IL-6 Gene Research Articles

IL-27 Gene Therapy Ameliorates IPEX Syndrome Caused by Germline Mutation of Foxp3 Gene: A Major Role for Induction of IL-10.

Inactivating mutations of Foxp3, the master regulator of regulatory T cell development and function, lead to immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome in mice and humans. IPEX is a fatal autoimmune disease, with allogeneic stem cell transplant being the only available therapy. In this study, we report that a single dose of adeno-associated virus (AAV)-IL-27 to young mice with naturally occurring Foxp3 mutation (Scurfy mice) substantially ameliorates clinical symptoms, including growth retardation and early fatality. Correspondingly, AAV-IL-27 gene therapy significantly prevented naive T cell activation, as manifested by downregulation of CD62L and upregulation of CD44, and immunopathology typical of IPEX. Because IL-27 is known to induce IL-10, a key effector molecule of regulatory T cells, we evaluated the contribution of IL-10 induction by crossing IL-10-null allele to Scurfy mice. Although IL-10 deficiency does not affect the survival of Scurfy mice, it largely abrogated the therapeutic effect of AAV-IL-27. Our study revealed a major role for IL-10 in AAV-IL-27 gene therapy and demonstrated that IPEX is amenable to gene therapy.

Copy Number Profiling Implicates Thin High-Grade Squamous Intraepithelial Lesions as a True Precursor of Cervical Human Papillomavirus-Induced Squamous Cell Cancer

Full-thickness high-grade squamous intraepithelial lesions (HSIL) are precursors of invasive cervical squamous cell carcinoma (SCC). The World Health Organization and Lower Anogenital Squamous Terminology Standardization Project for human papilloma virus (HPV)–associated lesions divide full-thickness HSIL of the cervix into thin HSIL with thickness of 1 to 9 cell layers and the typical full-thickness HSIL of >10 cell layers. Although HPV oncogene transcripts and p16ink4a overexpression, as markers of transforming HPV infection, are detectable in thin HSIL, the biological significance of thin HSIL in cervical carcinogenesis remains poorly understood. To further characterize thin HSIL, we performed a comparative study of chromosomal copy number variations (CNV), an analysis of dysregulated genes present in the segments with CNV, and a generalized genetic complexity calculation for 31 thin HSIL, 31 thick HSIL, 24 microinvasive SCC (pT1a SCC), and 22 highly invasive SCC samples. Thin HSIL share various CNV and specific dysregulated gene pathways with thick HSIL and invasive SCC. Thin HSIL exhibited an average CNV of 11.6% compared with 14.1% for thick HSIL, 15.5% for pT1a SCC, and 26.6% for highly invasive SCC. The CNV included gains at 1q and 3q (40% and 43%, respectively), partial loss of 3p, and loss of chromosomes 11 (18%), 16 (50%), 20 (35%), and 22 (40%). Pathways affected solely in thin HSIL were those enhancing immune evasion and primarily involved the (interleukin) IL6, IL21, and IL23 genes. ILs are transiently upregulated in response to infection and play a crucial role in mounting antitumor T-cell activity. Deregulation reflects an attempt by the HPV to evade the initial immune response of the host. The primary pathways shared by thick HSIL and invasive SCC were interactions between lymphoid and nonlymphoid cells, NOTCH2 signaling, tight junction interactions (primarily of the claudin family), and FGR2 alternative splicing. Our results show that thin HSIL carry similar genetic changes as thick HSIL and SCC, indicating that thin HSIL are true precursor lesions that can progress to thick HSIL and SCC.

Association between host defence peptide IDR-1002 and ciprofloxacin: Effects on human dental pulp cells.

