Grape Seed Procyanidin Extract Reduces Arsenic- Induced Renal Inflammatory Injury in Male Mice

The aim of the present study is to evaluate the ability and mechanism by which grape seed procyanidin extract （GSPE） relieves arsenic trioxide （As2O3）-induced renal inflammatory injury. Therefore, male Kunming mice were treated with As2O3 and/or GSPE by gavage for 5 weeks. Mice were then sacrificed and inflammatory cytokines of kidneys were examined by ELISA, whereas the expression levels of molecules involved in the nuclear factor （NF）-KB signaling pathway were evaluated by both qRT-PCR and Western blot. Our results indicate that GSPE prevents As2O3-mediated renal inflammatory injury by inhibiting activation of the NF-KB signaling pathway and inflammatory cytokine production, while promoting expression of anti-inflammatory cytokines.

Ganoderma lucidum polysaccharide inhibits LPS-induced inflammatory injury to mammary epithelial cells

This study sought to investigate whether Ganoderma lucidum polysaccharide(GLP)has a protective effect on lipopolysaccharide(LPS)-induced inflammatory injury to mammary epithelial HC-11 cells and to characterize the mechanism involved.Cell viability was assessed using the cell counting kit 8(CCK-8)method,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and IL-1βlevels were measured by enzyme linked immunosorbent assay(ELISA),and IκBa,p65 NF-κB and STAT3 mRNA were determined using quantitative reverse transcription PCR(qRT-PCR),p65 and STAT3 protein expression were determined using Western blotting,respectively.GLP was shown to inhibit LPS-induced TNF-α,IL-6,and IL-1βproduction(P<0.01 or P<0.05),GLP was also shown to increase IκBαmRNA expression(P<0.01),decrease p65 and STAT3 mRNA expression(P<0.01 or P<0.05),and decrease p-p65,p65,p-STAT3,and STAT3 protein expression in breast epithelial cells(P<0.01 or P<0.05).The findings suggest that GLP inhibits nuclear factor kappa-B(NF-κB)and signal transducers and activators of transcription(STAT)signaling by preventing IκBαdegradation and p65 and STAT3 phosphorylation.This results in lower LPS-induced TNF-α,IL-6,and IL-1βproduction and prevents inflammatory cell injury.

Passive cigarette smoking induces inflammatory injury in human arterial walls

Background Epidemiological studies have shown that both active and passive cigarette smoking increase the risk of atherosclerosis. But very little is known about the biological processes induced by passive cigarette smoking that contribute to atherosclerosis. We observe the expression of a few of biological and inflammatory markers in human arterial walls in vitro which were treated with the second-hand smoke solution （sidestream whole, SSW）, and discuss the possible mechanism of inflammatory injury induced by second-hand smoke. Methods The biological markers （platelet endothelial cell adhesion molecule-I, PECAM-1; a-smooth muscle actin, a-SMA; collagen IV, Col IV） and inflammatory markers （vascular cell adhesion molecule-1, VCAM-1; monocyte chemoattractant protein-1, MCP-1 ; interleukin-8, IL-8） of human aortat wall were tested by immunofluorescence staining. The levels of MCP-1 and IL-8 mRNA expression were detected by reverse transcription-polymerase chain reaction （RT-PCR）. Results No distinct difference was observed between SSW and the control group on the expression of biological markers as assessed by the light microscope. But the inflammatory markers VCAM-1, MCP-1 and IL-8 on the subendothelial layer and smooth muscle cell layers, which are near the endothelium of arterial wall, were strongly stained in the SSW group compared with the control group. Their fluorescence intensities in the 1：40 SSW group （VCAM-1： 0.35±0.04, MCP-1： 0.34±0.05, IL-8： 0.37±0.05） and the 1：20 SSW group （VCAM-I： 0.40±0.04, MCP-1： 0.52±0.09, IL-8： 0.51±0.07） were significantly stronger than the control group （VCAM-1： 0.12±0.04, MCP-1： 0.06±0.02, IL-8： 0.24±0.03） by semi-quantitative analysis of immunofluorescence （P 〈0.001 vs control）. MCP-1 mRNA expression in the 1：40 SSW （0.15±0.04） and the 1：20 SSW （0.19±0.06） group was significantly higher than in the control group （0.09±0.03） （P 〈0.05, P 〈0.01 vs control）; IL-8 mRNA expression in the 1：40 SSW （0.64±0.12） and 1：20 SSW （0.72±0.13） groups was also significantly higher than that in the control group （0.49±0.13） （P 〈0.05, P 〈0.01 vs control） by RT-PCR. Conclusions It is implied that a second-hand smoke solution induces the inflammatory reaction of the arterial wall by release of inflammatory factors even though there is no distinct structural change on the arterial walls under light microscope, indicating that passive cigarette smoking is related to inflammatory injury in human arterial wall and could be closely related to the early inflammatory stage of atherosclerosis.

