Levels Of Nuclear Factor Kappa Research Articles

From small‐scale studies to an encompassing view: Inhibiting inflammation and clinically relevant enzymes with various extracts of Primula vulgaris using in vitro and in silico techniques

AbstractThe genus Primula holds great importance as a source of traditional remedies in various folk medicine systems. In the present study, we investigated the chemical composition and biological properties of different extracts (ethyl acetate, ethanol, ethanol/water, and water) of aerial parts and rhizomes of Primula vulgaris. To determine the chemical profile, the extracts were analyzed using ultrahigh performance liquid chromatography‐high‐resolution mass spectrometry (UHPLC‐HRMS) technique and flavonoids were a major group in this profile. The antioxidant capacity was demonstrated by in vitro chemical tests and in general the ethanol/water extract was found to be the most potent. Enzyme inhibition was studied against various enzymes and ethanol and ethanol/water extracts were more active than others. To assess the anti‐inflammatory potential of the extracts at the molecular level, human dermal fibroblasts (HDF) were treated with lipopolysaccharide (LPS). In vitro experiments showed that the levels of nuclear factor kappa B (NFKB), receptor for advanced glycation endproducts (RAGE), activator protein‐1 (AP‐1), interleukin 6 (IL‐6), interleukin 17 (IL‐17) and tumor necrosis factor (TNF)‐alpha were significantly reduced after treatment with the tested extracts. In addition, the extracts showed an inhibitory effect on the enzymes collagenase, elastase, and hyaluronidase, which are involved in the inflammatory process and destabilization of the extracellular matrix (ECM). P. vulgaris has been observed to modulate matrix metalloproteinase (MMP) synthesis by decreasing the concentration of cellular reactive oxygen species (ROS) during LPS‐induced inflammation. This study also examined the molecular binding and dynamic behavior of various enzymes and proteins associated with skin and infections using ligands derived from the tested extracts. Simulations with AutoDock Vina V1.1.2 and GROMACS 2023.1 showed that isoquercetin in particular showed superior performance in interactions with hyaluronidase. These findings are important for the development of potential therapeutic strategies for skin health and infection control. In summary, P. vulgaris can be considered as an important source of natural bioactive compounds for the development of effective health‐promoting applications in nutraceuticals, pharmaceuticals, and cosmetics

Naringin protects against paclitaxel-induced toxicity in rat testicular tissues by regulating genes in pro-inflammatory cytokines, oxidative stress, apoptosis, and JNK/MAPK signaling pathways.

Paclitaxel (PTX), which is actively used in the treatment of many types of cancer, has a toxic effect by causing increased oxidative stress in testicular tissues. Naringin (NRG) is a natural flavonoid found in plants, and its antioxidant properties are at the forefront. This study aims to investigate the protective feature of NRG in PTX-induced testicular toxicity. Thirty-five male Sprague rats were divided into five groups: control, NRG, PTX, PTX + NRG50, and PTX + NRG100. Rats were administered PTX (2 mg/kg, BW) intraperitoneally once daily for the first 5 days. Then, between the 6th and 14th days, NRG (50 and 100 mg/kg) was administered orally once a day. NRG reduced PTX-induced lipid peroxidation and increased testicular tissue antioxidant capacity (superoxide dismutase, catalase, glutathione peroxidase, and glutathione). While NRG reduces the mRNA expression levels of nuclear factor kappa B, tumor necrosis factor-alpha, interleukin-1 beta, cyclooxygenase-2, interleukin-6, inducible-nitric oxide synthase, mitogen-activated protein kinase 14 (MAPK)14, MAPK15, c-Jun N-terminal kinase, P53, Apaf1, Caspase3, Caspase6, Caspase9, and Bax in testicular tissues; it caused an increase in Nrf2, HO-1, NQO1 and Bcl-2 levels. NRG also improved the structural and functional integrity of testicular tissue disrupted by PTX. PTX-induced sperm damage was alleviated by NRG. NRG showed a protective effect by alleviating the PTX-induced testicular toxicity by increasing oxidative stress, inflammation, apoptosis, and autophagy.

