Expression Of Nuclear Factor Kappa Research Articles

Expression of nuclear factor kappa B components in the ovine maternal liver in early pregnancy periods.

There is a systemic immunological adaptation to maintaining tolerance towards the allogeneic fetus, and the liver participates in the adaptive immune tolerance during normal pregnancy. Nuclear factor kappa B (NF-κB) signalings contribute to immune regulation and liver homoeostasis. The objective of this study is to explore the effects of early pregnancy on expression of NF-κB components in the maternal liver in sheep. The maternal livers were sampled on Day 16 of the estrous cycle, and Days 13, 16, and 25 of gestation, and the expression of NF-κB components, including NF-κB1 (p50), NF-κB2 (p52), RelA (p65), RelB, and c-Rel, was detected by quantitative real-time polymerase chain reaction (PCR), Western blot analysis, and immunohistochemical analysis. Our data revealed that early pregnancy inhibited the expression of NF-κB1 and c-Rel, but the expression of NF-κB1 and c-Rel was increased during early pregnancy. However, early pregnancy enhanced the expression of NF-κB2, RelA, and RelB with the pregnancy progress. In conclusion, early pregnancy regulates the expression of NF-κB components in the maternal livers, which may contribute to maintaining maternal liver homeostasis and immune tolerance during early pregnancy in sheep.

Effects of Taurine against benzo[α]pyrene-Induced Cell Cycle Arrest and Reactive Oxygen Species-Mediated Nuclear Factor-Kappa B Apoptosis via Reduction of Mitochondrial Stress in A549 Cells

Taurine is a free amino acid that prevents reactive oxygen species (ROS) formation. ROS production is associated with oxidative stress, cell proliferation, apoptosis, inflammation, and DNA alterations in benzo[α]pyrene (BaP)-induced lung cells. Here, we assessed the effect of adding of 25 mM taurine on human pulmonary alveolar epithelial A549 cells treated with different concentrations of BaP. After culturing for 24 h, the cells were tested for biomarkers including cell viability, cellular morphology, Annexin V-FITC/propidium iodide, cell cycle regulation, ROS accumulation, mitochondrial membrane potential (MMP), and expression of related signaling genes and proteins. BaP induced cell cycle arrest and decreased cell viability in a dose-dependent manner. In addition, 50 μM BaP induced a 52.2% increase in ROS levels and inhibited MMP by up to 80%; however, taurine decreased BaP-induced ROS production by 19.5% and restored MMP. The expression of nuclear factor-kappa B (NF-κB), B-cell lymphoma-2 (BCL-2) homologous antagonist killer (Bak), BCL-2-associated X protein (Bax), and cytochrome c at both the mRNA and protein levels were increased, and the expression of BCL-2 and BCL-x1 was decreased by BaP treatment. Furthermore, BaP activated caspase-3/7 expression by up to 25%. However, taurine decreased the expression of NF-κB, Bak, Bax and cytochrome c levels, reduced caspase-3/7 activities, and increased the expression of BCL-2 and BCL-x1. Hence, taurine attenuates BaP-induced oxidative stress and mitochondrial dysfunction by inhibiting the NF-κB-mediated intrinsic apoptosis pathway in A549 cells. Taurine can be considered as a preventive molecule to prevent lung damage.

Anti-Oxidant and Anti-Inflammatory Effects of Lipopolysaccharide from Rhodobacter sphaeroides against Ethanol-Induced Liver and Kidney Toxicity in Experimental Rats.

This study aimed to investigate the protective effects of lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) against ethanol-induced hepatotoxicity and nephrotoxicity in experimental rats. The study involved an intact control group, LPS-RS group, two groups were given ethanol (3 and 5 g/kg/day) for 28 days, and two other groups (LPS-RS + 3 g/kg ethanol) and (LPS-RS + 5 g/kg ethanol) received a daily dose of LPS-RS (800 μg/kg) before ethanol. Ethanol significantly increased the expression of nuclear factor kappa B (NF-κB) and levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the liver tissue and decreased anti-oxidant enzymes. Hepcidin expression was downregulated in the liver, with increased serum levels of ferritin and iron. Prior-administration of LPS-RS alleviated the increase in oxidative stress and inflammatory markers, and preserved iron homeostasis markers. In the kidney, administration of ethanol caused significant increase in the expression of NF-κB and the levels of TNF-α and kidney injury markers; whereas LPS-RS + ethanol groups had significantly lower levels of those parameters. In conclusion; this study reports anti-oxidant, anti-inflammatory and iron homeostasis regulatory effects of the toll-like receptor 4 (TLR4) antagonist LPS-RS against ethanol induced toxicity in both the liver and the kidney of experimental rats.