To evaluate the effects of the association of host defence peptide IDR-1002 and ciprofloxacin on human dental pulp cells (hDPSCs). hDPSCs were stimulated with ciprofloxacin and IDR-1002. Cell viability (by MTT assay), migration capacity (by scratch assay), production of inflammatory and anti-inflammatory mediators by hDPSCs (RT-PCR) and osteogenic differentiation (alizarin red staining) were evaluated. Phenotypic profile of hDPSCs demonstrated 97% for positive marked mesenchymal stem cell. Increased pulp cell migration and proliferation were observed after 24 and 48 h of exposure to IDR-1002 with ciprofloxacin. Mineral matrix formation by hDPSCs was observed of the association while its reduction was observed in the presence of peptide. After 24 h, the association between ciprofloxacin and IDR-1002 significantly downregulated TNFRSF-1, IL-1β, IL-8, IL-6 and IL-10 gene expression (p ≤ 0.0001). The association between the IDR-1002 and ciprofloxacin showed favourable immunomodulatory potential, emerging as a promising option for pulp revascularisation processes.

Exploration of IL-32 (rs45499297) gene variations in EBV and MS patients

Interleukin-32 is a multifunctional cytokine linked to a variety of illnesses and inflammatory disorders, the central nervous system is affected by the chronic inflammatory disease known as multiple sclerosis (MS). Studies about found relationship between them are rare and inconclusive specially when MS patients with Epstein-Barr virus (EBV) positive. Recently, IL-32 identified increase and considers proinflammatory following EBV infection. A case-control study (79 MS patients and 108 controls) for the purpose of investigating T/C genotype of (rs45499297) in all participant then identify their role in MS and EBV patients by Restriction fragment length polymorphism (RFLP) technique. The results appeared that alleles and genotype (rs45499297) was no significant differences between MS patients and healthy controls, also between groups of expanded disability status scale in MS patients but with EBV infection was results appeared that allele C of( rs45499297) more effector in MS patients than controls. The mean of EBV load among multiple sclerosis patients according to sex, EDSS, and therapy line the results revealed that elevated viral load in male, EDSS ≥ 3.0 and in second line therapy compare to opposite groups. In conclusion, the study indicated the role of sex and MS activity in susceptibility to EBV reactivation. However, analysis of the IL-32 gene variants (rs45499297) may influence susceptibility to EBV along with MS associated with the allele C occurrence.

Post-stress changes in il-6 and bdnf mRNA levels in the hippocampus and blood of rats with a genetically determined contrast level of nervous system excitability

Neuroinflammation is considered as one of the mechanisms by which stress can potentially lead to a disturbance of the functions of the central nervous system. The presence of neuroimmune dysfunction after stress, and what genetic factors increase the risk of post-stress neuroinflammation has not been sufficiently investigated. Genetically determined excitability of the nervous system is a promising marker of individual vulnerability to stress, manifested in post-stress disorders associated with the specifics of the formation of neuroinflammation.The aim of this work was to study post-stress changes in the expression of pro-inflammatory il-6 genes in the blood and hippocampus and anti-inflammatory cytokine bdnf in the blood of rats with genetically determined high and low levels of excitability of the nervous system. Breeding animals were used, males of two strains of rats aged 5 months: with a high threshold (HT) of excitability of the nervous system (low excitable) and a low threshold (LT) of excitability of the nervous system (high excitable) from the biological collection of the Pavlov Institute of Physiology of the Russian Academy of Sciences. The stress model is a long-term emotional and painful stress according to the scheme of K. Hecht. Experimental and control animals were decapitated 24 hours, 7 days and 24 days after the end of stress exposure. Changes in the mRNA level of the il-6 and bdnf genes were evaluated using real-time PCR.Chronic stress led to a significant increase in the level of il-6 mRNA in the hippocampus only in high excitable animals 24 days after the end of stress. In the blood, the mRNA level of this cytokine increased only in low-excitable rats. The expression of the bdnf gene in blood did not change in response to stress in any of the strains.

