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An in vitro study was conducted using a model of reconstituted human corneal epithelial (SkinEthic™ HCE/Human Corneal Epithelium) to test the modulation of cytokines secretion activity of Pomanox® (PMX), a standardized commercial extract of pomegranate fruit characterized by high punicalagin α + β content. Cell viability and inhibition of the release of interleukin-8 (IL-8) was evaluated in four conditions: negative control, positive inflammatory control with lipopolysaccharide (LPS) from Escherichia coli, positive anti-inflammatory control (LPS plus dexamethasone), and LPS plus PMX after 24 h of culture. The mean (±standard error of mean (SEM)) IL-8 level was 48.7 ± 5.1 pg/mL in the PMX condition vs. 172.7 ± 19.3 and 26.6 ± 1.2 in the LPS from E. coli and negative control, respectively (p < 0.05) and 93.8 ± 8.7 pg/mL in LPS plus dexamethasone (p = 0.165). The percentages of inhibition of IL-8 release were 45.7% for LPS plus dexamethasone and 63.8% for LPS plus PMX. The percentage of cell viability (86%) was also higher for the LPS plus PMX condition. The present findings add evidence to the anti-inflammatory effect of a PMX in an in vitro model of reconstituted corneal epithelial cells.

Metal particles found in tissues around dental implants have been proposed to play a pathogenic role in peri-implantitis. Ultrasonic scaling has been suggested as a mechanism by which these particles can be inadvertently released into surrounding tissues. Furthermore, risk factors like diabetes can result in exacerbation of this inflammatory condition. The current study aimed to analyze metal particles released from titanium surfaces during ultrasonic scaling and their impact on pro-inflammatory cytokine production by human gingival fibroblasts.Metal particles generated from ultrasonic scaling of titanium discs using two different tips (metal and poly-etheretherketone tips) were characterized using scanning electron microscopy and elemental analysis. Endotoxin levels and Human gingival fibroblast viability, in the presence commercial and ultrasonically generated particles were determined. Fibroblasts, cultured in high or low glucose growth medium, were incubated with commercial titanium particles or ultrasonically generated particles in the presence or absence of interluekin-1β. Interleukin 6 and interleukin 8 production were then quantified using Enzyme linked immunosorbent assay.Analysis of particles after scaling of titanium discs showed significant levels of titanium particles. Commercial titanium particles and generated particles had no effect of fibroblast viability. Endotoxin levels of all particles were too low to stimulate HGF cells. IL-1β significantly stimulated IL-6 and IL-8 production. However, commercial, and generated particles generally had no significant effect on IL- 6 and IL-8 production.Our study concluded that particles generated during ultrasonic scaling had no significant effect on viability of HGF cells and cytokine production.

Intestinal enteritis is a main issue in crucian carp production which results in massive economic loss. Traditional antibiotics used for disease prevention of crucian carp (Carassius carassius) have been banned, thus an alternative approach needs to be identified. In this study, the bioactive peptide was evaluated as a diet supplement for preventing intestinal inflammation in crucian carp. Intestinal inflammation was induced by intrarectal administration of a 2,4,6-trinitrobenzene sulfonic acid (TNBS) solution. The fish samples were fed with different diets for 14 days. The disease activity index (DAI), which included, fish swimming, food intake, anal inflammation, body surface, and ascites was determined daily. Intestine segments were stained with haematoxylin and eosin (H.E.) for histopathological analysis. The expression of cytokines, including interleukin-1β (IL-1β), interleukin-8 (IL-8), tumor necrosis factor α (TNF-α), and myeloperoxidase (MPO) in crucian carp were determined. In TNBS-induced groups, the DAI scores were dramatically increased compared to the control group. The histopathological analysis showed that the damage of the fish intestine after the injection of TNBS. The relative expression levels of pro-inflammation cytokines (TNF-α, IL-1β, IL-8, MPO) were significantly increased compared to the control group on day 1. In the TNBS-induced group feed with a diet supplemented with bioactive peptide, the symptoms of intestinal inflammation were relieved on day 3 and the mRNA expression levels of pro-inflammation cytokines (TNF-α, IL-1β, IL-8, MPO) were reduced compared to day 1. On day 7, the fish samples enrofloxacin group and bioactive peptide group were recovered from TNBS-induced intestinal inflammation. This study showed that the fish diet supplemented with bioactive peptide could help to prevent and recover from intestinal inflammation. Thus, the bioactive peptide can be used as a replacement for antibiotics to prevent disease in aquaculture production.