Seabuckthorn Berries Extract Attenuates Pulmonary Vascular Hyperpermeability in Lipopolysaccharide-Induced Acute Lung Injury in Mice.

ObjectiveTo investigate the effect of seabuckthorn berries extract (SBE) on pulmonary vascular hyperpermeability in the mice model of acute lung injury (ALI) induced by lipopolysaccharide (LPS).MethodsSixty Kunming mice were allocated into 6 groups by a random number table, including control, LPS, dexamethasone (Dex, 1 mg/kg), and 120, 240 and 480 mg/kg SBE groups, 10 mice in each group. Except the control group, mice were pre-treated with Dex and SBE, respectively, for 7 days before LPS was intraperitoneally injected to induce ALI. Pulmonary vascular hyperpermeability was evaluated by histopathologic observation and transvascular leakage determination. Tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels in serum were measured using enzyme-linked immunosorbent assay. The expression of nuclear factor-kappa B (NF-κB) p65 in lung cells was determined by immunofluorescence analysis. The contents of cytoplasmic inhibitor of nuclear factor-κB kinase (IKK) and nuclear p65, as well as downstream proteins of E-selectin (CD62E) and intercellular adhesion molecule-1 (ICAM-1), were determined using Western blot analysis.ResultsHistopathological observation confirmed SBE treatment alleviated morphological lesion induced by LPS. Compared with the LPS group, 480 mg/kg SBE significantly decreased the water content of lung, Evans blue accumulation in lung tissue, and protein concentration and neutrophils count in bronchoalveolar lavage fluid (P<0.01); moreover, 480 mg/kg SBE significantly suppressed release of TNF-α and IL-6, and down-regulated expressions of IKK, nuclear p65, ICAM-1 and CD62E (P<0.01).ConclusionSBE maintained alveolar-capillary barrier integrity under endotoxin challenge in mice by suppressing the key factors in the pathogenesis of ALI.Electronic Supplementary MaterialSupplementary material (Appendix 1) is available in the online version of this article at 10.1007/s11655-021-3346-1.

Overexpressing long non-coding RNA OIP5-AS1 ameliorates sepsis-induced lung injury in a rat model via regulating the miR-128-3p/Sirtuin-1 pathway

ABSTRACT Sepsis, resulting from infections, is a systemic inflammatory response syndrome with a high fatality rate. The present study revolves around probing into the function and molecular mechanism of long non-coding RNA OIP5 antisense RNA 1 (lncRNA OIP5-AS1) in modulating acute lung injury (ALI) mediated by sepsis. Here, a sepsis model was constructed using cecal ligation and puncture (CLP) surgery in vivo. The alveolar macrophage cell line NR8383 and the alveolar type II cell line RLE-6TN were dealt with lipopolysaccharide (LPS) for in-vitro experiments. We discovered that OIP5-AS1 and Sirtuin1 (SIRT1) were markedly down-regulated in sepsis models elicited by CLP or LPS, while miR-128-3p experienced a dramatic up-regulation. OIP5-AS1 overexpression attenuated NR8383 and RLE-6TN cell apoptosis triggered by LPS and suppressed the expressions of nuclear factor kappa B (NF-κB), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in NR8383 and RLE-6TN cells, whereas miR-128-3p overexpression resulted in the opposite phenomenon. Moreover, OIP5-AS1 overexpression relieved lung edema, lung epithelial cell apoptosis, infiltration of myeloperoxidase (MPO)-labeled polymorphonuclear neutrophils (PMN), inflammatory responses triggered by CLP in vivo. Mechanistically, miR-128-3p, which targeted SIRT1, was hobbled by OIP5-AS1. All in all, OIP5-AS1 overexpression enhanced sepsis-induced ALI by modulating the miR-128-3p/SIRT1 pathway, which helps create new insights into sepsis treatment.

