Native Mexican black bean purified anthocyanins fractionated by high-performance counter-current chromatography modulate inflammatory pathways.

In addition to their pigment properties, the potential health benefits of anthocyanins have made them a subject of interest in recent years. This study aimed to obtain purified anthocyanin fractions from native Mexican black bean cultivars using Amberlite XAD-7 resin column and HPCCC and evaluate their anti-inflammatory properties using RAW 264.7 cells. The major anthocyanins in the purified anthocyanin fractions were delphinidin 3-glucoside (61.8%), petunidin 3-glucoside (25.2%), and malvidin 3-glucoside (12.2%). Purified anthocyanin fractions at 12.5 µg/mL effectively prevented LPS-induced ERK1/ERK2 phosphorylation and reduced the protein expression of COX-2 and mRNA expression of iNOS. Results showed that purified anthocyanin fractions have the potential to modulate the inflammatory response by inhibiting the production of pro-inflammatory mediators through the ERK1/ERK2 and NF-κB pathways. This study suggests that anthocyanins from black beans could be used as a natural strategy to help modulate inflammation-associated diseases.

Sulforaphane upregulates the mRNA expression of NRF2 and NQO1 in non-dialysis patients with chronic kidney disease.

Sulforaphane (SFN), found in cruciferous vegetables, is a known activator of NRF2 (master regulator of cellular antioxidant responses). Patients with chronic kidney disease (CKD) present an imbalance in the redox state, presenting reduced expression of NRF2 and increased expression of NF-κB. Therefore, this study aimed to evaluate the effects of SFN on the mRNA expression of NRF2, NF-κB and markers of oxidative stress in patients with CKD. Here, we observed a significant increase in the mRNA expression of NRF2 (p = 0.02) and NQO1 (p = 0.04) in the group that received 400 µg/day of SFN for 1 month. Furthermore, we observed an improvement in the levels of phosphate (p = 0.02), glucose (p = 0.05) and triglycerides (p = 0.02) also in this group. On the other hand, plasma levels of LDL-c (p = 0.04) and total cholesterol (p = 0.03) increased in the placebo group during the study period. In conclusion, 400 µg/day of SFN for one month improves the antioxidant system and serum glucose and phosphate levels in non-dialysis CKD patients.

Design and functional characterization of Salmo salar TLR5 agonist peptides derived from high mobility group B1 acidic tail.

Toll-like receptor 5 (TLR5) responds to the monomeric form of flagellin and induces the MyD88-depending signaling pathway, activating proinflammatory transcription factors such as NF-κB and the consequent induction of cytokines. On the other hand, HMGB1 is a highly conserved non-histone chromosomal protein shown to interact with and activate TLR5. The present work aimed to design and characterize TLR5 agonist peptides derived from the acidic tail of Salmo salar HMGB1 based on the structural knowledge of the TLR5 surface using global molecular docking platforms. Peptide binding poses complexed on TLR5 ectodomain model from each algorithm were filtrated based on docking scoring functions and predicted theoretical binding affinity of the complex. Circular dichroism spectra were recorded for each peptide selected for synthesis. Only intrinsically disordered peptides (6W, 11W, and SsOri) were selected for experimental functional assay. The functional characterization of the peptides was performed by NF-κB activation assays, RT-qPCR gene expression assays, and Piscirickettsia salmonis challenge in SHK-1 cells. The 6W and 11W peptides increased the nuclear translation of p65 and phosphorylation. In addition, the peptides induced the expression of genes related to the TLR5 pathway activation, pro- and anti-inflammatory response, and differentiation and activation of T lymphocytes towards phenotypes such as TH1, TH17, and TH2. Finally, it was shown that the 11W peptide protects immune cells against infection with P. salmonis bacteria. Overall, the results indicate the usefulness of novel peptides as potential immunostimulants in salmonids.

Sulforaphane Supplementation Did Not Modulate NRF2 and NF-kB mRNA Expressions in Hemodialysis Patients.