Abstract 310: Cadherin-dependent modulation of chemosensitivity in oral tumor progression

Abstract The progression of healthy oral epithelia to an oral carcinoma often involves aberrant expression of a group of calcium-dependent transmembrane proteins called cadherins. Histological studies of human tumors have demonstrated increased expression of the epithelial-resident placental (P-cadherin) and ectopic expression of the mesenchymal neuronal (N-cadherin) cadherin in oral dysplasia. We hypothesized that these changes in cadherin expression during early oral tumor development could facilitate increases in survival signaling. We genetically modified dysplastic oral keratinocytes to overexpress P-cadherin or suppress endogenous expression of N-cadherin. P-cadherin overexpression and N-cadherin suppression independently elicited a 3-6-fold decrease in apoptosis levels in response to docetaxel treatment compared to similarly treated controls. We found that in untreated dysplastic cells, P- and N-cadherin expression had positive and negative correlations, respectively, with the activation of the survival-associated enzymes focal adhesion kinase (FAK), mitogen-activated protein kinase (MAPK), and AKT kinase. The total levels of nuclear factor kappa B (NFkb) were positively correlated with P-cadherin overexpression and reciprocally correlated with levels of N-cadherin. In docetaxel-treated dysplastic cells, we observed the reverse effect compared to untreated cells: the increased level of N-cadherin was positively correlated with FAK activity whereas FAK activity was suppressed by P-cadherin. P-cadherin expression in docetaxel-treated cells also increased activation of both MAPK and AKT, whereas alteration of N-cadherin levels had no effect. Because N-cadherin levels are known to increase in late-stage oral tumors, we extended these signaling studies to oral squamous carcinoma cells (OSCCs) expressing low or high levels of N-cadherin. In contrast to its suppression of survival pathways in docetaxel-treated dysplastic cells, in docetaxel-treated OSCCs, N-cadherin expression strongly enhanced phosphorylation of MAPK and AKT, and increased expression of NFkb. N-cadherin overexpression during this treatment also increased expression of the antiapoptotic proteins Mcl-1 and suppressed phosphorylation of the apoptotic regulator signal transducer and activator of transcription 3 (pSTAT3). Increase cadherin expression in all untreated cell lines increased expression of an inducer of epithelial to mesenchymal transition, the transmembrane protein mucin-1 (MUC1). N-cadherin overexpression also increased motility in both cell lines. Taken together, our data demonstrate antiapoptotic signaling directed by increased levels of P-cadherin in oral dysplasia and N-cadherin in OSCC, whereas increased levels of N-cadherin in dysplastic cells directed cellular signaling that were associated with a proapoptotic phenotype. Citation Format: Aaron Mody, Cassandra Decker, Kathryn R. Lawson. Cadherin-dependent modulation of chemosensitivity in oral tumor progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 310.

TSG-6 Inhibits the NF-κB Signaling Pathway and Promotes the Odontogenic Differentiation of Dental Pulp Stem Cells via CD44 in an Inflammatory Environment.

In pulpitis, dentinal restorative processes are considerably associated with undifferentiated mesenchymal cells in the pulp. This study aimed to investigate strategies to improve the odonto/osteogenic differentiation of dental pulp stem cells (DPSCs) in an inflammatory environment. After pretreatment of DPSCs with 20 ng/mL tumor necrosis factor-induced protein-6 (TSG-6), DPSCs were cultured in an inflammation-inducing solution. Real-time polymerase chain reaction and Western blotting were performed to measure the expression levels of nuclear factor kappa B (NF-κB) and odonto/osteogenic differentiation markers, respectively. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays were used to assess cell proliferation and activity. Subcutaneous ectopic osteogenesis and mandibular bone cultures were performed to assess the effects of TSG-6 in vivo. The expression levels of odonto/osteogenic markers were higher in TSG-6-pre-treated DPSCs than nontreated DPSCs, whereas NF-κB-related proteins were lower after the induction of inflammation. An anti-CD44 antibody counteracted the rescue effect of TSG-6 on DPSC activity and mineralization in an inflammatory environment. Exogenous administration of TSG-6 enhanced the anti-inflammatory properties of DPSCs and partially restored their mineralization function by inhibiting NF-κB signaling. The mechanism of action of TSG-6 was attributed to its interaction with CD44. These findings reveal novel mechanisms by which DPSCs counter inflammation and provide a basis for the treatment of pulpitis.

RNA is a pro-apoptotic target of cisplatin in cancer cell lines and C. elegans

Cisplatin not only targets DNA but also RNA. However, it is largely unknown whether platinated RNA (Pt-RNA) causes apoptosis and thus contributes to the cytotoxic effects of cisplatin. Consequently, cellular RNA was isolated from HepG2 and LS180 cells, exposed to cisplatin, and the resulting Pt-RNA (20 ng Pt/µg RNA) was transfected into these cancer cell lines or used to treat an apoptosis reporter Caenorhabditis elegans (C. elegans) strain (MD701, expressing CED-1::GFP). Cellular and molecular effects of Pt-RNA were evaluated by luminogenic caspase 3/7 assays, PCR array analysis, and fluorescence microscopy-based quantification of apoptosis in C. elegans gonads. Assuming RNA cross-linking (pseudo double-stranded RNA), the contribution of the Toll-like receptor 3 (TLR3, a sensor of double-stranded RNA) to apoptosis induction in cancer cell lines was investigated by pharmacological TLR3 inhibition and overexpression. In contrast to controls, Pt-RNA significantly enhanced apoptosis in C. elegans (2-fold) and in the cancer cell lines (2-fold to 4-fold). TLR3 overexpression significantly enhanced the pro-apoptotic effects of Pt-RNA in HepG2 cells. TLR3 inhibition reduced the pro-apoptotic effects of Pt-RNA and cisplatin, but not of paclitaxel (off-target control). Gene expression analysis showed that Pt-RNA (but not RNA) significantly enhanced the mRNA levels of nuclear factor kappa B subunit 2 and interleukin-8 in HepG2 cells, suggesting that Pt-RNA is a damage-associated molecular pattern that additionally causes pro-inflammatory responses. Together, this data suggests that not only DNA but also cellular RNA is a functionally relevant target of cisplatin, leading to pro-apoptotic and immunogenic effects.