There have been limited studies focused on validation of swine microRNAs (miRNA) with mRNA targets. The objective of this study was to validate a defined set of targets using artificial miRNA mimics transfected into cell lines to confirm specific targets of endogenous miRNAs after administration of Escherichia coli lipopolysaccharide (LPS). Sixteen hours after mimic transfection of 3D4/21 cell lines, the cells were stimulated with 1 μg/ml LPS or phosphate-buffered saline (PBS). The cells were harvested and collected at 0, 1, 3, and 8 h post administration. The selected genes DAD1, IL8, and ESR, which are involved in known pathways of inflammation. and are predicted or validated human targets of either miR-146a, let-7a, or miR-22-3p. These were then evaluated by quantitative real-time-PCR (qRT-PCR) to verify microRNA-mRNA interaction in swine. Using the ROX reference dye, mRNA changes in expression were assessed using the comparative CT Method (ΔΔCT method) for normalization against the PBS control group. DAD1 and ESR1 were negatively regulated by miR-22-3p and miR-146a-5p, respectively in 3D4/21 cells after LPS stimulation. However, miR-146a-5p may play an indirect positive regulatory role of both DAD1 and IL8 mRNA expression. Furthermore, we found an inverse relationship between LPS stimulation compared with the let-7a-5p overexpression with DAD1. Our inflammation study provides new evidence on the roles and predicted targets of miR-146a, let-7a, and miR-22-3p in swine.

Excessive dietary carbohydrate commonly impairs the functions of liver and intestine in carnivorous fish. In the present study, a 10-week feeding trial was carried out to explore the regulation of biotin on the hepatic and intestinal inflammation and apoptosis in turbot (Scophthalmus maximus L.) fed with high carbohydrate diets. Three isonitrogenous and isolipidic experimental diets were designed as follows: the CC diet with 18.6% of carbohydrate and 0.04 mg/kg of biotin, the HC diet with 26.9% of carbohydrate and 0.05 mg/kg of biotin, and the HCB diet with 26.9% of carbohydrate and 1.62 mg/kg of biotin. Results showed that high dietary carbohydrate (HC diet) impaired the morphology of liver and intestine, however, inclusion of dietary biotin (HCB diet) normalized their morphology. Inflammation-related gene expression of nuclear factor κB p65 (nf-κb p65), tumor necrosis factor α (tnf-α), interleukin-1β (il-1β), il-6 and il-8, and the protein expression of NF-κB p65 in the liver and intestine were significantly up-regulated in the HC group compared to those in the CC group (P 0.05), the HCB diet decreased their expression compared to the HC group (P 0.05). The gene expression of il-10 and transforming growth factor-β (tgf-β) in the liver and intestine were significantly decreased in the HC group compared to the CC group (P 0.05), and inclusion of dietary biotin increased the il-10 and tgf-β expression in the liver and intestine (P 0.05). Moreover, compared to the CC group, the HC group had a stronger degree of DNA fragmentation and more TUNEL-positive cells in the liver and intestine, and the HCB group had a slighter degree of DNA fragmentation and fewer TUNEL-positive cells compared to the HC group. Meanwhile, the gene expression of B-cell lymphoma protein-2-associated X protein (bax) and executor apoptosis-related cysteine peptidase 3 (caspase-3) were significantly up-regulated and the gene expression of B-cell lymphoma-2 (bcl-2) was significantly down-regulated both in the liver and intestine in the HC group compared with those in the CC group (P 0.05). Inclusion of dietary biotin significantly decreased the bax and caspase-3 mRNA levels and increased bcl-2 mRNA level in the liver and intestine (P 0.05). In conclusion, high dietary carbohydrate (26.9% vs 18.6%) induced inflammation and apoptosis in liver and intestine. Supplementation of biotin (1.62 mg/kg vs 0.05 mg/kg) in diet can alleviate the high-dietary-carbohydrate-induced hepatic and intestinal inflammation as well as inhibit apoptosis in turbot. The present study provides basic data for the application of biotin into feed, especially the high-carbohydrate feed for turbot.