BACKGROUND: Patients with chronic kidney disease (CKD) have reduced expression of erythroid nuclear factor-related factor 2 (NRF2) and increased nuclear factor κB (NF-κB). "Food as medicine" has been proposed as an adjuvant therapeutic alternative in modulating these factors. No studies have investigated the effects of sulforaphane (SFN) in cruciferous vegetables on the expression of these genes in patients with CKD. OBJECTIVE: The study aimed to evaluate the effects of SFN on the expression of NRF2 and NF-κB in patients on hemodialysis (HD). DESIGN AND METHODS: A randomized, double-blind, crossover study was performed on 30 patients on regular HD. Fourteen patients were randomly allocated to the intervention group (1 sachet/day of 2.5 g containing 1% SFN extract with 0.5% myrosinase) and 16 patients to the placebo group (1 sachet/day of 2.5 g containing corn starch colored with chlorophyll) for 2 months. After a washout period of 2 months, the groups were switched. NRF2 and NF-κB mRNA expression was evaluated by real-time quantitative polymerase chain reaction, and tumor necrosis factor alpha and interleukin-6 levels were quantified by enzyme-linked immunosorbent assay. Malondialdehyde was evaluated as a marker of lipid peroxidation. RESULTS: Twenty-five patients (17 women, 55 [interquartile range = 19] years and 55 [interquartile range = 74] months on HD) completed the study. There was no significant difference concerning the expression of mRNA NRF2 (P = .915) and mRNA NF-κB (P = .806) after supplementation with SFN. There was no difference in pro-inflammatory and oxidative stress biomarkers. CONCLUSION: 150 µmol of SFN for 2 months had no antioxidant and anti-inflammatory effect in patients with CKD undergoing HD.

Brief research report pesticide occupational exposure leads to significant inflammatory changes in normal mammary breast tissue.

Studies have documented the high occurrence of several tumors, including female breast cancer, in populations occupationally exposed to pesticides worldwide. It is believed that in addition to direct DNA damage, other molecular alterations that indicate genomic instability are associated, such as epigenetic modifications and the production of inflammation mediators. The present study characterized the profile of inflammatory changes in the breast tissue of women without cancer occupationally exposed to pesticides. In samples of normal breast tissue collected during biopsy and evaluated as negative for cancer by a pathologist, oxidative stress levels were assessed as inflammatory markers through measurements of lipoperoxides and total antioxidant capacity of the sample (TRAP) by high-sensitivity chemiluminescence, as well as levels of nitric oxide (NOx) metabolites. The levels of inflammation-modulating transcription factors PPAR-γ (peroxisome proliferator-activated receptor gamma) and NF-κB (nuclear factor kappa B) were also quantified, in addition to the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin 12 (IL-12). The levels of lipoperoxides, TRAP, and NOx were significantly lower in the exposed group. On the other hand, PPAR-γ levels were increased in the breast tissue of exposed women, with no variation in NF-κB. There was also a rise of TNF-α in exposed women samples without significant variations in IL-12 levels. These findings suggest an inflammatory signature of the breast tissue associated with pesticide exposure, which may trigger mechanisms related to mutations and breast carcinogenesis.

Lactobacillus plantarum CQPC02 intervenes in mouse lupus nephritis by regulating the NF-κB signaling pathway.

A strain of Lactobacillus plantarum CQPC02 (LP-CQPC02) isolated from naturally fermented kimchi was utilized in this investigation. In order to construct an animal model of lupus nephritis, pristane was used. We then used a kit to identify markers in mouse blood and tissues and a quantitative polymerase chain reaction (qPCR) to measure the expression of genes associated to nuclear factor kappa-B (NF-κB) in mouse kidney tissue. According to the results of the experiments, oral administration of LP-CQPC02 LP-CQPC02 may lessen the lupus nephritis-related rise in urine protein as well as the cytokine levels that were rising in the serum and renal tissues, including IL-6, IL-12, tumor necrosis factor alpha, and interferon. Additionally, in mice with nephritis, LP-CQPC02 can lower serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), and raise total protein (TP) and albumin (ALB) levels. In mice with nephritis, LP-CQPC02 can also reduce the positive rate of double-stranded deoxyribonucleic acid (dsDNA). Pathological sections were examined, and it was shown that LP-CQPC02 can lessen tissue damage such incomplete glomerular morphology and inflammatory infiltration brought on by nephritis. In the kidneys of mice with lupus nephritis, LP-CQPC02 can upregulate the expression of inhibitor of NF-κB (IκB-α), downregulate the expression of NF-κB, transforming growth factor-ß1 (TGF-ß1), vascular endothelial growth factor (VEGF), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). Lactobacillus plantarum CQPC02 has been confirmed to have an intervention effect on nephritis in mice and has the potential as a probiotic.