Proto-oncogene tyrosine-protein kinase SRC (Src) inhibition in microglia relieves neuroinflammation in neuropathic pain mouse models

ABSTRACT Chronic neuroinflammation is an important factor in the development of neuropathic pain (NP). Excess microglia activation releases a mass of pro-inflammatory cytokines during neuroinflammation process, leading to a constant painful irritation of the sensory nerve. Src belongs to a non-receptor tyrosine kinase associated with sarcoma, whereas the role of Src in neuropathic pain is controversial. We designed to testify the inflammation-regulatory role of Src in the lipopolysaccharide (LPS)-induced BV2 microglia line and the mouse model of neuropathic pain by partial sciatic nerve ligation (PNL). In BV2 microglia, Src expression was inhibited using a Src family kinase inhibitor PP2 after LPS induced inflammatory response. In vivo, the neuropathic pain in mice was induced by PNL surgery and then treated with PP2. The neuroinflammation level in vitro was detected by enzyme-linked immunosorbent assay (ELISA), immunofluorescence (IF), trans-well and Western blotting (WB) assays, in vivo was examined in PNL mice using immunohistochemistry (IHC) and IF. Finally, mechanical allodynia and thermal hyperalgesia assays were used to access the functional evaluation. Inhibition of Src was decreased microglial inflammation and migration after LPS stimuli. Mechanistically, the expression of nuclear factor kappa B (NF-κB) pathway decreased after Src inhibition. The data in vivo showed that the decrease expression of Src reduced neuroinflammation and the amount of microglia in spinal dorsal horn (SDH), the mechanical allodynia of mice thereby attenuated after Src inhibition. These results indicated that the inhibition of Src took a protective effect in neuropathic pain mouse models via reducing microglia-induced neuroinflammation.

Expressions of Nuclear Factor-kappa B and Peroxisome Proliferator-activated Receptor-Gamma Proportional with Clinical Staging of Nasopharyngeal Carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignancy induced by the mutation of the transcription factors nuclear factor-kappa B (NF-kB) and peroxisome proliferator-activated receptor-gamma (PPAR-gamma). There was no known of the study about the association and targeted therapy of NF-kB and PPAR-gamma-induced NPC. AIM: This study analyzed and compared the proportion of NF-kB and PPAR-gamma and its association with the clinical characteristic of various NPC patients. METHODS: This was a cross-sectional study and conducted in Adam Malik General Hospital. The samples were paraffin block tissue obtained from 58 NPC patients and underwent immunohistochemistry staining for NF-kB or PPAR-gamma overexpression in March–November 2018. Determination of overexpression was based on the immunoreactive score. The association of NF-kB or PPAR-gamma overexpression with the clinical characteristics of the patients was analyzed using Fisher’s exact test. RESULTS: This study showed a significant increase of NF-kB and PPAR-gamma (p &lt; 0.05). Male was found common than women (3.46:1) with non-keratinizing squamous cell carcinoma as the most common form of NPC (75.9%) and the 41–60 years old is the most common age (56.9%). Overexpression of NF-kB and PPAR-gamma was found mostly in T3-T4 (66.0%; 69.6%), N+ (92.5%; 91.3%), and clinical Stage IV (67.9%; 73.9%), respectively. CONCLUSION: The number of samples overexpressed was proportional to the clinical stage of NPC. This study provides an insight into the relationship of NF-kB and PPAR-gamma to NPC, suggesting their role in the development of malignancy.

Agarwood Alcohol Extract Protects against Gastric Ulcer by Inhibiting Oxidation and Inflammation.