UPLC-QTOF-MS characterized, herbal medicine, pancogrit modulates NF-κB and JAK2/STAT3 signaling pathways in cell-based model of TNF-α dependent acute pancreatitis

Acute pancreatitis develops as a local inflammatory condition of the pancreas due to a wide range of factors including overdose of alcohol or drugs, gall stones, etc. At present, medications based on herbal formulations have gained importance due to their better safety profile. Current study assessed the pharmacological effects of Pancogrit, an herbal medicine, in caerulein and TNF-α-induced in vitro pancreatitis models. A comprehensive evaluation of phytometabolites present in Pancogrit was conducted and 85 phytometabolites were identified through UPLC-QTOF-MS and UPLC-UV. The bioactivity and mode of action of Pancogrit were assessed in caerulein-induced AR42J (rat pancreatic acinar) cells, TNF-α-induced PANC-1 (human pancreatic duct) cells, and NF-κB reporter cells. Pancogrit was found to decrease the elevated amylase and lipase activity in caerulein-induced AR42J cells. It ameliorated the increased ROS levels, IL-6, IL-8 release and NF-κB activity in TNF-α-induced PANC-1 and NF-κB reporter cells. Pancogrit also downregulated IL-6, IL-1β, ICAM-1, and STAT3 gene expression in PANC-1 cells. Moreover, Pancogrit inhibited the protein expression levels of phosphorylated STAT3, phosphorylated and total JAK2 in TNF-α-induced PANC-1 cells. Taken together, Pancogrit is a clinically relevant therapeutic agent for mitigation of pancreatitis.

Direct Current Electrical Stimulation Shifts THP-1-Derived Macrophage Polarization towards Pro-Regenerative M2 Phenotype.

A macrophage shift from the M1 to the M2 phenotype is relevant for promoting tissue repair and regeneration. In a previous in vivo study, we found that direct current (DC) electrical stimulation (EStim) increased the proportion of M2 macrophages in healing tissues and directed the balance of the injury response away from healing/scarring towards regeneration. These observations led us to hypothesize that DC EStim regulates macrophage polarization towards an M2 phenotype. THP-1-derived M0, M1 (IFN-γ and LPS), and M2 (IL-4 and IL-13) macrophages were exposed (or not: control group) to 100 mV/mm of DC EStim, 1 h/day for three days. Macrophage polarization was assessed through gene and surface marker expressions and cytokine secretion profiles. Following DC EStim treatment, M0 cells exhibited an upregulation of M2 marker genes IL10, CD163, and PPARG. In M1 cells, DC EStim upregulated the gene expressions of M2 markers IL10, TGM2, and CD206 and downregulated M1 marker gene CD86. EStim treatment also reduced the surface expression of CD86 and secretion of pro-inflammatory cytokines IL-1β and IL-6. Our results suggest that DC EStim differentially exerts pro-M2 effects depending on the macrophage phenotype: it upregulates typical M2 genes in M0 and M1 cells while inhibiting M1 marker CD86 at the nuclear and protein levels and the secretion of pro-inflammatory interleukins in M1 cells. Conversely, M2 cells appear to be less responsive to the EStim treatment employed in this study.

Expression of IL-8 Gene in Rainbow Trout (Oncorhynchus mykiss) Leucocytes Fed with Uryani plum (Prunus domestica) Extract

Expression of IL-8 Gene in Rainbow Trout (Oncorhynchus mykiss) Leucocytes Fed with Uryani plum (Prunus domestica) Extract

The Effect of Propolis Extract from Sumatra, Indonesia on Escherichia coli and IL-6 Gene Expression in Male Wistar Rats Fed with a High-Fat Diet

The Effect of Propolis Extract from Sumatra, Indonesia on Escherichia coli and IL-6 Gene Expression in Male Wistar Rats Fed with a High-Fat Diet

In Vitro Investigation of Pulsed Electromagnetic Field Stimulation (PEMF) with MAGCELL® ARTHRO on the Regulatory Expression of Soluble and Membrane-Bound Complement Factors and Inflammatory Cytokines in Immortalized Synovial Fibroblasts.