Background In current intensive care treatment, there are patients with severe burns who cannot be saved due to progressive organ failure. Further investigation of the pathogenesis of severe burns is needed to improve the mortality rate. In burns, inflammatory cytokines form a network that leads to an inflammatory response. Adipocytes secrete physiologically active substances (adipokines). The roles of adipokines have not been completely clarified in burn patients. This study aimed to determine the relation between serial changes of adipokines and clinical course in severely burned patients. Methods This was a single-center, retrospective, observational study. Patients’ blood samples were collected on the day of injury and around 1 week later. Adipokines (adiponectin, angiotensinogen, chemerin, CXCL-12/SDF-1, leptin, resistin, vaspin, visfatin), various inflammatory cytokines, syndecan-1 and C1 esterase inhibitor were measured. Results Thirty-eight patients were included. Resistin levels were significantly higher in the non-survivors versus survivors on Day 1 after burn injury. Hierarchical clustering analysis showed common clusters on Day 1 and at 1 Week after burn injury (resistin, IL-6, IL-8, IL10 and MCP-1). The correlation coefficient of resistin to SOFA score at 1 Week was significant. Logistic regression analysis showed a significant relation of resistin levels on Day 1 with prognosis; the area under the ROC curve for resistin was 0.801. Conclusions In the acute phase of burns, resistin was associated with other pro-inflammatory cytokines and was related to the severity and prognosis of major burns.

Salmonella enterica (SE) is a major foodborne bacterial pathogen in the United States, commonly found as the normal flora of various animals that is attributed to causing at least 1.2 million infections annually. Poultry plays a major role in disseminating SE through direct contact with live animals and consumption of contaminated products. Vaccinating poultry against SE is a sustainable approach that can reduce SE in the host, preventing future infections in humans. An intracellular autolytic SE serovar Typhimurium vaccine (STLT2

α1-Antitrypsin (AAT), a serine protease inhibitor, is the third most abundant protein in plasma. Although the best-known function of AAT is irreversible inhibition of elastase, AAT is an acute-phase reactant and is increasingly recognized to have a panoply of other functions, including as an anti-inflammatory mediator and a host-protective molecule against various pathogens. Although a canonical receptor for AAT has not been identified, AAT can be internalized into the cytoplasm and is known to affect gene regulation. Because AAT has anti-inflammatory properties, we examined whether AAT binds the cytoplasmic glucocorticoid receptor (GR) in human macrophages. We report the finding that AAT binds to GR using several approaches, including coimmunoprecipitation, mass spectrometry, and microscale thermophoresis. We also performed in silico molecular modeling and found that binding between AAT and GR has a plausible stereochemical basis. The significance of this interaction in macrophages is evinced by AAT inhibition of LPS-induced NF-κB activation and IL-8 production as well as AAT induction of angiopoietin-like 4 protein, which are, in part, dependent on GR. Furthermore, this AAT–GR interaction contributes to a host-protective role against mycobacteria in macrophages. In summary, this study identifies a new mechanism for the gene regulation, anti-inflammatory, and host-defense properties of AAT.

Cytokines in wound fluid are used as surrogates for wound healing in clinical research. The current methods used to collect and process wound fluid are noninvasive but not optimal. The aim of this prospective study was to evaluate a method (NovaSwab) by which wound fluid is collected by a surface swab and eluted in a physiological buffer for subsequent cytokine analysis. Wound fluid from 12 patients with leg ulcers was assessed by NovaSwab at the start (Day 0) and at the end of a 23-h collection period of wound fluid retained by foam oblates beneath an occlusive film dressing (Day 1). GM-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8, PDGF-AA, TNF-alpha and VEGF levels were measured by multiplex and electrochemiluminescence assays. IL-1 alpha (2.4x), IL-1 beta (2.0x) and IL-8 (1.8x) levels increased from Day 0 to Day 1 as detected by NovaSwab, indicating local production of these polypeptides in the wounds. On Day 1, the NovaSwab method yielded higher levels of IL-1 alpha (4.0x), IL-1 beta (2.7x) and IL-6 (2.7x), and 35% lower levels of VEGF than those in wound fluid accumulated for 23 h in foam oblates (on average, 5 ml of wound fluid). In vitro experiments showed that the investigated cytokines in cell-free wound fluid were recovered in a quantitative manner by the NovaSwab method. We conclude that the method presented here is a promising research tool to study the kinetics of soluble cytokines over the course of wound healing. More studies are needed to determine the interobserver variation and reproducibility of the NovaSwab method.