Background Agarwood has been used for centuries, especially for treatment of gastrointestinal diseases. Earlier studies of our laboratory suggested that agarwood alcohol extracts (AAEs) provided gastric mucosal protection. This study aims to investigate the ameliorative effect of AAEs on ethanol-induced gastric ulcers and its mechanism. Methods Mice were given agarwood induced by the whole-tree agarwood-inducing technique alcohol extract (WTAAE, 0.71, 1.42, and 2.84 g/kg), wild agarwood induced by axe wounds alcohol extract (WAAE, 2.84 g/kg), and burning-chisel-drilling agarwood alcohol extract (FBAAE, 2.84 g/kg) orally, respectively. After 7 days' pretreatment with AAEs, the gastric ulcers were induced by absolute ethanol. The ulcer index, gastric histopathology, biochemical parameters, and inflammatory proteins were evaluated. Results Pharmacological results showed AAEs (1.42 and 2.84 g/kg) reduced the gastric occurrence and ulcer inhibition rates up to more than 60%. AAEs decreased the level of nitric oxide (NO) and increased glutathione (GSH) and superoxide dismutase (SOD) levels. Besides, AAEs decreased the levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6), but the interleukin-10 (IL-10) was upregulated. The expressions of nuclear factor kappa B (NF-κB) and phosphorylated protein 38 (p-P38) were inhibited. The effect of WTAAE was better than that of FBAAE and similar to that of WAAE at the dose of 2.84 g/kg. Conclusions These results demonstrate that agarwood alleviates the occurrence and development of gastric ulcers via inhibiting oxidation and inflammation.

Kaempferol protects rats with severe acute pancreatitis through regulating NF-κB and Keap1–Nrf2 signaling pathway

Kaempferol (KF) is an important natural anti-inflammatory flavonol. Acute pancreatitis (AP) is an inflammatory disorder, which in about 20% cases may develop into severe acute pancreatitis (SAP) with a high mortality rate. This research was to study the effects and mechanism of kaempferol on SAP. SAP was induced by sodium taurocholate. The level of cytokines was analyzed by enzyme-linked-immunosorbent serologic assay. The expression of nuclear factor kappa B (NF-κB) and Kelch-like ECH-associated protein 1–nuclear factor erythroid 2-related factor 2 (Keap1–Nrf2) proteins was analyzed by Western blot assay. Pathological changes in the pancreas were evaluated by hematoxylin and eosin staining. Kaempferol attenuated pancreatic injury in SAP rats, including reduction in inflammatory infiltration and necrosis. The level of serum amylase and lipase was also decreased in kaempferol-treated SAP rats. Kaempferol inhibited the expression of inflammatory mediators (nuclear factor-α, Interlukin-1β, and Interlukin-6), and alleviated the oxidative stress characterized by the decreased malondialdehyde (MDA) and increased superoxide dismutase (SOD) levels. Kaempferol decreased the expression of cleaved caspase 3 and anti-apoptotic protein Bcl-2, which indicated that kaempferol could inhibit apoptosis of pancreatic cells in SAP rats. Kaempferol treatment could decrease the expression of p-p65 and the amount of nuclear Nrf2 (Nu-Nrf2), which demonstrated that kaempferol inhibited the NF-κB activation and enhanced the Keap1–Nrf2 pathway. Our research indicated that kaempferol could attenuate the pancreatic injury of SAP by regulating NF-κB and Keap1–Nrf2 signaling pathway. Kaempferol could serve as a natural candidate for treating SAP.

Short-lived sensitization of cardiovascular outcomes of postpartum endotoxemia in preeclamptic rats: Role of medullary solitary tract neuroinflammation

Preeclampsia (PE) is a pregnancy-related disorder with serious maternal complications. Considering the increased importance of postpartum infection in maternal morbidity and mortality, we investigated whether preeclamptic maternal programming alters cardiovascular consequences of endotoxemia in rats and the role of cardiac and brainstem neuroinflammation in this interaction. Preeclampsia was induced by oral administration of L-NAME (50 mg/kg/day) for 7 days starting from day 14 of conception. Changes in blood pressure, heart rate, and cardiac autonomic function caused by lipopolysaccharide (LPS, 5 mg/kg i.v.) were assessed in mothers at 3 weeks (weaning time) and 9 weeks postnatally. Compared with respective non-PE counterparts, LPS treatment of weaning PE mothers caused significantly greater (i) falls in blood pressure, (ii) rises in heart rate and left ventricular contractility (dP/dtmax), (iii) reductions in time and frequency domain indices of heart rate variability and shifts in cardiac sympathovagal balance (low-frequency/high-frequency ratio, LF/HF) towards parasympathetic dominance, and (iv) attenuation of reflex bradycardic responses measured by the vasoactive method. The intensified LPS effects in weaning PE rats subsided after 9 weeks of delivery. Immunohistochemical studies showed increased protein expression of nuclear factor kappa B (NF-κB) in brainstem neuronal pools of the nucleus of the solitary tract (NTS), but not rostral ventrolateral medulla (RVLM), in endotoxic PE weaning rats compared with non-PE rats. Cardiac NF-κB expression was increased by LPS but this was similarly noted in PE and non-PE rats. Together, preeclamptic maternal programming elicits short-term exacerbation of endotoxic cardiovascular and autonomic derangements due possibly to exaggerated NTS neuroinflammatory insult.