Long non-coding RNA Coro Marker regulates oxidized LDL-induced inflammatory injury via NF-κB/NLRP3 signaling pathway

Background Long noncoding RNAs(lnc RNAs) are considered to be important for the development and progression of atherosclerosis. The lnc RNA AC100865.1(referred to as Coro Marker) has been recognized a novel and specific biomarker of coronary artery disease. However, its underlying molecular mechanisms remain unclear.Objective: The aim of this study was to investigate the implication of Coro Marker in oxidized low-density lipoprotein(ox-LDL)-induced apoptosis and inflammation in THP-1 cells. The regulatory relationship between Coro Marker and the nuclear factor kappa B(NF-κB)/NOD-like receptor protein 3(NLRP3) pathway was also explored.Methods: THP-1 cells were stimulated with ox-LDL to induce inflammatory injury. The expression of Coro Marker was silenced by small interfering RNA. Cell apoptosis were assessed by flow cytometry. Inflammatory response was determined by detecting levels of inflammatory cytokines using quantitative real-time polymerase chain reaction(q RT-PCR) and enzyme-linked immunosorbent assay(ELISA). Furthermore, western blot was used to assess the expression of NF-κB/NLRP3 signaling pathway-related proteins. Results: Ox-LDL markedly induced cell injury by promoting cell apoptosis, oxidative stress, and inflammation. Meanwhile, the expression of Coro Marker was also up-regulated in ox-LDL-injured THP-1 cells. The knockdown of Coro Marker reduced apoptosis rate and significantly changed the expression levels of apoptosis-related genes(Bax and BCL-2). In addition, knockdown of Coro Marker relieved oxidative stress by significant changes in the level of malondialdehyde, superoxide dismutase, and reactive oxygen species, and attenuated inflammatory injury by inhibit the production of interleukin-1β(IL-1β), IL-6 and tumor necrosis factor alpha(TNF-α). Importantly, the suppression of Coro Marker decreased the expression of NF-κB/NLRP3 signaling pathway-related proteins, including p-NF-κB, p-Ik Bα and NLRP3.Conclusion: This study demonstrated that downregulation of Coro Marker alleviated ox-LDL-induced oxidative stress and inflammatory injury in THP-1 cells, possibly by modulating the NF-κB/NLRP3 signaling pathway.

Effects of realgar on stress proteins, inflammatory mediators, and complement in brain tissue and serum of rats with inflammatory brain injury