Albiflorin Alleviates Severe Acute Pancreatitis-Associated Liver Injury by Inactivating P38MAPK/NF-κB Signaling Pathway.

Albiflorin (Alb) is a monoterpenoid component that is commonly found in Paeonia lactiflora Pall. or Paeonia veitchii Lynch. It is known for its impressive anti-oxidant and anti-inflammatory properties. However, the effect of Alb on severe acute pancreatitis (SAP)-associated liver injury has not been fully understood. To investigate this, we conducted a study using a rat model of SAP induced by administering two intraperitoneal injections of 20% L-arginine (3.3g/kg) over a period of 2h. Subsequently, the SAP-induced rats were randomly assigned into different groups with the treatment of gradient doses of Alb (5, 10, and 20mg/kg), with the normal saline as the sham group. The pathological changes in rat livers were evaluated through hematoxylin-eosin staining. Furthermore, the levels of amylase (AMY), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined using specific enzyme-linked immunosorbent assay kits. Moreover, the serum levels of inflammatory factors, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β, were quantified. Finally, immunohistochemical and Western blot analyses were conducted to determine phosphorylation levels of nuclear factor kappa B (NF-κB) p65 and mitogen-associated protein kianse (MAPK) p38 in the liver tissues. TNF-α stimulated liver cells were used as a cell model to further confirm the involvement of NF-κB and p38 in the effect of Alb. Our study revealed that Alb effectively mitigated the hepatic pathological damage in a dose-dependent manner and reduced the levels of indicators associated with hepatic malfunction (AMY, AST, and ALT) in rats with SAP-induced liver injury. Additionally, Alb demonstrated its ability to suppress inflammation and oxidative stress markers in the liver tissues. Alb exerted dose-dependent inhibitory effects by modulating the P38MAPK/NF-κB signaling pathway. Overall, our findings strongly support the hepatoprotective effect of Alb in rats with SAP-induced liver injury, suggesting that Alb protects against SAP-induced liver injury through the suppression of inflammation and oxidative stress via the P38MAPK/NF-κB signaling pathway.

Investigation of the principle of concoction by using the processing excipient Glycyrrhiza uralensis Fisch. juice to reduce the main toxicity of Dioscorea bulbifera L. and enhance its main efficacy as expectorant and cough suppressant

Ethnopharmacological relevanceDioscorea bulbifera L. (Rhizoma Dioscoreae Bulbiferae; RDB) is commonly used as an expectorant and cough suppressant herb but is accompanied by severe hepatotoxicity. Using the juice of auxiliary herbs (such as Glycyrrhiza uralensis Fisch. (Glycyrrhizae Radix et Rhizoma; GRR) juice) in concocting poisonous Chinese medicine is a conventional method to reduce toxicity or increase effects. Our previous study found that concoction with GRR juice provided a detoxifying effect against the major toxic hepatotoxicity induced by RDB, but the principle for the detoxification of the concoction is unknown to date. Aim of the studyThe principle of concoction was investigated by using the processing excipient GRR juice to reduce the major toxic hepatotoxicity of RDB, and the efficacy of RDB as an expectorant and cough suppressant was enhanced. Materials and methodsIn this study, common factors (RDB:GRR ratio, concocted temperature, and concocted time) in the concoction process were used for the preparation of each RDB concocted with GRR juice by using an orthogonal experimental design. We measured the content of the main toxic compound diosbulbin B (DB) and serum biochemical indicators and performed pathological analysis in liver tissues of mice to determine the best detoxification process of RDB concocted with GRR juice. On this basis, the biological mechanisms of target organs were detected by Western blot and enzyme-linked immunosorbent assay at the inflammation and apoptosis levels. Further, the effects of RDB on expectorant and cough suppressant with GRR juice were evaluated by the conventional tests of phenol red expectorant and concentrated ammonia-induced cough. Lastly, the major compounds in the GRR juice introduced to RDB concoction were determined. ResultsRDB concocted with GRR juice significantly alleviated DB content, serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase levels, and improved liver pathological damages. The best detoxification process was achieved by using an RDB:GRR ratio of 100:20 at 120 °C for 20 min. Further, RDB concocted with GRR juice down-regulated the protein levels of nuclear factor kappa B (NF-κB), cyclooxygenase 2 (COX-2), and Bcl-2 related X protein (Bax) in the liver and enhanced the expectorant and cough suppressant effects of RDB. Finally, liquiritin (LQ) and glycyrrhizic acid (GA) in the GRR juice were introduced to the RDB concoction. ConclusionConcoction with GRR juice not only effectively reduced the major toxic hepatotoxicity of RDB but also enhanced its main efficacy as an expectorant and cough suppressant, and that the rationale for the detoxification and/or potentiation of RDB was related to the reduction in the content of the main hepatotoxic compound, DB, the introduction of the hepatoprotective active compounds, LQ and GA, in the auxiliary GRR juice, as well as the inhibition of NF-κB/COX-2/Bax signaling-mediated inflammation and apoptosis.