Neuroprotective Effects of Chemerin on a Mouse Stroke Model: Behavioral and Molecular Dimensions.

The present study was conducted to investigate the effects of different doses of recombinant human Chemerin (rhChemerin) on brain damage, spatial memory, blood-brain barrier (BBB) disruption and cellular and molecular mechanisms in a mouse stroke model. The mouse stroke model was developed by blocking the middle cerebral artery for 1h and performing reperfusion for 23h. Immediately, one and three hours after the stroke, 200, 400 and 800ng/mouse of intranasal rhChemerin was administered. Neuronal and BBB damage, spatial memory and neurological performance were examined 24h after the stroke. Western blotting and immunofluorescence were utilized to determine the effects of rhChemerin on the expressions of nuclear factor kappa B (NF-κB), pro-inflammatory cytokines such as TNF-α and IL-1β, anti-inflammatory cytokines such as IL-10 and TGF-β and vascular endothelial growth factor (VEGF). Administering 400 and 800ng/mouse of rhChemerin in the mice immediately and one hour after ischemia minimized the infarct size, BBB opening, spatial memory and neurological impairment (P < 0.001). Furthermore, 800ng/mouse of rhChemerin significantly diminished terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive (apoptotic) cells, suppressed the expressions of NF-kB, TNF-α and IL-1β and upregulated IL-10 and VEGF in the cortex and hippocampus of the mice. The present findings showed that rhChemerin administered immediately and one hour after stroke alleviates neuronal and BBB injures and improves spatial memory. These effects of rhChemerin may be mediated by inhibiting inflammatory pathways and apoptotic machinery.

Effect of local ozone treatment on rats with anterior rectal resection and the possible mechanisms

BackgroundAnterior resection syndrome (ARS) is characterized by the diverse and interchangeable evacuatory symptoms that may occur following distal colorectal resection. We aimed to investigate the effect and potential mechanisms of ozone perfusion on rats with anterior rectal resection (ARR).Material and methodsAfter establishment of rat ARR model, 20, 40 and 80 ug/ml ozone was used to treat rats by enema administration. The pathological examination of intestinal tissue was detected using hematoxylin–eosin staining. The rate of loose stools, minimum threshold volume of abdominal withdrawal reflex (AWR) and Bristol grade were used to evaluate the degree of abnormal defecation function. Subsequently, the levels of oxidative stress- and inflammation-related markers, 5-hydroxytryptamine (5-HT), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the serum and intestinal tissue were determined with the corresponding kits. Meanwhile, the expression of nuclear factor kappa B (NF-κB) p65, transient receptor potential vanilloid (TRPV)1, TRPV4, iNOS and 5-HT receptor 3A (5-HTR3A) was determined with RT-qPCR and western blotting.ResultsOzone administration (20 and 40 ug/ml) significantly alleviated the pathological changes of intestinal tissue-induced by ARR, accompanied by the decreased loose stools rate, Bristol score and increased abdominal withdraw reflex. However, 80 ug/ml of ozone intervention played opposite roles in the aforementioned changes with 20 and 40 ug/ml of ozone. Additionally, remarkably elevated reactive oxygen species (ROS), malonaldehyde (MDA), superoxide dismutase (SOD), 5-HT, iNOS and NO levels were observed in the ozone-treated groups (20 and 40 ug/ml), while high dose of ozone drastically improved ROS, MDA, 5-HT, iNOS and NO levels but reduced the activity of SOD. Consistently, the contents of inflammatory factors were decreased after low and middle doses of ozone administration. However, high dose of ozone aggravated the inflammatory injury. Moreover, 20 and 40 ug/ml ozone upregulated TRPV1 and TRPV4 expression but downregulated 5-HTR3A expression, which was restored after 80 ug/ml of ozone intervention. Remarkably, the levels of NF-κB p65 and iNOS were dose-dependently enhanced following ozone treatment.ConclusionsTaken together, low concentration of ozone attenuated intestinal injury induced by ARR via balancing oxidative stress and inflammation, but high concentration of ozone exacerbated the intestinal injury, which might be related to the 5-HT and TRPV signaling.