BACKGROUND：The Chinese herbal compound realgar exerts detoxification effects as an adjuvant. It is suggested that realgar exerts detoxification via the following pathways： in the pathological state, realgar corrects the oxidative stress state by increasing stress levels, activating some endogenous protective factors and antagonizing the excessive release of inflammatory factors, as well as inhibiting complement activation. OBJECTIVE： To observe the changes in stress proteins, inflammatory mediators, and complement in the brain tissue and serum of rats with inflammatory brain injury, which have been treated with the Chinese herbal compound Angong Niuhuang, and to compare the efficacy of Angong Niuhuang with that of realgar, to verify the mechanism of action of realgar. DESIGN, TIME AND SETTING： Randomized, controlled, cytological experiment, performed in the Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine in March 2006. MATERIALS： Thirty-six healthy, male, Sprague Dawley rats received 250 U/kg Bordetella pertussis via the common carotid artery within 15 seconds to induce inflammatory brain injury. Reagents and kits were as follows： Realgar and Angong Niuhuang powder （Foshan Second Pharmaceutical Factory, China）, Bordetella pertussis diagnostic antigen （National Institute for the Control of Pharmaceutical and Biological Products, China）, heat shock protein 70 （HSP70） enzyme-labeled immunosorbent assay （ELISA） kit （Stressgen, USA）, tumor necrosis factor-α （TNF-α） ELISA kit （Biosource, USA）, nitric oxide synthase （NOS） kit, Coomassie brilliant blue protein kit （Nanjing Jiancheng Bioengineering Co.,Ltd., China）, and complements C3 and C4 （Shanghai Kehua Dongling Diagnositic Products Co.,Ltd., China）. METHODS： Thirty-six rats were randomly and evenly divided into the following six groups： normal control, model, high-, middle-, and low-dose realgar-treated, and Angong Niuhuang-treated groups. At one hour prior to establishing the model, rats in the high-, middle-, and low-dose realgar-treated groups were administered 300, 150, and 75 mg/kg realgar, respectively; while rats in the Angong Niuhuang group received 1.5 g/kg Angong Niuhuang powder; In the model group, rats were administered Bordetalla pertussis only. MAIN OUTCOME MEASURES： Two hours after the administration of Bordetalla pertussis, the HSP70 level in the brain tissue and serum levels of interleukin-1β （IL-1β）, interleukin-6 （IL-6）, and TNF-α were determined by ELISA tests, hemooxygenase-1 （HO-1） activity in the brain tissue and serum was determined by dual-wavelength spectrophotometry, NOS and inducible nitric oxide synthase （iNOS） activities in the brain tissue were measured by the Bradford assay method, and serum levels of complement C3 and C4 were determined by immunoturbidimetry. RESULTS： In the high-dose realgar and Angong Niuhuang groups, the HSP70 level in the brain tissue of rats with inflammatory brain injury was increased significantly （P 〈 0.01）. In the realgar-treated groups, HO-1 activity in the brain tissue and serum was dose-dependently enhanced with increasing realgar doses. However, no significant difference existed between the realgar groups and the model group （P 〉 0.05）. In the Angong Niuhuang group, HO-1 activity in the brain tissue and serum was increased （P 〈 0.05）. In the realgar and Angong Niuhuang groups, serum levels of IL-1β, IL-6, and TNF-α were significantly decreased; the serum IL-1β level recovered to the normal level and serum levels of IL-6 and TNF-α dose-dependently decreased in the realgar groups. NOS activity in the brain tissue was lower in the high-dose realgar group than in the model group （P 〈 0.05）. iNOS activity was significantly lower in the middle- and high-dose realgar groups than in the model group （P 〈 0.01）. NOS and iNOS activities were significantly lower in the Angong Niuhuang group than in the model group （P 〈 0.01）. The serum C3 level was significantly decreased in the middle-dose realgar and Angong Niuhuang groups （P 〈 0.01）. CONCLUSION： At certain doses, realgar is able to correct the oxidative stress state, by inducing and activating endogenous protective factors, such as HSP70, and inhibiting the excessive release of inflammatory mediators, such as IL-1β, IL-6, and TNF-α. However, it remains unclear whether realgarinhibits the activation of C3 and C4.

The Three Main SCFAs Inhibit the Inflammatory Response of A549 Cells Induced by Acinetobacter baumannii