Pulsed electromagnetic field stimulation (PEMF) is gaining more attention as a non-invasive arthritis treatment. In our study, immortalized synovial fibroblasts (K4IM) derived from a non-arthritic donor were exposed to MAGCELL® ARTHRO, a PEMF device, with 105 mT intensity, 8 Hz frequency, and 2 × 2.5 min sessions conducted thrice with a 1 h interval, to understand the underlying mechanism in regard to the complement system. Additionally, tumor necrosis factor (TNFα, 10 ng/mL) pre-treatment prior to PEMF stimulation, as well as 3-day versus 6-day stimulation, were compared. Gene expression of C4b binding protein-alpha and -beta (C4BPα, C4BPβ), complement factor (CF)-H, CFI, CD55, CD59, Interleukin (IL-6) and TNFα was analyzed. Immunofluorescence staining of CD55, CD59, and Ki67 was conducted. Results showed the absence of C4BPα gene expression, but C4BPβ was present. One and three days of PEMF stimulation caused no significant changes. However, after six days, there was a significant increase in CD55, CFH, and CD59 gene expression, indicating cytoprotective effects. Conversely, IL-6 gene expression increased after six days of stimulation and even after a single session in TNFα pre-stimulated cells, indicating a pro-inflammatory effect. PEMF's ambivalent, i.e., enhancing complement regulatory proteins and pro-inflammatory cytokines, highlights its complexity at the molecular level.

Effects of dietary astaxanthin on immune status and lipid metabolism in gilthead seabream (Sparus aurata)

Astaxanthin (AX) is a carotenoid known to have one of the highest documented antioxidant capacities and has attracted considerable scientific and commercial interest. The incorporation of AX into aquaculture practices has been associated with improved pigmentation, modulation of the immune and endocrine systems, stress reduction, reproductive efficiency and general fish health. This study describes the effects of dietary AX (0, control, 20, 100 and 500 mg kg−1 AX per kg of diet) for 15 and 30 days on growth performance, immune and antioxidant status, histology and gene expression in gilthead seabream (Sparus aurata). Fish fed diets enriched with 500 mg kg−1 of AX for 15 days decreased in skin mucus peroxidase activity while at 30 days of trial, fish fed a diet supplemented with 20 mg kg−1 AX increased the peroxidase activity in serum. In addition, bactericidal activity against Vibrio harveyi increased in the skin mucus of fish fed any of the AX supplemented diets. Regarding antioxidant activities in the liver, catalase and glutathione reductase were decreased and increased, respectively, in fish fed a diet supplemented with 500 mg kg−1 of AX. Finally, although the expression of up to 21 inflammatory and lipid metabolism-related genes was analysed in visceral adipose tissue, only the expression of the interleukin 6 (il6) gene was up-regulated in fish fed a diet supplemented with 20 mg kg−1 of AX. The present results provide a detailed insight into the potent antioxidant properties of AX and its possible modulatory effects on the immune status and lipid metabolism of seabream, which may be of interest to the aquaculture sector.

IPSC-Derived Astrocytes and Neurons Replicate Brain Gene Expression, Epigenetic, Cell Morphology and Connectivity Alterations Found in Autism.

We used iPSC-derived neurons and astrocytes of patients with autism vs. controls (5/group) to examine whether they replicate the postmortem brain expression/epigenetic alterations of autism. Additionally, DNA methylation of 10 postmortem brain samples (5/group) was analyzed for genes affected in PSC-derived cells. We found hyperexpression of TGFB1, TGFB2, IL6 and IFI16 and decreased expression of HAP1, SIRT1, NURR1, RELN, GPX1, EN2, SLC1A2 and SLC1A3 in the astrocytes of patients with autism, along with DNA hypomethylation of TGFB2, IL6, TNFA and EN2 gene promoters and a decrease in HAP1 promoter 5-hydroxymethylation in the astrocytes of patients with autism. In neurons, HAP1 and IL6 expression trended alike. While HAP1 promoter was hypermethylated in neurons, IFI16 and SLC1A3 promoters were hypomethylated and TGFB2 exhibited increased promoter 5-hydroxymethlation. We also found a reduction in neuronal arborization, spine size, growth rate, and migration, but increased astrocyte size and a reduced growth rate in autism. In postmortem brain samples, we found DNA hypomethylation of TGFB2 and IFI16 promoter regions, but DNA hypermethylation of HAP1 and SLC1A2 promoters in autism. Autism-associated expression/epigenetic alterations in iPSC-derived cells replicated those reported in the literature, making them appropriate surrogates to study disease pathogenesis or patient-specific therapeutics.