Slit2 suppresses endotoxin-induced uveitis by inhibiting the PI3K/Akt/IKK/NF-κB pathway.

Uveitis is a devastating intraocular inflammatory disease. The secreted leucine-rich repeat protein slit homologue 2 (Slit2) has been found to be an essential regulator of inflammation. This study aimed to analyse the anti-inflammatory effects and the underlying mechanisms of Slit2 in an endotoxin-induced uveitis (EIU) rat model. In this study, rats with EIU pretreated recombinant human Slit2 (rhSlit2) or a control vehicle by intravitreal injection. The clinical scores were graded under a slit lamp. The protein concentrations and total number of cells in the aqueous humour (AqH) were examined, and the retinal expression of various inflammatory mediators was detected. The levels of nuclear factor-kappa B (NF-κB), phosphorylated NF-κB, IkappaB-a (IκB-a), phosphorylated IκB-a, IKK, phosphorylated IKK, PI3Kp85, phosphorylated PI3Kp85, Akt and phosphorylated Akt were evaluated by western blotting. Treatment with rhSlit2 dramatically diminished the clinical scores of EIU, with significant decreases in inflammatory cell infiltration, protein concentrations, cellulose-like exudates, the production of ICAM-1, MCP-1, TNF-α and IL-6 in the AqH; and adhesion of leucocytes. The PI3K/Akt/IKK/NF-κB pathway was found to be activated in EIU. However, the pre-treatment of rhSlit2 significantly inhibited the production of ICAM-1, MCP-1, TNF-α, and IL-6, and inhibited leucocyte adhesion by modulating the PI3K/Akt/IKK/NF-κB pathway. In conclusion, the intravitreal injection of rhSlit2 alleviated EIU-related inflammation in Sprague-Dawley rats by reducing the proinflammatory cytokines and leucocyte adhesion; in particular, rhSlit2 may inhibit LPS-induced inflammation by inhibiting the activation of PI3K/Akt/IKK/NF-κB signalling pathway. Therefore, rhSlit2 shows significant potential for effectively alleviating immune inflammatory responses in vivo.

Zinc protects against lead-induced testicular damage via modulation of steroidogenic and xanthine oxidase/uric acid/caspase 3-mediated apoptotic signaling in male Wistar rats

Aim This study evaluated the effect of lead, with or without zinc co-administration, on steroidogenic and xanthine oxidase (XO)/uric acid (UA)/caspase 3-mediated apoptotic signaling in the testis. Materials and methods Forty male Wistar rats were divided into four groups at random; vehicle-treated control, zinc-treated, lead-treated, and lead + zinc-treated groups. Results Lead exposure significantly lowered overall weight gain, testicular, epididymal, seminal vesicle, and prostate weights. Also, lead decreased sperm count, viability and motility but increased the fraction of sperm with aberrant morphology. In addition, lead caused a marked rise in the level of UA and XO activity but a decrease in nuclear factor erythroid 2-related factor 2 (Nrf2), reduced glutathione (GSH) as well as total antioxidant capacity (TAC) levels, and superoxide dismutase (SOD) and catalase activities. Furthermore, lead increased the testicular levels of nuclear factor kappa B (NFkB), interleukin-1beta (IL-1β), and tumour necrotic factor-alpha (TNF-α), which were associated with an increase in testicular caspase 3 activity and DNA fragmentation as well as a decline in circulating gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and testicular 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD). These were associated with lead-induced degenerative changes in testicular tissues evidenced by shrunken seminiferous tubules, degeneration and sloughing of germ cells. Co-administration of zinc prevented lead-induced testicular injury by ameliorating oxidative stress, apoptosis, and inflammation through downregulation of XO/UA/caspase 3 pathway and upregulation of testicular 3β-HSD/17β-HSD. Conclusion This study demonstrated that zinc protected against lead-induced testicular toxicity via the downregulation of XO/UA/caspase 3 signaling.