Cancer progression is associated with significant cachexia-induced weight loss and stomatitis. Pentoxifylline (PTX) is a drug shown to have beneficial anti-inflammatory effects in cancer patients, mainly through anti-TNFα mechanisms. This study determined the PTX effects and mode of action on weight-loss, stomatitis, and survival in colon cancer patients treated with chemotherapy, examining the kinetics of tumor markers and cytokine levels.Forty patients with metastatic colon cancer receiving chemotherapy, were randomized in this study. Seventeen patients were assigned to the treatment group - 8 received a full PTX dose (400 mg TID) and 9 a reduced dose (200 mg TID). Results were compared to 23 untreated, control patients. Blood analysis of tumor markers (CEA and TPS), inflammatory cytokines (IL-1β, IL-6, IL-8, TNFα, TNF-R), CRP and sIL-2R, were performed. Additionally, clinical parameters were assessed.Patients treated with PTX (full/reduced doses), gained significant weight, and experienced a reduction in stomatitis, resulting in multiple beneficial effects, including improved life quality. Significant reductions in CRP, sIL-2R, and inflammatory cytokine levels, correlated to increases in weight and a reduction in stomatitis. A similar pattern was observed in tumor marker levels, where decreasing levels were correlated with weight gain and reduction in inflammatory cytokine levels.Colon cancer patients receiving PTX with chemotherapy, experienced weight gain and reduced stomatitis occurrence. Beneficial PTX effects were correlated to significant decreases in patient inflammatory cytokines and tumor marker levels, probably due to PTX mode of action.

Anti- and proinflammatory cytokines and plasma high-sensitivity C-reactive protein (hs-CRP) are used to assess inflammatory stress response (ISR) following surgery. However, the serum IL-18 (interleukin-18) cytokine values versus numeric rating scale (NRS) pain score and number of analgesic doses (NAD) postoperatively are unknown.Blood levels of six interleukins (IL-18, IL-1ra, IL-6, IL-10, IL-1β, and IL-8) and hs-CRP were measured at three time points; before operation (PRE), immediately after operation (POP1), and six hours after operation (POP2) in 114 patients with cholelithiasis.Following surgery, the blood levels of hs-CRP and IL-1ra, IL-6, IL-10, and IL-1β cytokines had a trend for increase (p0.001 and p=0.014, respectively). The serum IL-18 concentrations inversely correlated to NRS and NAD during the first 24 h postoperatively.The correlation of IL-18 levels to NRS and NAD values supports the hypothesis that ISR and pain are related.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammation of the mucosa of the nose and paranasal sinuses with the presence of polyps, affecting between 2.7% and 4.4% of the population. Cytokine analysis has become important in research on inflammatory mechanisms in CRSwNP. Therefore, our aim is to investigate the complex appearance, relative distribution, and interlinks of IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, and Ki-67 in CRSwNP. Methods: Samples of nasal polyps were obtained from 19 patients with previously diagnosed CRSwNP and the recurrence of polyps after previous surgeries. The control group consisted of samples from 17 otherwise healthy individuals with isolated nasal septum deviations. Tissues were stained for previously mentioned cytokines and Ki-67 immunohistochemically. Results: Polyp samples showed an increased presence of cytokines in subepithelial connective tissue and a decreased appearance in epithelium when compared to controls. There were several very strong, strong, and moderate correlations among factors. Conclusions: IL-6 strongly correlates with other cytokines as well as with the proliferation marker Ki-67, which suggests significant stimulation of this regulatory cytokine and its possible involvement in the pathogenesis of recurrent nasal polyps. IL-4, IL-7, IL-10, and IL-12 correlate with Ki-67, which suggests the possible involvement of these cytokines in tissue cell proliferation in the case of recurrent nasal polyps.

Gouty arthritis (GA) is mainly caused by the precipitation of monosodium urate (MSU) crystals in the joint. Recently, different regulatory roles of microRNAs (miRNAs) in arthritis have been widely verified. Nevertheless, the specific function of microRNA-486-5p (miR-486-5p) in GA is still unclear. GA cell models