NF-ĸΒ1 knockout reduces IL6 expression under hypoxia in renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common adult renal epithelial cancer, accounting for more than 90% of all renal neoplasms. Clear cell RCC (ccRCC) is the most common subtype of RCC. Most patients with ccRCC have a mutation in the von Hippel-Lindau (VHL) tumor suppressor gene, which encodes a protein that downregulates various intracellular proteins, including hypoxia-inducible factor (HIF). Many molecules have been identified to be responsible for the aggressive phenotype of ccRCC, including the transcription factor nuclear factor kappa B (NF-кB). The increase in NF-кB activity observed in RCC is correlated with an increase in angiogenesis markers, such as interleukin 6 (IL-6). In recent years, several groups have demonstrated the functional role of NF-кB1 in RCC tumorigenicity. Herein, we used the CRISPR/Cas-9 technique to obtain an NF-кB1 knockout-human renal adenocarcinoma cell line. Expression of IL-6 at the mRNA and protein levels was analyzed under normoxia and hypoxia by real time-polymerase chain reaction and multiplex assay, respectively. The CRISPR/Cas9 technique was effective in producing 786-0 knockout cells for NF-κB1 (p105/p50), as confirmed by western blot analysis. Suppression of p50 expression in 786-0 single guide RNA (sg)1, 786-0 sg2 and 786-0 sg3 cells downregulated IL-6 mRNA and protein expression under normoxia and hypoxia. The observed decrease in the differential expression of IL-6 in hypoxia/normoxia is suggestive of a change in cellular responsiveness to hypoxia with respect to IL-6.

Effects of 5α-dihydrotestosterone on the modulation of monocyte/macrophage response to Staphylococcus aureus: an in vitro study.

BACKGROUND: Staphylococcus aureus (S. aureus) is a pathogen responsible for a wide range of clinical manifestations and potentially fatal conditions. There is a paucity of information on the influence of androgens in the immune response to S. aureus infection. In this study, we evaluated the influence of the hormone 5α-dihydrotestosterone (DHT) on mouse peritoneal macrophages (MPMs) and human peripheral blood monocytes (HPBMs) induced by S. aureus. METHODS: An in vitro model of MPMs from BALB/c sham males, orchiectomised (OQX) males, and females was used. Cells were inoculated with 10 µL of S. aureus, phage-type 80 or sterile saline (control) for 6 h. The MPMs of OQX males and females were pre-treated with 100 µL of 10-2 M DHT for 24 h before inoculation with S. aureus. The concentration of the cytokines TNF-α, IL-1α, IL-6, IL-8, and IL-10; total nitrites (NO-2); and hydrogen peroxide (H2O2) were measured in the supernatant of MPM cultures. In addition, the toll-like receptor 2 (TLR2) and nuclear factor kappa B (NF-kB) genes that are involved in immune responses were analysed. For the in vitro model of HPBMs, nine men and nine women of childbearing age were selected and HPBMs were isolated from samples of the volunteers' peripheral blood. In women, blood was collected during the periovulatory period. The HPBMs were inoculated with S. aureus for 6 h and the supernatant was collected for the analysis of cytokines TNF-α, IL-6, IL-12; and GM-CSF, NO-2, and H2O2. The HPBMs were then removed for the analysis of 84 genes involved in the host's response to bacterial infections by RT-PCR array. GraphPad was used for statistical analysis with a p value < 0.05. RESULTS: Our data demonstrated that MPMs from sham males inoculated with S. aureus displayed higher concentrations of inflammatory cytokines and lower concentrations of IL-10, NO-2, and H2O2 when compared with MPMs from OQX males and females. A similar result was observed in the HPBMs of men when compared with those of women. Previous treatment with DHT in women HPBMs increased the production of pro-inflammatory cytokines and decreased the levels of IL-10, NO-2, and H2O2. The analysis of gene expression showed that DHT increased the activity of the TLR2 and NF-kB pathways in both MPMs and HPBMs. CONCLUSIONS: We found that DHT acts as an inflammatory modulator in the monocyte/macrophage response induced by S. aureus and females exhibit a better immune defence response against this pathogen.