Neuroprotective Effect of Ganoderma lucidum Polysaccharides in an Epileptic Rat Model

We have previously shown the antiepileptic effects of Ganoderma lucidum polysaccharides in in vitro studies; however, so far there is no such study reported in an in vivo model. In this study, the status epilepticus was induced in rats by kainic acid injection followed by G. lucidum polysaccharides treatment once a day for 7 days. Their epileptic behavior, electroencephalograph, along with the expression of caveolin-1, brain derived neurotrophic factor, nuclear factor kappa B, and hippocampal neuronal survival were assessed. Results showed that the epileptic behavior was improved significantly after G. lucidum polysaccharides treatments by a significant reduction of both the epileptic score and the duration of a heavy seizure attack while increasing both the epileptic latency and the time to heavy seizure attack. The epileptic electroencephalograph was ameliorated from previous sharp waves and frequent high amplitudes spikes to a group of scattering waves with lower frequency and small spikes. Furthermore, G. lucidum polysaccharides treatments enhanced the expression of caveolin-1, brain derived neurotrophic factor, and survivin, but decreased nuclear factor kappa B expression. These changes indicate that G. lucidum polysaccharides can alleviate epileptic seizure and this neuroprotective effect may be via increasing the expression of caveolin-1, brain derived neurotrophic factor, and survivin and decreasing the expression of nuclear factor kappa B in the hippocampal neurons.

High-Fat Diet-Induced Obesity Aggravates Food Allergy by Intestinal Barrier Destruction and Inflammation

Introduction: The increase in high-fat diet (HFD)-induced obesity and food allergy leads to an assumption that the 2 are related. This study aims to (1) systematic verification of HFD-induced obesity aggravates food allergy and (2) explore the correlation and molecular mechanisms of HFD-induced obesity promotes food allergy. Methods: Female BALB/c mice are divided into the control group (control), the ovalbumin (OVA)-sensitized group (OVA), the HFD-induced obesity group (HFD), and HFD-induced allergic obesity group (HFD + OVA). Results: In vivo data showed that HFD feed enhance clinical symptoms and intestinal mucosa villi shed on allergic mice. Moreover, we found that HFD and OVA irritation enhanced levels of mast cell degranulation and Th2 humoral response. Additionally, Western blot analysis showed the potentiation of peroxisome proliferator-activated receptor γ (PPAR γ) remarkably reduced on intestinal in HFD and OVA group, thereby inhibiting the expression of nuclear factor kappa B (NF-κB)/PPAR γ signal the phosphorylation of NF-κB P65. Conclusions: Overall, our results suggest that HFD-induced obesity is a potential risk factor for food allergy, which related to intestinal barrier destruction and inflammation through the PPAR γ/NF-κB signaling pathway.

Bioactivity-Guided Extract Optimization of Osmanthus fragrans var. aurantiacus Leaves and Anti-Inflammatory Activities of Phillyrin.

The aim of this study was to identify the optimal extraction conditions for leaves of Osmanthus fragrans var. aurantiacus. Inhibitory effects of various extracts on NO production were compared. Antioxidant evaluations for total phenol and flavonoid contents were carried out using various extracts of O. fragrans var. aurantiacus leaves obtained under optimal extraction conditions that showed the greatest effect on NO production. The optimal method for extracting O. fragrans var. aurantiacus leaves resulted in an extract named OP OFLE. OP OFLE showed DPPH and ABTS radical scavenging activities in a concentration-dependent manner. Phillyrin (PH) was isolated as a major compound from OP OFLE by HPLC/DAD analysis. OP OFLE and PH reduced inducible nitric oxide (iNOS) and cyclooxygenase (COX)-2 protein expression and downregulated proinflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in LPS-stimulated RAW 264.7 and HT-29 cells. To determine the signal pathway involved in the inhibition of NO production, a Western blot analysis was performed. Results showed that OP OFLE decreased phosphorylation of extracellular regulated kinase (pERK) 1/2 and the expression of nuclear factor-kappa B (NF-κB). Our results suggest that extracts of O. fragrans var. aurantiacus leaves and its major components have biological activities such as antioxidative and anti-inflammatory properties.