Purpose The present study aims to investigate the acute response of potential exercise-sensitive biomarkers in capillary plasma to an acute incremental running test. In a second step, their concentration was compared to the changes in the venous serum. Methods Thirty-seven active young female and male adults completed a VO2max ramp test on a treadmill. Before and after exercise, capillary blood from the earlobe and venous blood were taken and synchronized. Concentrations of Interleukin- (IL-) 1β, IL-1ra, IL-6, IL-8, IL-17A, Interferon (IFN)-y, CC-chemokine ligand (CCL)-2, Matrix metallopeptidase (MMP)-9, Secreted protein acidic and rich in cysteine (SPARC), Cluster of differentiation (CD)163, S100 Ca2+ -binding protein (S100) A8, S100A9, S100B, Brain-derived neurotrophic factor (BDNF), and Myeloperoxidase (MPO) were determined by magnetic bead-based multiplex assay. Results Capillary plasma concentrations of IL-1β, IL-6, IL-8, IL-17A, IFN-y, CCL-2, MMP-9, SPARC, CD163, S100A9, S100B, and BDNF increased after exercise (p Conclusion As in the venous serum, there was an increase in most markers in the capillary plasma. However, acceptable to low associations can be found in the concentration levels of these proteins between the compartments. Thus, this source of blood sampling could find some biomarker applications in sports practice.

The pro-inflammatory factor interleukin-8 (IL-8) is related to poor prognosis in hepatocellular carcinoma (HCC) patients. Interleukin-8 enhanced HCC invasion by upregulating Snail and Twist1, whether this modulation relies on microRNAs (miR) is unclear. In this study, hsa-miR-370-3p was screened as candidate miRNA targeting Snail and Twist1, and its expression was downregulated by IL-8. Luciferase assays and RNA electrophoretic mobility shift assays were used to evaluate the interaction between miR-370-3p and targeted mRNAs. Coimmunoprecipitation, luciferase, and ChIP assays were undertaken to investigate the mechanisms underlying IL-8-mediated modification of miR-370-3p. Gain- and loss-of-function studies, Transwell assays, and a xenograft nude mouse model were used to investigate pro- and antitumor activities. Interleukin-8 and miR-370-3p levels were analyzed for clinical relevance in HCC patients. Our results showed that HCC patients with high levels of IL-8 experienced more metastasis and shorter survival. Interleukin-8 induced epithelial-mesenchymal transition and promoted liver cancer cell migration, invasion, and metastasis both in vitro and in vivo. MicroRNA-370-3p interacted with its cognate mRNA within the 3'-UTR regions of Twist1 and Snail mRNA directly and specifically and attenuated IL-8 protumoral effects on liver cancer cells. Interleukin-8 negatively modulated miR-370-3p through signal transducer and activator of transcription 3 (STAT3) activation by recruiting histone deacetylase 1 (HDAC1) to miR-370-3p promoter. The STAT3 and HDAC antagonists inhibited liver cancer cell migration and invasion. Patients with high miR-370-3p and low IL-8 levels had longer overall survival. In conclusion, our study elucidated a novel axis IL-8/STAT3/miR-370-3p/Twist1 and Snail relying on HDAC1 recruitment, which showed both diagnostic and therapeutic potentials of miR-370-3p in HCC metastasis.

Objective. To systematically assess effectiveness and safety of Bifidobacterium quadruple viable bacteria combined with mesalamine against ulcerative colitis (UC) in the Asian population. Methods. An electronic search was conducted in PubMed, Embase, Cochrane Library, CNKI, VIP, and Wanfang databases for a random collection of controlled trials of Bifidobacterium quadruple viable bacteria combined with mesalamine against UC. Following data screening and extraction, a Cochrane risk assessment tool was adopted to evaluate the quality of the included studies, and RevMan 5.3 and Stata/SE 15.1 software were used for meta-analysis. Results.Nineteen articles which enrolled 1,707 subjects were included ultimately in this study. The experimental group performed better than the control group in improving the Mayo score ( MD = − 1.94 , 95% CI = − 2.69 , − 1.19 , P < 0.00001 ), increasing the total clinical efficiency ( OR = 5.10 , 95% CI (3.53, 7.38), P < 0.00001 ), reducing the levels of IL-8 ( SMD = − 1.79 , 95% CI (-2.36, -1.12), P < 0.00001 ), increasing the levels of IL-4 ( SMD = 1.00 , 95% CI (0.60, 1.41), P < 0.00001 ), and reducing the levels of hsCRP ( MD = − 3.26 , 95% CI (-4.28, -2.25), P < 0.00001 ), TNF-α ( MD = − 7.11 , 95% CI (-9.23, -5.00), P < 0.00001 ), ox-LDL ( MD = − 14.46 , 95% CI (-17.20, -11.72), P < 0.00001 ), and LPO ( MD = − 3.55 , 95% CI (-4.70, -2.39), P < 0.0001 ) as well as increasing SOD level ( SMD = 1.68 , 95% CI (1.02, 2.35), P < 0.00001 ), and adverse reactions were substantially less than that of control ( OR = 0.43 , 95% CI = 0.28 , 0.66 , P = 0.0001 ). Conclusion. In conclusion, the current meta-analysis shows that Bifidobacterium quadruple viable bacterium combined with mesalamine has a satisfactory effect in the treatment of UC in China, and its safety is better than that of mesalamine or Bifidobacterium quadruple viable bacteria alone. However, randomized controlled trials with standardized designs and large sample sizes are still needed for further validation.