Скрининг хронической болезни почек у детей с помощью алгоритмов машинного обучения.

Late diagnosis of chronic kidney disease (CKD) in children is common. Among the main reasons: lack of awareness among parents and medical personnel, nonspecific symptoms, and difficulties in carrying out diagnostic procedures in children. This leads to serious health consequences for children, including progression of the disease and the need for long-term dialysis therapy or kidney transplantation. P u r p o s e : to identify signs and symptoms in children that have a non-linear impact on CKD using a decision tree (DT) algorithm. M a t e r i a l s a n d m e t h o d s of the study: data were obtained from a single-center prospective cohort study (2011–2022) involving 128 children with CKD stages 1–4 and 30 children in the control group aged 0 to 18 years. An analysis of the anamnesis, hereditary factors, the early period of the child’s development, the results of clinical, paraclinical and genetic examination was carried out. The model was built using a machine learning (ML) algorithm using the decision tree (DR) method. R e s u l t s . The decision tree model identified three variables that jointly influence CKD: protein loss, red blood cells in the urine, and the T598T polymorphic marker of the IL4 gene. The model predicts CKD on the training set with an accuracy of 98.9% [97.3; 100.0]%, sensitivity 97.8% [95.1; 100.0]%, specificity 100.0% [100.0; 100.0]%, ROC-AUC = 100.0% [99.9; 100.0]%.; describes 95.7% [89.1; 100.0]% variance. The resulting regression model is of excellent quality (>90%), because ROC-AUC is 0.98 on the test sample. During the study, the value of the cut-off point (cut-off) of the VLP was determined, which is equal to 0.5. C o n c l u s i o n s . Biomarkers have been identified that will help primary care physicians identify CKD in children at early stages of development. These variables can be easily examined in outpatient and primary care settings. This information may help raise awareness of the diagnosis. Healthcare providers can form groups of patients for more detailed examination, which will reduce the likelihood of wasted time and improve early detection of diseases.

Exudative Age-Related Macular Degeneration: Association between Treatment Efficacy and Single-Nucleotide Variants in RAD51B, TRIB1, COL8A1, COL10A1, IL-9, IL-10, and VEGFA Genes.

Age-related macular degeneration (AMD) is a progressive neurodegenerative condition leading to vision loss and eventual blindness, with exudative AMD posing a heightened risk due to choroidal neovascularization and localized edema. Therapies targeting the VEGF pathway aim to address this mechanism for treatment effectiveness. Our study aimed to evaluate associations between specific genetic variants (RAD51B rs8017304, rs2588809; TRIB1 rs6987702, rs4351379; COL8A1 rs13095226; COL10A1 rs1064583; IL-9 rs1859430, rs2069870, rs11741137, rs2069885, rs2069884; IL-10 rs1800871, rs1800872, rs1800896; VEGFA rs1570360, rs699947, rs3025033, rs2146323) and the response to anti-VEGF treatment for exudative AMD. We enrolled 119 patients with exudative AMD categorized as responders or non-responders based on their response to anti-VEGF treatment. Statistical analysis revealed that RAD51B rs8017304 heterozygous and homozygous minor allele carriers had increased CMT before treatment compared to wild-type genotype carriers (p = 0.004). Additionally, TRIB1 rs4351379 heterozygous and homozygous minor allele carriers exhibited a greater decrease in central macular thickness (CMT) after 6 months of treatment than wild-type genotype carriers (p = 0.030). IL-9 rs1859430, rs2069870, and rs2069884 heterozygous and homozygous minor allele carriers had worse BCVA before treatment than wild-type genotype carriers (p = 0.018, p = 0.012, p = 0.041, respectively). Conversely, IL-9 rs2069885 heterozygous and homozygous minor allele carriers showed greater improvement in BCVA after 6 months compared to wild-type genotype carriers (p = 0.032). Furthermore, VEGFA rs699947 heterozygous and homozygous minor allele carriers had better BCVA before treatment and after 3 and 6 months of treatment than wild-type genotype carriers (p = 0.003, p = 0.022, respectively), with these carriers also exhibiting higher CMT after 6 months of anti-VEGF treatment (p = 0.032). Not all results remained statistically significant under this stringent correction for multiple comparisons. The comparisons of the serum concentrations of IL-10, VEGF-A, and VEGF-R2/KDR between non-responders and responders did not yield statistically significant differences. Our study identified significant associations between genetic variants, including RAD51B rs8017304, TRIB1 rs4351379, IL-9 rs1859430, rs2069870, rs2069884, rs2069885, and VEGFA rs699947, and parameters related to the efficacy of exudative AMD treatment, such as BCVA and CMT.