Inhibitory Effect of Poria cocos Polysaccharides on Proliferation, Migration, and Invasion of Lung Cancer Cells, A549

We have investigated the inhibitory effect of polysaccharides of Poria cocos on the proliferation, migration, and invasion of A549 lung cancer cells. The results showed that compared to the control group, the proliferation, migration, and invasion ability of all the treatment groups were inhibited, and the expression levels of ki-67 protein, matrix metalloproteinase-2, and matrix metalloproteinase-9 were also inhibited (P &lt; 0.05). Moreover, polysaccharides of P. cocos significantly inhibited the expression of nuclear factor-kappa B (NF-κB) signaling pathway related genes p-p65 and p-IκB (P &lt; 0.05). In conclusion, the mechanism of the inhibition of proliferation, migration, and invasion of lung cancer A549 cells by the polysaccharides of P. cocos may involve the inhibition of the NF-κB signaling pathway.

Vitamin D Supplementation: Oxidative Stress Modulation in a Mouse Model of Ovalbumin-Induced Acute Asthmatic Airway Inflammation.

Asthma oxidative stress disturbances seem to enable supplementary proinflammatory pathways, thus contributing to disease development and severity. The current study analyzed the impact of two types of oral vitamin D (VD) supplementation regimens on the redox balance using a murine model of acute ovalbumin-induced (OVA-induced) asthmatic inflammation. The experimental prevention group received a long-term daily dose of 50 µg/kg (total dose of 1300 µg/kg), whereas the rescue group underwent a short-term daily dose of 100 µg/kg (total dose of 400 µg/kg). The following oxidative stress parameters were analyzed in serum, bronchoalveolar lavage fluid (BALF) and lung tissue homogenate (LTH): total oxidative status, total antioxidant response, oxidative stress index, malondialdehyde and total thiols. Results showed that VD significantly reduced oxidative forces and increased the antioxidant capacity in the serum and LTH of treated mice. There was no statistically significant difference between the two types of VD supplementation. VD also exhibited an anti-inflammatory effect in all treated mice, reducing nitric oxide formation in serum and the expression of nuclear factor kappa B p65 in the lung. In conclusion, VD supplementation seems to exhibit a protective role in oxidative stress processes related to OVA-induced acute airway inflammation.

Inflammation as a Possible Trigger for Mitoxantrone-Induced Cardiotoxicity: An In Vivo Study in Adult and Infant Mice.

Mitoxantrone (MTX) is a pharmaceutical drug used in the treatment of several cancers and refractory multiple sclerosis (MS). Despite its therapeutic value, adverse effects may be severe, namely the frequently reported cardiotoxicity, whose mechanisms need further research. This work aimed to assess if inflammation or oxidative stress-related pathways participate in the cardiotoxicity of MTX, using the mouse as an animal model, at two different age periods (infant or adult mice) using two therapeutic relevant cumulative doses. Histopathology findings showed that MTX caused higher cardiac toxicity in adults. In MTX-treated adults, at the highest dose, noradrenaline cardiac levels decreased, whereas at the lowest cumulative dose, protein carbonylation increased and the expression of nuclear factor kappa B (NF-κB) p65 subunit and of M1 macrophage marker increased. Moreover, MTX-treated adult mice had enhanced expression of NF-κB p52 and tumour necrosis factor (TNF-α), while decreasing interleukin-6 (IL-6). Moreover, while catalase expression significantly increased in both adult and infant mice treated with the lowest MTX cumulative dose, the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glutathione peroxidase only significantly increased in infant animals. Nevertheless, the ratio of GAPDH to ATP synthase subunit beta decreased in adult animals. In conclusion, clinically relevant doses of MTX caused dissimilar responses in adult and infant mice, being that inflammation may be an important trigger to MTX-induced cardiotoxicity.

