNF-α) staining were performed on kidney tissues. Total oxidant status (TOS) and total antioxidant status levels were measured with spectrophotometric method. Aquaporin-2 (AQP-2), silent information regulator gene-1 (SIRT1) and interleukin-6 (IL-6) gene expressions were detected with qRT-PCR. In the histopathological analysis, it was observed that DEX ameliorated histopathological changes. In the LPS group, there was an increase in blood urea nitrogen, creatinine, urea, TOS, oxidative stress index, IL-6, Cas-3, and TNF-α levels compared to the control group, while AQP-2 and SIRT1 levels were decreased. However, treatment with DEX reversed all these changes. In conclusion, DEX was found to be effective in preventing inflammation, oxidative stress, and apoptosis in the kidney through the SIRT1 signaling pathway. Thus, the protective properties of DEX suggest that it may be a potential therapeutic agent for kidney pathologies.

The positive effects of dietary arginine on juvenile hybrid snakehead (Channa maculata♀×Channa argus♂) fed high-carbohydrate diets: Liver inflammation antioxidant response, and glucose metabolism

The aim of this study was to investigate the effects of arginine supplementation on liver morphology, antioxidant capacity, inflammatory response, insulin signaling pathway and glucose metabolism in hybrid snakehead. Five experimental diets (2.31 %, 2.42 %, 2.72 %, 2.92 %, and 3.12 % arginine) were prepared by adding different levels of arginine to the basal diet containing high (27 %) level of carbohydrate. The results showed that the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) and glutathione peroxidase (GSH-Px) of fish fed with arginine diets were significantly higher than those in control group (p < 0.05), accompanied by the lower malondialdehyde (MDA) content in the same groups (p < 0.05). There were obvious mild inflammatory cell infiltration and increased perihepatic pancreatic space in control group, while the pathological state of the liver was relieved in fish fed with arginine diets. Dietary arginine supplementation resulted in significantly higher glucose metabolism-related genes glucokinase (GK), phosphoenolpyruvate carboxkinase (PEPCK), glycogen synthase (GS) and pyruvate kinase (PK) and insulin signaling pathway key genes insulin receptor subset-1 (IRS-1), protein kinase B (Akt) and phosphoenolpyruvate carboxykinase (PI3K)(p < 0.05). Immune-related genes transforming growth factor β (TGF-β), heat shock protein 70 (HSP70) and heat shock protein 90 (HSP90) were significantly higher in the arginine supplemented diet than in the control group (p < 0.05). Immune-related genes interleukin-8 (IL8), interleukin-1β (IL1β) and tissue tumor necrosis factor-α (TNF-α) in fish fed with arginine diets were significantly lower than those in control group (p < 0.05). In conclusion, dietary arginine can alleviate the adverse effects of high carbohydrate diet on hybrid snakeheads by improving glucose metabolism and enhancing antioxidant, anti-inflammatory and non-specific immune functions.

In ovo injection of silver nanoparticles modulates some productive traits and hepatic gene expression of broilers exposed to lipopolysaccharide challenge.

This study aimed to evaluate the effectiveness of the embryonic injection of silver nanoparticles (SilNPs) on some productive traits and hepatic gene expression of lipopolysaccharide (LPS)-challenged broilers after a 42d rearing period. 560 fertile eggs were randomly allocated to four groups and received either of the following treatments at d 7 of incubation, control (no injection), placebo (1mL saline), SilNP20 (20mg/kg silver nanoparticles), or SilNP40 (40mg/kg silver nanoparticles). After the incubation, 320 hatchlings experienced a 42d standard rearing period. Live body weight (LBW), feed intake (FI), and feed conversion ratio (FCR) were weekly recorded. At the end of the experiment, two birds from each replicate (n = 8 per treatment) were exposed to LPS intraperitoneal injection at 48, 24, and 12h before slaughter time. They were also used for blood, intestinal, and microbial evaluations. The hepatic mRNA levels of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), transforming growth factor beta (TGF-β), and insulin-like growth factor I (IGF-I) were assessed at d 1 and 42 of the experiment. Adminstration of SiLNPs improved LBW, FI, and FCR and also enhanced liver and spleen weights (P < 0.05). SilNP20 birds had significantly lower bursa of Fabricius weight (P < 0.05). SilNP20 had lower total cholesterol levels than others. There was a significant difference (P < 0.05) between SliNP40 and SilNP20 in the ratio of villus height to crypt width. Compared to control groups, chicks of SilNP20, but not SilNP40, showed a significant increase in the relative expression of TNF-α, IL-6, TGF-β, and IFG-I genes at d 1. On d 42, however, both SilNP20 and SilNP40 had significantly higher TNF-α and TGF-β levels than both controls. Silver nanoparticles did not significantly affect the microflora of the ileum and cecum in the current study. In summary, SilNPs administration to chick embryos showed a long-term positive effect on their productive performance.