Combining bioinformatics and machine learning to identify common mechanisms and biomarkers of chronic obstructive pulmonary disease and atrial fibrillation.

Patients with chronic obstructive pulmonary disease (COPD) often present with atrial fibrillation (AF), but the common pathophysiological mechanisms between the two are unclear. This study aimed to investigate the common biological mechanisms of COPD and AF and to search for important biomarkers through bioinformatic analysis of public RNA sequencing databases. Four datasets of COPD and AF were downloaded from the Gene Expression Omnibus (GEO) database. The overlapping genes common to both diseases were screened by WGCNA analysis, followed by protein-protein interaction network construction and functional enrichment analysis to elucidate the common mechanisms of COPD and AF. Machine learning algorithms were also used to identify key biomarkers. Co-expression analysis, "transcription factor (TF)-mRNA-microRNA (miRNA)" regulatory networks and drug prediction were performed for key biomarkers. Finally, immune cell infiltration analysis was performed to evaluate further the immune cell changes in the COPD dataset and the correlation between key biomarkers and immune cells. A total of 133 overlapping genes for COPD and AF were obtained, and the enrichment was mainly focused on pathways associated with the inflammatory immune response. A key biomarker, cyclin dependent kinase 8 (CDK8), was identified through screening by machine learning algorithms and validated in the validation dataset. Twenty potential drugs capable of targeting CDK8 were obtained. Immune cell infiltration analysis revealed the presence of multiple immune cell dysregulation in COPD. Correlation analysis showed that CDK8 expression was significantly associated with CD8+ T cells, resting dendritic cell, macrophage M2, and monocytes. This study highlights the role of the inflammatory immune response in COPD combined with AF. The prominent link between CDK8 and the inflammatory immune response and its characteristic of not affecting the basal expression level of nuclear factor kappa B (NF-kB) make it a possible promising therapeutic target for COPD combined with AF.

Preparation of pumpkin oil-based nanoemulsion as a potential estrogen replacement therapy to alleviate neural-immune interactions in an experimental postmenopausal model

As estrogen production decreases during menopause; the brain's metabolism tends to stall and become less effective. Estrogen most likely protects against neurodegeneration. Consequently, a comprehensive study of the benefits of hormone replacement therapy as a neuroprotective effect is urgently required. This study was designed to fabricate pumpkin seed oil nanoparticles (PSO) in nanoemulsion form (PSO-NE) and investigate their potential role in attenuating the neural-immune interactions in an experimental postmenopausal model.Sixty female white albino rats were divided into six groups: control, sham, ovariectomized (OVX), and three OVX groups treated with 17β-estradiol, PSO, and PSO-NE respectively. Transmission Electron Microscopy (TEM), and particle size analyzer were performed for nanoemulsion evaluation. Serum levels of estrogen, brain amyloid precursor protein (APP), serum levels of nuclear factor kappa B (NF-κβ), interleukin 6 (IL-6), transthyretin (TTR), and synaptophysin (SYP) were evaluated. The expression of estrogen receptors (ER-α, β) in the brain tissue was estimated. The findings revealed that the approached PSO-NE system was able to reduce the interfacial tension, enhance the dispersion entropy, lower the system free energy to an extremely small value, and augment the interfacial area. PSO-NE, showed a significant increase in the levels of estrogen, brain APP, SYP, and TTR accompanied with a significant increased in the expression of brain ER-α, β compared to the OVX group. In conclusion, the phytoestrogen content of PSO exhibited a significant prophylactic effect on neuro-inflammatory interactions, ameliorating both estrogen levels and the inflammatory cascades.

ATPIF1 alleviates oxygen glucose deprivation/reoxygenation-induced astrocyte injury in vitro: A rat model of ischemic brain injury.

The role of ATPIF1 in ischemic brain injury is rarely reported. This study explored the effect of ATPIF1 on astrocyte activity under oxygen glucose deprivation/reoxygenation (OGD/R). The study sample was randomly allocated into: 1) control group (blank control); 2) OGD/R group (hypoxia for 6 h/reoxygenation for 1 h); 3) siRNA negative control (NC) group (OGD/R model+siRNA NC); and 4) siRNA-ATPIF1 group (OGD/R model+siRNA-ATPIF1). The OGD/R cell model was established from Sprague Dawley (SD) rats to simulate ischemia/reperfusion injury. Cells in the siRNA-ATPIF1 group were treated with siATPIF1. Ultrastructural changes in the mitochondria were observed using transmission electron microscopy (TEM). Apoptosis, cell cycle, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were detected with flow cytometry. The protein expression levels of nuclear factor kappa B (NF-κB), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), and caspase-3 were detected with western blot. In the model group, the cell structure and the ridge structure were destroyed, and mitochondria edema, outer membrane damage and vacuole-like lesions were observed. Compared with the control group, the OGD/R group had considerably increased apoptosis, G0/G1 phase, ROS content, MMP, and Bax, caspase-3 and NF-κB protein expression, as well as markedly decreased S phase and Bcl-2 protein expression. Compared with the OGD/R group, the siRNA-ATPIF1 group had considerably decreased apoptosis, G0/G1 phase, ROS content, MMP, and Bax, caspase-3 and NF-κB protein expression, as well as remarkably increased S phase and Bcl-2 protein expression. The inhibition of ATPIF1 may alleviate OGD/R-induced astrocyte injury by regulating the NF-κB signaling pathway, inhibiting apoptosis, and reducing the ROS content and MMP in the rat brain ischemic model.