NCoA3 upregulation in breast cancer­associated adipocytes elicits an inflammatory profile.

Nuclear receptor coactivator 3 (NCoA3) is a transcriptional coactivator of NF­κB and other factors, which is expressed at relatively low levels in normal cells and is amplified or overexpressed in several types of cancer, including breast tumors. NCoA3 levels have been shown to be decreased during adipogenesis; however, its role in tumor­surrounding adipose tissue (AT) remains unknown. Therefore, the present study assessed the modulation of NCoA3 in breast cancer­associated adipocytes and evaluated its association with the expression of inflammatory markers. 3T3­L1 adipocytes were stimulated with conditioned medium from human breast cancer cell lines and the expression levels of NCoA3 were evaluated by reverse transcription­quantitative (q)PCR. NF­κB activation was measured by immunofluorescence, and tumor necrosis factor and monocyte chemoattractant protein 1 levels were analyzed by qPCR and dot blot assays. The results obtained from the in vitro model were supported using mammary AT (MAT) from female mice, MAT adjacent to tumors from patients with breast cancer and bioinformatics analysis. The results revealed that adipocytes expressing high levels of NCoA3 were mainly associated with a pro­inflammatory profile. In 3T3­L1 adipocytes, NCoA3 downregulation or NF­κB inhibition reversed the expression of inflammatory molecules. In addition, MAT from patients with a worse prognosis exhibited high levels of this coactivator. Notably, adipocyte NCoA3 levels could be modulated by inflammatory signals from tumors. The modulation of NCoA3 levels in synergy with NF­κB activity in MAT in a tumor context could be factors required to establish breast cancer­associated inflammation. As adipocytes are involved in the development and progression of breast cancer, this signaling network deserves to be further investigated to improve future tumor treatments.

Cocoa powder and fermented jackfruit seed flour: A comparative cell-based study on their potential antioxidant and anti-inflammatory activities after simulated gastrointestinal digestion.

BACKGROUND: Jackfruit seed flour can be used as a cocoa aroma replacer with similar technological properties. The purpose of this study was to investigate the in vivo toxicity and in vitro antioxidant activity of fermented jackfruit seed flour (Fjs) and non-alkaline cocoa powder (Nac). RESULTS: Fjs and Nac extracts (Fjs-E and Nac-E) were produced and submitted to in vitro gastrointestinal digestion producing digested fractions named Fjs-D and Nac-D, respectively. Nac-E showed over two-fold higher oxygen radical absorbance capacity (ORAC) than Fjs-E. However, after simulated gastrointestinal digestion (in vitro), there were no significant differences between Nac-D and Fjs-D (P < 0.01). Similarly, the cellular antioxidant activity (CAA) of Nac-D and Fjs-D was not significantly different (P < 0.01). The anti-inflammatory assay in transgenic RAW 264.7 murine macrophages showed that Fjs-E did not affect cell viability up to 300 µg mL-1 (P > 0.05) and reduced by 15% the release of TNF-α (P < 0.05). Fjs-D did not affect cell viability up to 300 µg mL-1 (P > 0.05) and showed 58% reduction of NF-κB activation (P < 0.05), with no effects on TNF-α levels. Treatment with Nac-E up to 300 µg mL-1 did not decrease cell viability (P > 0.05) and reduced the release of TNF-α levels by 34% and 66% at 100 and 300 µg mL-1 , respectively (P < 0.05). Nac-D did not reduce the NF-κB activation or TNF-α levels at any tested concentration. CONCLUSION: Collectively, these findings indicate that Fjs is a safe and promising functional ingredient with biological activities even after gastrointestinal digestion. © 2023 Society of Chemical Industry.