Effect of Lactiplantibacillus plantarum on the growth, hemato-biochemical, inflammation, apoptosis, oxidative stress markers, involved gens and histopathological alterations in growing rabbits challenged with aflatoxin B1

Aflatoxin B1 (AFB1) is a significant pollutant found in food and feed, posing a threat to public health. The objective of this study was to assess the effect of Lactiplantibacillus plantarum (LACP) against AFB1 in growing rabbits by investigating growth, serum metabolites, immunity, antioxidant capacity, and inflammatory response. A total of 60 growing male rabbits (721.5 ± 2.68g) were allocated to 4 experimental groups. The control group receiving only a basal diet, the AFB1 group (0.3 mg AFB1/kg diet), the LACP group (1 × 109 cfu/g /kg diet), and the combination group (1 × 109 cfu/g + 0.3 mg AFB1/kg diet; AFB1+ LACP) for 8 wk. The administration of AFB1 alone significantly decreased the final body weight, body gain, and feed intake, while significantly increasing the feed conversion ratio (P < 0.05). A significant decline in total proteins and globulins, along with elevated levels of hepatic enzymes (AST, ALP, ALT, and GGT) and renal function markers (creatinine and uric acid), were observed in the AFB1-contaminated group (P < 0.05). Immunoglobulins (IgG and IgM) were significantly decreased, alongside a significant elevation of triglycerides, direct bilirubin, and indirect bilirubin in growing rabbits fed diets with AFB1 (P < 0.05). Supplementing the AFB1 diet with LACP restored the growth reduction, improved liver (AST, ALP, ALT, and GGT) and kidney (creatinine and uric acid) functions, and enhanced immune markers in rabbit serum (P < 0.05). Antioxidant indices (SOD, GSH, and CAT) were significantly decreased in the AFB1 group (P < 0.05). However, the addition of LACP to the AFB1-contaminated diets improved antioxidant capacity and malondialdehyde (MDA) and protein carbonylation (PC) in hepatic tissues of rabbits (P < 0.05). Serum interlukin-4 (IL-4) and interferon gamma (IFN-γ) levels were significantly increased in the AFB1 group (P < 0.05), but the addition of LACP significantly reversed this elevation. AFB1 downregulated the expression of immune-inflammatory genes such Nrf2, IL-10, and BCL-2 genes, while up-regulating the caspase-3 (CASP3) gene (P < 0.05). Supplementing AFB1 diet with LACP significantly decreased the expression of immune-inflammatory genes (Nrf2, IL-10, and BCL-2) and reduced the expression of the apoptotic-related gene CASP3. This study highlights the potential of L. plantarum (1 × 109 cfu/g /kg diet) as a protective agent against AFB1 in growing rabbits by enhancing antioxidant and immune function and reducing apoptosis and inflammation pathways.

The Role of Interferon Regulatory Factors in Liver Diseases.

The interferon regulatory factors (IRFs) family comprises 11 members that are involved in various biological processes such as antiviral defense, cell proliferation regulation, differentiation, and apoptosis. Recent studies have highlighted the roles of IRF1-9 in a range of liver diseases, including hepatic ischemia-reperfusion injury (IRI), alcohol-induced liver injury, Con A-induced liver injury, nonalcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC). IRF1 is involved in the progression of hepatic IRI through signaling pathways such as PIAS1/NFATc1/HDAC1/IRF1/p38 MAPK and IRF1/JNK. The regulation of downstream IL-12, IL-15, p21, p38, HMGB1, JNK, Beclin1, β-catenin, caspase 3, caspase 8, IFN-γ, IFN-β and other genes are involved in the progression of hepatic IRI, and in the development of HCC through the regulation of PD-L1, IL-6, IL-8, CXCL1, CXCL10, and CXCR3. In addition, IRF3-PPP2R1B and IRF4-FSTL1-DIP2A/CD14 pathways are involved in the development of NAFLD. Other members of the IRF family also play moderately important functions in different liver diseases. Therefore, given the significance of IRFs in liver diseases and the lack of a comprehensive compilation of their molecular mechanisms in different liver diseases, this review is dedicated to exploring the molecular mechanisms of IRFs in various liver diseases.