The protective impact of hesperidin against carbimazole-induced hypothyroidism, via enhancement of inflammatory cytokines, histopathological alterations, and Nrf2/HO-1.

The aim of this study was to evaluate the anti-inflammatory, antioxidant, and antiproliferative effects of hesperidin (HSP) and eltroxin (ELT) on hypothyroidism (HPO) induced by carbimazole (CBZ) in white male albino rats. Thirty-two adult rats were categorized into four groups: Group 1, no treatment (control); Group II, treated with CBZ (20 mg/kg); Group III, treated with HSP (200 mg/kg) + CBZ; and Group IV, treated with ELT (0.045 mg/kg) + CBZ. All treatments were provided as oral daily doses for 90 days. Thyroid hypofunction was significantly manifested in Group II. However, increased levels of thyroid hormones, antioxidant enzymes, nuclear factor erythroid 2-related factor 2, heme oxygenase 1, and interleukin (IL)-10, and a decrease in the level of the thyroid-stimulating hormone were observed in Groups III and IV. On the contrary, decreased levels of lipid peroxidation, inducible nitric oxide synthase, tumor necrosis factor α, IL-17, and cyclooxygenase 2 were detected in groups III and IV. The histopathological and ultrastructural findings were ameliorated in Groups III and IV; on the contrary, Group II presented with significant increases in the height and number of layers of the follicular cells. Immunohistochemistry demonstrated a marked increase in thyroglobulin and significant decreases in the levels of nuclear factor kappa B and proliferating cell nuclear antigen in Groups III and IV. These results confirmed the effectiveness of HSP as an anti-inflammatory, antioxidant, and antiproliferative agent in rats with hypothyroidism. Additional studies are required to assess its potential as a novel agent against HPO.

Association between self-rated depressive symptoms and mucosal expression of NF-κ B in patients with upper gastrointestinal symptoms

BackgroundPrevious clinical studies have reported elevated levels of depressive symptoms in selected samples of patients with gastritis. The objective of this study was to examine the associations of specific biomarkers of inflammation expressed in mucosal tissue from the stomach with mood and anxiety symptoms in adult patients with upper gastrointestinal symptoms.MethodsIn this monocentric, observational study, a total of 32 study participants were included who were referred for a routine diagnostic upper endoscopic assessment based on the suspected clinical diagnosis of gastritis. All participants completed the Hospital Anxiety and Depression Scale (HADS) before undergoing gastroscopy. Immunohistochemical stainings from biopsy sections were performed to evaluate the expression level of nuclear factor kappa B (NF-κ B), myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS).ResultsOur findings confirmed that nearly half of the study cohort (n = 13; 41%) displayed positive HADS depression scores above the clinically relevant cut-off level of ≥ 8. Regression models demonstrated that depressive symptoms were significantly and positively associated with the expression level of NF-κ B in biopsies from the upper gastrointestinal tract.ConclusionsIn summary, our study showed a significant association between NF-κ B expression and clinically relevant depressive symptoms in patients with gastritis, as assessed by a self-rated psychometric questionnaire. Further investigations are needed to confirm this relationship and to identify the pathophysiological mechanisms involved.

High dietary arachidonic acid produces excess eicosanoids, and induces hepatic inflammatory responses, oxidative stress and apoptosis in juvenile Acanthopagrus schlegelii