Key role of PIN1 in telomere maintenance and oncogenic behavior in a human glioblastoma model.

PIN1 is the only known enzyme capable of recognizing and isomerizing the phosphorylated Serine/Threonine­Proline motif. Through this mechanism, PIN1 controls diverse cellular functions, including telomere maintenance. Both PIN1 overexpression and its involvement in oncogenic pathways are involved in several cancer types, including glioblastoma (GBM), a lethal disease with poor therapeutic resources. However, knowledge of the role of PIN1 in GBM is limited. Thus, the present work aimed to study the role of PIN1 as a telomere/telomerase regulator and its contribution to tumor biology. PIN1 knockout (KO) LN­229 cell variant using CRISPR/Cas9 was developed and compared with PIN1 LN­229 expressing cells. To study the effect of PIN1 absence, status of NF­κB pathway was evaluated by luciferase reporter gene assay and quantitative PCR. Results revealed that PIN1 deletion in GBM cells diminished the active levels of NF­κB and decrease the transcription of il­8 and htert genes. Then, telomere/telomerase related processes were studied by RQ­TRAP assay and telomere length determination by qPCR, obtaining a reduction both in telomerase activity as in telomere length in PIN1 KO cells. In addition, measurement of SA ß­galactosidase and caspase­3 activities revealed that loss of PIN1 triggers senescence and apoptosis. Finally, migration, cell cycle progression and tumorigenicity were studied by flow cytometry/western blot, Transwell assay and in vivo experiments, respectively. PIN1 deletion decreased migration as well as cell cycle progression by increasing doubling time and also resulted in the loss of LN­229 cell ability to form tumors in mice. These results highlight the role of PIN1 in telomere homeostasis and GBM progression, which supports PIN1 as a potential molecular target for the development of novel therapeutic agents for GBM treatment.

Lactobacillus rhamnosus Restores Antiviral Signaling and Attenuates Cytokines Secretion from Human Bronchial Epithelial Cells Exposed to Cigarette Smoke and Infected with SARS-CoV-2.

Individuals with chronic obstructive pulmonary disease (COPD) are more susceptible to exacerbation crisis triggered by secondary lung infections due to the dysfunction of antiviral signaling, principally via suppression of IFN-γ. Although the probiotic is known for controlling pulmonary inflammation in COPD, the influence of the Lactobacillus rhamnosus (Lr) on antiviral signaling in bronchial epithelium exposed to cigarette smoke extract (CSE) and viruses, remains unknown. Thus, the present study investigated the Lr effect on the antiviral signaling and the secretion of inflammatory mediators from bronchial epithelial cells (16HBE cells) exposed to CSE and SARS-CoV-2. The 16HBE cells were cultured, treated with Lr, stimulated with CSE, and infected with SARS-CoV-2. The cellular viability was evaluated using the MTT assay and cytotoxicity measured by lactate dehydrogenase (LDH) activity. The viral load, TLR2, TLR3, TLR4, TLR7, TLR8, MAVS, MyD88, and TRIF were quantified using specific PCR. The pro-inflammatory mediators were measured by a multiplex biometric immunoassay, and angiotensin converting enzyme 2 (ACE2) activity, NF-κB, RIG-I, MAD5, and IRF3 were measured using specific ELISA kits. Lr decreased viral load, ACE2, pro-inflammatory mediators, TLR2, TLR4, NF-κB, TLR3, TLR7, and TLR8 as well as TRIF and MyD88 expression in CSE and SARS-CoV-2 -exposed 16HBE cells. Otherwise, RIG-I, MAD5, IRF3, IFN-γ, and the MAVS expression were restored in 16HBE cells exposed to CSE and SARS-CoV-2 and treated with Lr. Lr induces antiviral signaling associated to IFN-γ secreting viral sensors and attenuates cytokine storm associated to NF-κB in bronchial epithelial cells, supporting its emerging role in prevention of COPD exacerbation.