Thalidomide reduces glycerol‐induced acute kidney injury by inhibition of NF-κB, NLRP3 inflammasome, COX-2 and inflammatory cytokines

Acute kidney injury (AKI) is an important clinical complication of rhabdomyolysis. The inflammatory processes are involved in the pathogenesis of AKI induced by rhabdomyolysis. Thalidomide is an anti-inflammatory agent that has been used in the treatment of inflammatory disorders. The aim of this study was to investigate the therapeutic effect of thalidomide and its underlying mechanisms on a mouse model of rhabdomyolysis-induced AKI. Mice were injected with a single dose of glycerol (50%, 10 ml/kg, im) to induce AKI, and treated with thalidomide (40 and 80 mg/kg/day, orally) for 2 days. Renal tissue and blood samples were collected for histological and biochemical analysis. In thalidomide treated mice, blood urea nitrogen (BUN) (59.3 ± 19.6 vs. 223 ± 33 mg/dl), plasma creatinine (0.58 ± 0.3 vs. 1.28 ± 0.3 mg/dl), relative kidney weight (0.93 ± 0.13% vs. 1.22 ± 0.1%) and histopathological damage (1.5 ± 0.8 vs. 3.3 ± 1.1 score) were significantly lower as compared to the glycerol group. The results also showed that the levels of malondialdehyde (MDA) (0.13 ± 0.02 vs. 0.2 ± 0.01 µM/mg), myeloperoxidase (MPO) (0.1 ± 0.05 vs. 0.25 ± 0.02 U/mg) and the expression of nuclear factor kappa B (NF-κB) (1.7-fold), NLRP3 inflammasome (1.4-fold) and cyclooxygenase (COX)-2 (3-fold) in renal tissue were significantly lower in thalidomide treated group than those in the glycerol group. Thalidomide treatment resulted in lower renal pro-inflammatory cytokines tumor necrosis factor (TNF)-α (6.7 ± 0.8 vs. 12.3 ± 1.2 ng/ml), interleukin (IL)-1β (3.2 ± 0.5 vs. 5.1 ± 0.3 pg/mg), IL-6 (24.7 ± 2.4 vs. 33 ± 3 pg/mg) and transforming growth factor (TGF)-β1 (0.6 ± 0.17 vs. 1.56 ± 0.24 ng/ml) than those in the glycerol treated mice. In addition the levels of monocyte chemoattractant protein (MCP)-1 (9.5 ± 1 vs. 12.8 ± 1.1 pg/mg) and intercellular adhesion molecule (ICAM)-1 (22.8 ± 7.8 vs. 53.3 ± 5.5 pg/mg) were significantly lower in renal tissue of mice treated with thalidomide as compared to the glycerol treated mice. In conclusion these data revealed that thalidomide may be a potential therapeutic approach against rhabdomyolysis-induced AKI through inhibition of inflammatory responses.

Paeoniflorin attenuates the allergic contact dermatitis response via inhibiting the IFN-γ production and the NF-κB/IκBα signaling pathway in T lymphocytes

Paeoniflorin (PF) has been demonstrated to have an anti-allergic and anti-inflammatory effect in the treatment of allergic contact dermatitis (ACD). However, its clinical application is hampered by the lacking of comprehensive mechanical explanation. This research aimed to study the effect of PF on the proliferation, apoptosis and cytokines secretion as well as the expression of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways of T lymphocytes activation in vitro and in vivo. We found that PF depressed human T lymphocytes activation via inhibition ofinterferon-gamma (IFN-γ) production and NF-κB/IκBα and p38 MAPK signaling pathway in vitro, also PF could attenuate such ACD responses by inhibiting the production of IFN-γ and NF-κB/IκBα pathway in T lymphocytes of ACD mouse model, suggesting that PF might be useful for the treatment of T cell-mediated allergic inflammatory disorders such as ACD. This would make PF a promising T cell-targeted drug candidate for further study because of its immunosuppressive and anti-inflammatory effects.