The Effects of Dietary Pterostilbene on the Immune Response, Antioxidant Function, and Jejunal Structure of Broilers.

This experiment was carried out to investigate the effect of pterostilbene (PTE) supplementation in feed on Arbor Acres broilers in terms of serum biochemical parameters, immune and inflammatory responses, antioxidant status, and intestinal morphological structure. For a duration of 42 days, a total of 480 1-day-old Arbor Acres broilers were randomly divided into four groups. Each group was assigned to receive either the basal diet or the basal diet supplemented with 200, 400, or 600 mg/kg of PTE. Each treatment consisted of eight replicates, with 15 chicks per replicate. In comparison with the control group, three PTE treatments significantly increased the lymphocyte transformation rate in the spleen of broilers. The automated biochemical analysis, enzyme-linked immunosorbent assay, and RT-qPCR analysis kits found that 400 mg/kg of PTE significantly increased the serum levels of complement C3, IL-4, and iNOS; reduced the serum levels of IL-6, TNF-α, and mRNA levels of the genes IL-6, IL-8, TNF-α, NLRP3, and IFN-γ; significantly improved the activities of antioxidant enzymes including CAT, GSH-Px, and T-SOD in the jejunum; and significantly reduced the MDA contents in the serum and jejunum of broilers. Nikon microscope observations and ImagePro Plus 6.0 measure results found that 400 mg/kg of PTE supplementation significantly reduced the relative length and weight of the jejunum and improved the jejunal villi structure, resulting in increased intestinal villi, deepened crypt, and an enhanced ratio of villi height to crypt depth (VH/CD). RT-qPCR and Western blot found that dietary PTE also resulted in increased mRNA levels of the genes Claudin-2, Occludin, ZO-1, and Sirt1, and decreased NF-κB protein levels in the jejunum. The results of this study demonstrated that dietary PTE improved the immune function and intestinal health of broilers by reducing inflammation and increasing the antioxidant capacity of the animals.

TNF-α/Stearate Induced H3K9/18 Histone Acetylation Amplifies IL-6 Expression in 3T3-L1 Mouse Adipocytes.

Extensive evidence supports the connection between obesity-induced inflammation and the heightened expression of IL-6 adipose tissues. However, the mechanism underlying the IL-6 exacerbation in the adipose tissue remains unclear. There is general agreement that TNF-α and stearate concentrations are mildly elevated in adipose tissue in the state of obesity. We hypothesize that TNF-α and stearate co-treatment induce the increased expression of IL-6 in mouse adipocytes. We therefore aimed to determine IL-6 gene expression and protein production by TNF-α/stearate treated adipocytes and investigated the mechanism involved. To test our hypothesis, 3T3-L1 mouse preadipocytes were treated with TNF-α, stearate, or TNF-α/stearate. IL-6 gene expression was assessed by quantitative real-time qPCR. IL-6 protein production secreted in the cell culture media was determined by ELISA. Acetylation of histone was analyzed by Western blotting. Il6 region-associated histone H3 lysine 9/18 acetylation (H3K9/18Ac) was determined by ChIP-qPCR. 3T3-L1 mouse preadipocytes were co-challenged with TNF-α and stearate for 24 h, which led to significantly increased IL-6 gene expression (81 ± 2.1 Fold) compared to controls stimulated with either TNF-α (38 ± 0.5 Fold; p = 0.002) or stearate (56 ± 2.0 Fold; p = 0.013). As expected, co-treatment of adipocytes with TNF-α and stearate significantly increased protein production (338 ± 11 pg/mL) compared to controls stimulated with either TNF-α (28 ± 0.60 pg/mL; p = 0.001) or stearate (53 ± 0.20 pg/mL, p = 0.0015). Inhibition of histone acetyltransferases (HATs) with anacardic acid or curcumin significantly reduced the IL-6 gene expression and protein production by adipocytes. Conversely, TSA-induced acetylation substituted the stimulatory effect of TNF-α or stearate in their synergistic interaction for driving IL-6 gene expression and protein production. Mechanistically, TNF-α/stearate co-stimulation increased the promoter-associated histone H3 lysine 9/18 acetylation (H3K9/18Ac), rendering a transcriptionally permissive state that favored IL-6 expression at the transcriptional and translational levels. Our data represent a TNF-α/stearate cooperativity model driving IL-6 expression in 3T3-L1 cells via the H3K9/18Ac-dependent mechanism, with implications for adipose IL-6 exacerbations in obesity.