Objective: The objective is to explore the mechanism of inhibitory effect of three main SCFAs (acetate, propionate and butyrate) on inflammatory response of A549 cells. Methods: Human lung adenocarcinoma cells (A549 cells) were cultured, and were divided into normal control group (NC group), A. baumannii infection group (A. baumannii group), NF-κB inhibitor group (JSH group), A. baumannii infection + sodium acetate group (NaAc group), A. baumannii infection + sodium propionate group (NaPc group) and A. baumannii infection + sodium butyrate group (NaB group). Real-time quantitative PCR was used to detect the mRNA expression of NLRP3, Caspase-1, IL-1β, IL-6, and TGF-β in A549 cells. Western blotting assay was used to determine the expression of autophagy and “pyroptosis” related proteins of NRLP3, cleaved-Caspase-1 (P20), GSDMD (P30), LC-3 and Beclin-1. At the same time, the expression of NF-κB p65 protein in nucleus and cytoplasm of A549 cells was detected. The level of reactive oxygen species in A549 cells was detected by flow cytometry. Results: Compared with A. baumannii group, the mRNA expression of NLRP3, IL-1β and IL-6 in NaAc group, NaPc group and NaB group decreased significantly, the mRNA expression of Caspase-1 in NaPc group and NaB group decreased significantly, only the mRNA expression of TGF-β in NaB group increased significantly;LC3-II expression increased significantly in NaPc group and NaB group, only Beclin-1 expression increased and GSDMD (p30) expression decreased significantly in NaB group. All three kinds of SCFAs could significantly inhibit the expression of cleaved-Caspase-1 (p20) after A. baumannii infection, but there was no significant change in the protein expression of NLRP3. Compared with NC group, the production of reactive oxygen species in A. baumannii group increased significantly at 3 h after A. baumannii infection. Compared with A. baumannii group, NaB could significantly suppress the production of reactive oxygen species induced by A. baumannii. Compared with A. baumannii group, the expression of NF-κB p65 in nucleus was significantly decreased and the expression of NF-κB p65 in cytoplasm was significantly increased after 24 h pre-incubation with NaB, NaPc and NaAc, respectively. Conclusion: A. baumannii can induce inflammatory injury of pulmonary epithelial cells, and the three major SCFAs can inhibit the activation of NLRP3 inflammasome and the release of pro-inflammatory factors through NF-κB/ROS/NLRP3 pathway, which provides a new way for clinical prevention of severe inflammatory injury caused by A. baumannii infection.

Examining the properties and therapeutic potential of glial restricted precursors in spinal cord injury

In the aftermath of spinal cord injury,glial restricted precursors（GRPs） and immature astrocytes offer the potential to modulate the inflammatory environment of the injured spinal cord and promote host axon regeneration.Nevertheless clinical application of cellular therapy for the repair of spinal cord injury requires strict quality-assured protocols for large-scale production and preservation that necessitates long-term in vitro expansion.Importantly,such processes have the potential to alter the phenotypic and functional properties and thus therapeutic potential of these cells.Furthermore,clinical use of cellular therapies may be limited by the inflammatory microenvironment of the injured spinal cord,altering the phenotypic and functional properties of grafted cells.This report simulates the process of large-scale GRP production and demonstrates the permissive properties of GRP following long-term in vitro culture.Furthermore,we defined the phenotypic and functional properties of GRP in the presence of inflammatory factors,and call attention to the importance of the microenvironment of grafted cells,underscoring the importance of modulating the environment of the injured spinal cord.

The HMGB1 signaling pathway activates the inflammatory response in Schwann cells

Schwann cells are not only myelinating cells, but also function as immune cells and express numerous innate pattern recognition receptors, including the Toll-like receptors. Injury to peripheral nerves activates an inflammatory response in Schwann cells. However, it is unclear whether specific endogenous damage-associated molecular pattern molecules are involved in the inflammatory response following nerve injury. In the present study, we demonstrate that a key damage-associated molecular pattern molecule, high mobility group box 1（HMGB1）, is upregulated following rat sciatic nerve axotomy, and we show colocalization of the protein with Schwann cells. HMGB1 alone could not enhance expression of Toll-like receptors or the receptor for advanced glycation end products（RAGE）, but was able to facilitate migration of Schwann cells. When Schwann cells were treated with HMGB1 together with lipopolysaccharide, the expression levels of Toll-like receptors and RAGE, as well as inflammatory cytokines were upregulated. Our novel findings demonstrate that the HMGB1 pathway activates the inflammatory response in Schwann cells following peripheral nerve injury.

Tricky Presentation of Multisystem Inflammatory Syndrome in Children (MIS-C) with in Pediatric

Introduction: In emergence a COVID patient with multisystem inflammatory syndrome in children (MIS-C), associated with SARS-CoV-2, has shown increasing number among pediatric. Even the same presentation of Kawasaki disease we have to keep in mind MIS-C, in order to reach a consensus on this new disease in the future. Three variations of the disease patterns were reported: a group of children with increase in inflammatory activity and persistent fever, without criteria for Kawasaki disease, a second group with Kawasaki disease criteria, and a third group with shock, coronary aneurysms, severe cardiac dysfunction, and gastrointestinal symptoms. Classic Kawasaki disease is self-limited vasculitis which affects medium-sized vessels, almost occurred in children under five years old. Here, we bring a Saudi case, present to emergency department in Prince Sultan Military Medical City. Case report: 10 years old female, medically free, presented with abdominal pain, fever and skin rashes. Patient had history of COVID-19 infection 1 month before presentation. Initial investigations showed acute kidney injury with elevated inflammatory markers. Conclusion: Further evidence of the increase in the incidence of pediatric MIS-C, temporarily is associated with SARS-CoV-2. Physician should give more attentions to this new diagnosis with more fatal outcomes than Kawasaki cases.