As a functional fatty acid, Arachidonic acid (ARA) plays an important role in immunity due to its metabolites in mammals, which have been extensively studied in mammals. However, studies on the function of metabolites produced by dietary ARA in aquatic animals are not comprehensive and in-depth. Hence, an eight-week feeding trial was conducted to evaluated the regulatory effects of dietary ARA and its metabolites-eicosanoids on inflammation, oxidative stress and apoptosis in the liver of Acanthopagrus schlegelii with an initial weight of 0.99 ± 0.10 g. Six isonitrogenous and isolipidic (41% protein, 14% lipid) diets were formulated with gradient levels of ARA: 0% (ARA0.10), 0.5% (ARA0.59), 1.0% (ARA1.04), 1.5% (ARA1.42), 2.0% (ARA1.94), 2.5% (ARA2.42), respectively, and palmitic acid was used to regulate lipid levels. Results showed that the key enzyme contents of ARA metabolic pathway such as phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2), lipoxygenase (LOX) cytochrome P450 (CYP450), prostaglandin E2 (PGE2), leukotriene C4 (LTC4) and 20-hydroxyeicosatetraenoic acid (20-HETE) in the liver were increased with dietary ARA levels increased. High levels of dietary ARA (1.94% and 2.42%) activated the gene expression levels of nuclear factor kappa B (nf-κb), which were confirmed by the results of immunofluorescence assay. Likewise, the expression levels of pro-inflammatory cytokines (tnf-α and il-1β) were up-regulated by ARA1.94 and ARA2.42 groups. Fish fed with excess ARA level has significantly low antioxidant capacity by decreasing the activity of related antioxidant parameters and down-regulating the expression level of related genes. The pro-apoptotic related genes (bax and caspase 7/9) were markedly up-regulated as dietary ARA levels increased from 1.04% to 2.42%. Collectively, excess dietary ARA levels (1.92% and 2.42%) produced excess eicosanoids, triggering inflammation via activating NF-κB expression and promoting its nuclear translocation, resulting in oxidative stress by reducing antioxidant parameters (SOD, GSH and GPX), inducing cell apoptosis through up-regulating pro-apoptotic gene expression levels.

The expression levels of NF-κB and IKKβ in epithelial ovarian cancer and their correlation with drug resistance-related genes MDR1, TOPOII, and ERCC1.

To explore the expression levels of nuclear factor kappa B (NF-κB) and inhibitor of nuclear factor kappa B kinase (IKKβ) in epithelial ovarian cancer and the correlation analysis with multi-drug resistance-related genes 1 (MDR1), topoisomerase II (TOPOII) and nucleotide excision repair cross complementary group 1 (ERCC1). Immunohistochemical methods were used to detect the expression levels of NF-κB and IKKβ in epithelial ovarian cancer group (50 cases), ovarian benign tumor group (30 cases), and normal ovary group (10 cases). The expression levels of NF-κB, IKKβ, MDR1, TOPOII and ERCC1 messenger ribonucleic acid (mRNA) and protein were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. Student's t-test and one-way ANOVA were used for comparison of numerical data. Pearson's chi-squared and Fisher's exact tests were carried out for analysis of non-numerical data. The levels of NF-κB, IKKβ, MDR1 and ERCC1 mRNA and protein were increased (P<0.05), and the expression levels of TOPOII were decreased (P<0.05) in the epithelial ovarian cancer group compared to the normal ovary and benign ovarian tumor groups. The expression of NF-κB and IKKβ in epithelial ovarian cancer was significantly increased in patients with higher tumor stage, lower differentiation and presence of lymph node metastasis and positively correlated with MDR1 expression. NF-κB and IKKβ were negatively correlated with the expression of TOPOII and antagonized each other with TOPOII. The expression of NF-κB and IKKβ was positively correlated with the expression of MDR1, and negatively correlated with the expression of TOPOII. The correlation of NF-κB, IKKβ and resistance related genes, including MDR1, TOPOII, ERCC1, can predict the resistance of chemotherapy individuals to chemotherapy.

Effects of Clostridium butyricum on growth performance, meat quality, and intestinal health of broilers.

This study investigated the effects of Clostridium butyricum on the growth performance, meat quality and intestinal health of broilers. A total of 800 one-day-old male Arbor Acres broilers were randomly assigned to two groups with 16 replicates of 25 broilers per group and fed with a basal diet (CON) or a basal diet supplemented with 1.5 × 109 cfu/kg C. butyricum and 5 × 108 cfu/kg C. butyricum at 1-21 d and 22-42 d, respectively (CB). The results indicated that C. butyricum significantly increased the final body weight, average daily gain at 1-42 d in the growth performance of broilers (P < 0.05). Moreover, C. butyricum significantly increased value and pH24h value of breast meat but reduced the drip loss and shear force (P < 0.05). Regarding serum antioxidant indices, C. butyricum significantly increased the total superoxide dismutase (T-SOD) and total antioxidative capacity activities and reduced the malondialdehyde content (P < 0.05). Furthermore, the broilers in the CB demonstrated an increase in jejunal lipase and trypsin activities, villus height (VH) and VH-to-crypt depth ratio at 42 d compared with those in the CON (P < 0.05). C. butyricum also upregulated the intestinal mRNA levels of zonula occludens-1, nuclear factor erythroid 2-related factor 2 (Nrf2), SOD1 and interleukin-10 in the jejunal mucosa (P < 0.05), but it downregulated the mRNA levels of nuclear factor kappa B (NF-κB) and tumor necrosis factor-α (P < 0.05). These results indicate that C. butyricum can improve the growth performance and meat quality of broilers. In particular, C. butyricum can improve the intestinal health of broilers, which is likely to be related to the activation of the Nrf2 signaling pathway and inhibition of the NF-κB signaling pathway.