Salvia hispanica L. (chia) seed ameliorates liver injury and oxidative stress by modulating NrF2 and NFκB expression in sucrose-rich diet-fed rats.

The aim of this study was to analyze the liver injury and oxidative stress in an experimental model of Metabolic Syndrome (MS) induced by chronic administration of a sucrose-rich diet (SRD) and to evaluate the effects of chia seed as a therapeutic strategy. Male Wistar rats were fed with a reference diet (RD) -6 months- or a SRD -3 months. Then, the latter group was randomly divided into two subgroups. One subgroup continued receiving the SRD for up to 6 months and the other was fed with a SRD where whole chia seed was incorporated as a source of dietary fat for the next 3 months (SRD+CHIA). The results showed that rats fed with a SRD for a long period of time developed dyslipidemia, hyperglycemia, hepatic lipid accumulation, liver injury, hepatic lipid peroxidation and oxidative stress. Hepatic NrF2 expression was significantly decreased. In addition, a significant increase in hepatic NFκB p65 expression and a positive correlation of this with plasma TNFα levels were found. The administration of chia seed for 3 months reversed dyslipidemia, hyperglycemia, lipid accumulation, liver injury, lipid peroxidation and oxidative stress. In the liver tissue, NrF2 expression was normalized and NFκB p65 expression was decreased, the latter was associated with a decrease in plasma TNFα levels. The present study showed new aspects of liver damage, lipid peroxidation and oxidative stress in dyslipidemic insulin resistant rats chronically fed with a sucrose-rich diet. However, we demonstrated new properties and molecular mechanisms associated with the beneficial anti-oxidant effects of chia seed consumption.

Distinct global DNA methylation and NF-κB expression profile of preimplantation biopsies from ideal and non-ideal kidneys.

BACKGROUND: Epigenetic mechanisms may affect the ideal and non-ideal kidneys selected for transplantation and their inflammatory gene expression profile differently and may contribute to poor clinical outcomes. OBJECTIVE: Study the Global DNA methylation and the expression profiles of the DNA methyltransferases (DNMTs) and nuclear factor kappa B (NF-κB) in preimplantation kidney biopsies from ideal and non-ideal kidneys (expanded criteria donor (ECD) and with KDPI > 85%). METHODS: In a sample consisting of 45 consecutive pre-implantation biopsies, global DNA methylation levels were detected by LINE-1 repeated elements using bisulfite pyrosequencing. DNMT gene expression was assessed by real-time quantitative polymerase chain reaction, and NF-κB protein expression by immunofluorescence. RESULTS: ECD kidneys displayed increased methylation levels in LINE-1, and DNMT1 and DNMT3B expression was upregulated when comparing ECD to standard criteria donor kidneys. Similarly, kidneys with KDPI > 85% exhibited increased LINE-1 methylation and DNMT1 upregulation when compared to a KDPI ≤ 85%. NF-κB protein expression levels were greatly increased in both types of non-ideal kidneys compared to ideal kidneys. Moreover, hypermethylation of LINE-1 was associated with cold ischemia time > 20 h and ECD kidney classification. CONCLUSIONS: This study shows that global DNA hypermethylation and high expression of NF-κB occurred in both types of non-ideal kidneys and were associated with prolonged cold ischemia time. Global DNA methylation can be a useful tool to assess non-ideal kidneys and hence, could be used to expand the pool of kidneys donors.

The microRNA-520a-3p inhibits invasion and metastasis by targeting NF-kappaB signaling pathway in non-small cell lung cancer.