NF-κB: A novel therapeutic pathway for gastroesophageal reflux disease?

Although gastroesophageal reflux disease(GERD),a common chronic disease in clinical practice,has been widely studied,its potential adverse impact on patients is still a significant clinical concern.It is necessary to understand the pathogenesis of the disease and choose appropriate treatment according to its mechanism.The pathogenesis of GERD is diverse and complex.As the traditional treatment methods are expensive and ineffective in alleviating symptoms in some patients,new treatment options need to be explored.Our previous study suggested that the activation of nuclear factor-kappa beta(NF-κB)in esophageal mucosa may be related to the injury of epithelial barrier function caused by reflux.Based on the literature and our previous study results,it is speculated that inhibition of NF-κB activation may block the insult of GERD on the esophageal mucosal barrier.NF-κB may play an important role in the development of GERD.This article reviews the pathogenesis of GERD and the relationship between NF-κB and GERD,in order to provide new strategies for the treatment of GERD.

Mangiferin alleviates renal infammatory injury in spontaneously hypertensive rats by inhibiting MCP-1/CCR2 signaling pathway

Objective: Hypertension is a low-grade infammation state of the disease and was easily complicated by kidneys’ infammatory response. Mangiferin(MGF), a pharmacologically active compound in various plants including Mangifera indica, has a strong anti-infammatory activity. However, the effects of MGF on renal infammatory injury in spontaneously hypertensive rats(SHRs) remain unclear. The purpose of this study was to investigate the protective effects and mechanisms of MGF on renal infammatory injury in SHRs.Methods: MGF was used in SHRs at the doses of 10, 20, 40 mg/kg/d for 8 weeks consecutively. The blood and urine were collected for assessment of renal function. Renal tissues were collected for histological,immunohistochemistry, ELISA, Western blot and real time reverse transcription PCR(RT-PCR) analysis.Results: The results showed that the levels of interleukin 6(IL-6), tumor necrosis factor-a(TNF-a), monocyte chemoattractant protein-1(MCP-1) and recombinant chemokine C-C-Motif receptor 2(CCR2) were increased in SHRs, meanwhile, the level of IL-10 was decreased in SHR. Treatment of MGF inhibited the expression of IL-6, TNF-a, MCP-1 and CCR2, and promoted the expression of IL-10. Furthermore, the content of blood urea nitrogen(BUN) and serum uric acid(SUA) was significantly increased in the model group, and treatment of MGF had no obvious effects on these parameters at all dose levels.Conclusion: Our study proved that the kidneys of SHRs had significant infammatory injury, and MGF had the protective effects on renal infammatory injury in SHRs;The protective mechanism may be mediated partly by the MCP-1/CCR2 signaling pathway. Thus, it is a potential new drug for the treatment of hypertension.

Ischemic preconditioning produces more powerful anti- inflammatory and cardioprotective effects than limb remote ischemic postconditioning in rats with myocardial ischemia-reperfusion injury

Background Both ischemic preconditioning （IPC） and limb remote ischemic postconditioning （LRIPOC） have been shown to possess significantly different cardioprotective effects against the myocardial ischemia reperfusion injury （IRI）, but no study has compared the anti-inflammatory effects of IPC and LRIPOC during myocardial IRI process. We hypothesized that IPC and LRIPOC would produce different anti-inflammatory effects in an in vivo rat model with myocardial IRI.

Hydrogen sulfide protects against high glucose-induced H9c2 cardiomyocyte injury and inflammatory response by inhibiting ROS-TLR4 pathway

Objective To investigate whether exogenous hydrogen sulfide（H2S）protects high glucose（HG）-inducedH9c2 cardiomyocyte injury and inflammation response by inhibiting reactive oxygen species（ROS）-Toll-like receptor 4（TLR4）pathway.Methods Cell counter kit-8（CCK-8）assay was used to measure the cell viability,