Activating transcription factor 3 inhibits NF‑κB p65 signaling pathway and mediates apoptosis and cell cycle arrest in cervical cancer cells

BackgroundAs a novel tumor suppressor mediator, activating transcription factor 3 (ATF3) has recently aroused an interest in its possible therapeutic applications in various cancers. In this study, we evaluated the effect of ATF3 overexpression on the cellular level of nuclear factor kappa B (NF-κB) in human papillomavirus (HPV)-infected Ca Ski cells. Further, we examined whether ATF3 could mediate cell cycle arrest and alter the apoptosis level of Ca Ski cells.MethodsThe biological behavior of Ca Ski cells was evaluated prior and subsequent to the overexpression of ATF3 by MTT assay, fluorescence microscopy, cell cycle and annexin V/PI flow cytometric analysis. The effect of ectopic ATF3 expression on the cellular level of NF-κB in HPV-positive cells was evaluated by western blotting assay.ResultsThe overexpression of ATF3 in Ca Ski cells led to significant apoptosis and cell cycle arrest in the G1 phase. Western blotting assay revealed a discernible reduction of NF-κB p65 level in cervical cancer cells.ConclusionATF3 acts as a tumor suppressor factor in HPV16-infected Ca Ski cells and exerts anti-cancer effects on HPV16-related cervical cancer cells potentially by hindering cell growth and inducing cell cycle arrest through the down-regulation of NF-κB. Our results suggest that ATF3 induction or NF-κB suppression may be useful targets for HPV16-related cervical cancer prevention and treatment.

Effects of encapsulated thymol and carvacrol mixture on growth performance, antioxidant capacity, immune function and intestinal health of broilers

This study evaluated the effect of encapsulated thymol and carvacrol mixture (ETCM) on the growth performance, antioxidant capacity, immune function and intestinal health of broilers. In total, 400 one-day-old male Arbour Acres broilers were randomly allocated to two groups with eight replicates of 25 birds each and fed a basal diet (control) or a basal diet supplemented with 150 mg/kg ETCM. The trial lasted 42 days. ETCM supplementation significantly increased (p < .05) average daily gain at d 22–42 and the organ indices of the spleen, pancreas and bursa of Fabricius at d 42. Regarding the serum antioxidant indices, ETCM supplementation significantly increased (p < .05) glutathione peroxidase (GSH-Px) and superoxide dismutase activities and decreased (p < .05) the malondialdehyde content at d 21 and 42. Furthermore, it significantly increased the villus height and villus height-to-crypt depth ratio in the jejunum at d 21 and the ileum at d 42. ETCM supplementation also up-regulated (p < .05) the intestinal mRNA levels of nuclear factor erythroid-2 related factor 2 (Nrf2), GSH-Px, occludin and zonula occludens-1 in the jejunal mucosa, while down-regulated (p < .05) the mRNA levels of nuclear factor kappa B (NF-κB), interleukin 1β, and tumour necrosis factor-alpha. Thus, ETCM positively impacts the growth performance, antioxidant capacity and immune function of broilers. ETCM can also improve intestinal health which may be partially related to the activation of the Nrf2 signalling pathway and the suppression of the NF-κB signalling pathway. HIGHLIGHTS ETCM improves the growth performance, antioxidant capacity and immune function of broilers. ETCM promotes the gut health of broilers, which may be by activating the Nrf2 signalling pathway and suppressing the NF-κB signalling pathway.

Study Of (NF-Κb) Gene Expression As A Biomarker For Development Of Cardiovascular Disease In Type 2 Diabetes

The purpose of this research is to see if there is a link between diabetes type 2 complications and the level of nuclear factor kappa B (NF-κB) overexpression.&#x0D; Ninety blood samples were collected from individuals and divided into three groups, each group involved thirty samples: the first group representing individuals with (hypertensive type 2 diabetes ) ,the second group representing (hypertensive type 2 diabeteswith cardiovascular diseases), and the last group was represented by a control group.&#x0D; mRNA was extracted from blood samples then converted to cDNA by using the (qPCR) technique. The outcomes revealed a significant increase (p&lt;0.05) in expression of mRNANF-κB in both groups compared to the control group and this over- expression in hypertensive type 2 diabetes with cardiovascular diseases more than hypertensive type 2 diabetes. The NF-κB gene was studied in type 2 diabetes and cardiovascular disease in the current study, and it could be a novel target for early CVD therapy in the future.