PURPOSE: To identify the expression of miR-520a-3p and AKT1 in non-small cell lung cancer cells (NSCLC) and the mechanism in inhibiting cell invasion and metastasis by targeting NF-kappaB signaling pathway. METHODS: Bioinformatics analysis and dual luciferase reporter gene assay were used to predict and verify the targeting relationship between miR-520a-3p and AKT1. EdU assay was used to detect the proliferation of NSCLC cells. Flow cytometry detected the apoptosis of NSCLC cells. Transwell assay tested the invasion ability of NSCLC cells. qRT-PCR measured the expression of miR-520a-3p and AKT1 mRNA in NSCLC cells; while western blotting was adopted to detect the protein expressions of AKT1, Ki67, CyclinD1, Bax, Bcl-2, MMP-2, MMP-9, NF-kB p65, IkBs kinase (IKK), NF-kB inducing kinase (NIK). RESULTS: Bioinformatics analysis suggested that miR-520a-3p could target AKT1. miR-520a-3p could regulate the expression of AKT1 negatively. Compared to mimic-NC group, miR-520a-3p mimic group had increased expressions of miR-520a-3p and Bax, while decreased expressions of AKT1, Ki67, CyclinD1, Bcl-2, MMP-2, MMP-9, NF-kB p65, IKK and NIK, reduced cell proliferation, invasion, and increased cell apoptosis rate (all P < 0.05). Compared to inhibitor NC group, miR-520a-3p inhibitor group had decreased expressions of miR-520a-3p and Bax, but increased expressions of AKT1, Ki67, CyclinD1, Bcl-2, MMP-2, MMP-9, NF-kB p65, IKK and NIK, promoted cell proliferation, invasion, and suppressed cell apoptosis rate (all P < 0.05). CONCLUSION: Overexpression of miR-520a-3p can target and downregulate the expression of AKT1 to inhibit the invasion and metastasis of NSCLC via suppressing the activation of NF-kappaB signaling pathway.

Salmonella enterica serovar Typhi influences inflammation and autophagy in macrophages.

Salmonella enterica serovar Typhi (S. Typhi) is a human enteropathogen that can survive in macrophages and cause systemic infection. Autophagy and inflammation are two important immune responses of macrophages that contribute to the elimination of pathogens. However, Salmonella has derived many strategies to evade inflammation and autophagy. This study investigated inflammation-related NF-κB signaling pathways and autophagy in S. Typhi-infected macrophages. RNA-seq and quantitative real-time PCR indicated that mRNA levels of NF-κB signaling pathway and autophagy-related genes were dynamically influenced in S. Typhi-infected macrophages. Western blots revealed that S. Typhi activated the NF-κB signaling pathway and induced the expression of inhibitor protein IκBζ. In addition, S. Typhi enhanced autophagy during early stages of infection and may inhibit autophagy during late stages of infection. Thus, we propose that S. Typhi can influence the NF-κB signaling pathway and autophagy in macrophages.

Lactiplantibacillus plantarum Y15 alleviate type 2 diabetes in mice via modulating gut microbiota and regulating NF-κB and insulin signaling pathway.

Probiotics have been used for the treatment of chronic metabolic diseases, including type 2 diabetes (T2D). However, the mechanisms of antidiabetic effects are not well understood. The object of this study is to assess the antidiabetic effect of Lactiplantibacillus plantarum Y15 isolated from Chinese traditional dairy products in vivo. Results revealed that L. plantarum Y15 administration improved the biochemical indexes related to diabetes, reduced pro-inflammatory cytokines, L. plantarum Y15 administration reshaped the structure of gut microbiota, decreased the abundance of LPS-producing, and increased short-chain fatty acids (SCFAs)-producing bacteria, which subsequently reduce the levels of lipopolysaccharide (LPS) and pro-inflammatory cytokines. L. plantarum Y15 administration also regulated the expressions of the inflammation and insulin signaling pathway-related genes. These results suggest that L. plantarum Y15 may serve as a potential probiotic for developing food products to ameliorate T2D.

Perinatal and post-weaning exposure to an obesogenic diet promotes greater expression of nuclear factor-κB and tumor necrosis factor-α in white adipose tissue and hypothalamus of adult rats.