Inhibitory effects of compounds isolated from Geranium wilfordii on IL-4 production and β-hexosaminidase release in RBL-2H3 cells

This study aimed to investigate the anti-allergic activity of compounds isolated from Geranium wilfordii Maxim. and to suggest potential therapeutic agents for allergies. Nine compounds were isolated from an ethanolic G. wilfordii extract using chromatographic methods and identified chemically and by spectroscopic analysis. These compounds were identified using reported literature data as brevifolin carboxylic acid (1), chlorogenic acid (2), corilagin (3), ellagic acid (4), geraniol (5), kaempferol 3-O-dirhamnoside (6), kaempferol 3-O-neohesperidoside (7), protocatechuic acid (8), and gallic acid (9). All nine identified compounds were assessed for including IL-4 mRNA expression and β-hexosaminidase release in RBL-2H3 cells stimulated with PMA/ionomycin or IgE + DNP-BSA. IL-4 gene expression assay showed that corilagin (3) potently inhibited IL-4 production, and β-hexosaminidase release assay showed that protocatechuic acid (8) markedly reduced histamine release. The study shows that of the nine compounds isolated from G. wilfordii, corilagin (3), and protocatechuic acid (8) are potential treatments for allergy-related diseases.

Comparison of serum levels of IL-10 and IL-11 and mRNA expression of IL-10, IL-11, COX-2, BCL6, and ZEB Family in peripheral blood mononuclear cells (PBMC) of women with polycystic ovary syndrome and healthy individuals

BackgroundThe roles of IL-10, IL-11, COX-2, BCL6, ZEB1, and ZEB2 genes in the potential correlation between polycystic ovary syndrome (PCOS), inflammation, and cancer remain controversial. AimsThis study aimed to compare serum levels of IL-10 and IL-11 and gene expression of IL-10, IL-11, COX-2, BCL6, ZEB1, and ZEB2 in PBMCs of women with PCOS and healthy controls. MethodsA case-control study included 40 women with PCOS as the case group and 40 healthy women as controls. Group matching for age and BMI was performed. Serum levels of IL-10 and IL-11 were assessed using ELISA, while gene expression was measured using real-time PCR. Parameters were compared between groups, and correlations among gene expression and serum levels were explored. ResultsIn comparison to healthy women, women with PCOS exhibited a significant decrease in the expression of COX-2 and IL-10 genes (p<0.001), alongside a significant increase in ZEB2 gene expression (p<0.001). There were no significant differences observed in the expression of IL-11, BCL6, and ZEB1 genes. Furthermore, the serum level of IL-10 was significantly lower in women with PCOS compared to the control group (p<0.001), while no significant difference was found in IL-11 levels. Additionally, no significant correlations were identified between gene expression and serum levels. ConclusionIn women with PCOS, reduced IL-10 gene expression may indicate inflammation and serve as a diagnostic biomarker. However, conflicting findings on COX-2 expression complicate understanding. Elevated ZEB2 expression in PCOS women may lead to infertility, epithelial-mesenchymal transition, and aggressive phenotypes.