Aim: To analyze the effects of exposure to a high-fat diet during the perinatal period and after weaning on white adipose tissue accumulation and gene expression of TNF- α and NF- κB.Method: Wistar female rats were fed with high-fat (H) or control (C) diet during pregnancy and lactation. The offspring were allocated into four groups: Control Control (CC), offspring of mothers GC, fed a control diet after weaning; Control High-fat (CH), offspring of mothers GC, fed a hight-fat diet after weaning; High-fat Control (HC), offspring of mothers GH, fed with control diet after weaning; and High-fat High-fat (HH), offspring of mothers GH, fed a H diet after weaning.Results: HH and HC groups showed increased body weight compared to CC group and increases in caloric intake, larger amount of white adipose tissue and adipocyte size compared to CC and CH groups. The HH and CH groups showed higher NF-kB expression in white adipose tissue compared to the CC and HC groups, and the HH group also showed higher TNF- α expression. In the hypothalamus, the HH and HC groups exhibited higher TNF- α expression compared to the CC and CH groups.Conclusion: Perinatal and post-weaning exposure to the high-fat diet increases the amount of white adipose tissue, adipocyte size, and expression of the inflammatory genes TNF-α and NF-kB.

Systemic antioxidant and anti-inflammatory effects of yellow passion fruit bagasse extract during prostate cancer progression.

We evaluated the impact of yellow passion fruit (Passiflora edulis sp.) bagasse extract (PFBE) administration in systemic oxidative and inflammatory parameters in vivo, considering prostate cancer progression in transgenic mice (TRAMP). Piceatannol, scirpusin-B, dicaffeoylquinic acid, citric acid, and (+)-catechin were identified in PFBE, and the extract showed high in vitro antioxidant capacity. Some alterations in systemic parameters were verified during prostate cancer progression, as the increase in ALT and MDA levels, and SOD and GPx activities in the plasma. In the liver, higher MDA, TNF-α, and NF-κB levels, and GR and GPx activities were verified. Compared to their respective controls, the short- and long-term PFBE administration reduced MDA levels in the liver and plasma. The long-term treatment increased the catalase activity in the plasma, while the short-term treatment increased the hepatic SOD and catalase activities. Still, a reduction in hepatic TNF-α and NF-κB levels was verified after long-term treatment. PRACTICAL APPLICATIONS: Prostate cancer progression is associated with changes in systemic redox status and inflammation markers. Moreover, the intake of polyphenols with antioxidant properties, besides delaying prostate carcinogenesis, may improve the systemic antioxidant defenses and inflammatory response. In vitro studies pointed to a promising antioxidant and anti-inflammatory potential of yellow passion fruit bagasse. However, in vivo studies are scarce. Our results provided information about in vivo impacts of PFBE oral consumption on antioxidant defense and inflammation, indicating its potential as an adjuvant during the initial steps of prostate cancer.

The influence of the -94 Ins/Del ATTG polymorphism of NFkB on the anti-CCP antibody levels in patients with rheumatoid arthritis.

ABSTRACT: Rheumatoid arthritis (RA) is an autoimmune disease characterized by an inflammatory process that affects mainly synovial tissue in joints, and by the production of cyclic citrullinated peptides (anti-CCP) antibodies. In the inflammatory process the regulation of the nuclear factor kappa B (NFkB) transcription factor activation is a key point in the production of inflammatory cytokines. On the other hand, polymorphisms in several genes could contribute to the promotion of the inflammatory process observed in RA, and the association of the rs28362491 polymorphism in the NFkB gene with RA has been studied in different population. Therefore, it could be one of the interest targets to analyze their association with RA in a Mexican population.This is a case-control study to determine the influence of rs28362491 in the NFkB gene on RA and on clinical features of this disease, such as anti-CCP antibody levels, Disease Activity Score, and Health Assessment Questionnaire-Disability Index.The genotype of rs28362491 in the NFkB gene was determined in 140 RA patients and 135 healthy controls using the polymerase chain reaction-restriction fragment length polymorphism method with the enzyme PflMI. The following clinical variables were also determined: anti-CCP levels, Disease Activity Score, and Spanish version of the Health Assessment Questionnaire Disability-Index.Although no association of the polymorphism as a risk/protection factor with RA was found, the RA patients who carried the Ins/Ins genotype showed higher anti-CCP levels, while those with the Del/Del genotype showed higher Spanish version of the Health Assessment Questionnaire-Disability Index levels, compared to the other genotypes.The NFkB -94 Ins/Del ATTG (rs28362491) polymorphism is, therefore, associated with higher levels of anti-CCP antibodies, though no significant association as a risk or protection factor in RA cases was identified.