INTRODUCTION: Organs procured following brain stem death (BSD) are the main source of organ grafts for transplantation. However, BSD is associated with inflammatory responses that may damage the organ and affect both the quantity and quality of organs available for transplant. Therefore, we aimed to investigate plasma and bronchoalveolar lavage (BAL) pro-inflammatory cytokine profiles and cardiovascular physiology in a clinically relevant 6-hour ovine model of BSD. METHODS: Twelve healthy female sheep (37‒42 Kg) were anaesthetized and mechanically ventilated prior to undergoing BSD induction and then monitored for 6 hours. Plasma and BAL endothelin-1 and cytokines (IL-1β, 6, 8 and tumour necrosis factor alpha (TNF-α)) were assessed by ELISA. Differential white blood cell counts were performed. Cardiac function during BSD was also examined using echocardiography, and cardiac biomarkers (A-type natriuretic peptide and troponin I were measured in plasma. RESULTS: Plasma concentrations big ET-1, IL-6, IL-8, TNF-α and BAL IL-8 were significantly (p < 0.01) increased over baseline at 6 hours post-BSD. Increased numbers of neutrophils were observed in the whole blood (3.1×109 cells/L [95% confidence interval (CI) 2.06 - 4.14] vs. 6×109 cells/L [95%CI 3.92 - 7.97]; p < 0.01) and BAL (4.5×109 cells/L [95%CI 0.41 - 9.41] vs. 26 [95%CI 12.29 - 39.80]; p=0.03) after 6 hours of BSD induction vs baseline. A significant increase in ANP production (20.28 pM [95%CI 16.18 - 24.37] vs. 78.68 pM [95%CI 53.16 - 104.21];p < 0.0001) and cTnI release (0.039 ng/mL vs. 4.26 [95%CI 2.69 - 5.83] ng/mL; p < 0.0001), associated with a significant reduction in heart contractile function, were observed between baseline and 6 hours. CONCLUSIONS: BSD induced systemic pro-inflammatory responses, characterized by increased neutrophil infiltration and cytokine production in the circulation and BAL fluid, and associated with reduced heart contractile function in ovine model of BSD.

BACKGROUND AND OBJECTIVES: Systemic sclerosis (SSc) is an autoinmune disease that can affect several organs and its mortality is fundamentally related to its pulmonary involvement. There are some cytokines with high serum levels of patients with SSc. Our goal is to determine the role of CXCL4, CXCL8 and GDF15 in the physiopathology of SSc and whether they can be considered organic damage biomarkers. PATIENTS AND METHODS: Observational case-control study of SSc patients (ACR/EULAR 2013 criteria). Demographic, clinical, analytical, activity, severity, health perception, and disability variables were collected. Moreover, Videocapillaroscopy, Echocardiography and Respiratory Function Test were made. Serum levels of CXCL4, CXCL8 and GDF15 were measured both in SSc patients and in healthy controls. RESULTS: A total of 42 patients were included (95.4% women), with an average age of 59.2 years and a median of 4 years from diagnosis. We also included 42 healthy controls. We found significantly higher levels of GDF15 in SSc patients than in controls (p

In cancer patients, an interleukin (IL)-8 gene variant that leads to higher production of IL-8, is associated with lower risk of depressive symptoms. In non-cancer adults, higher levels of IL-8 correlate with lower severity of depressive symptoms, decreased risk of suicide, and improved treatment response in females, but not males. This study evaluates the prospective association between circulating levels IL-8 and incident and recurrent major depressive disorder in breast cancer survivors.In this single site, prospective cohort study with protocol modification extending follow-up from 24- to 32 months, recruitment occurred between September 2013 and January 2018, and follow-up was completed February 2021. Participants were identified from a Kaiser Permanente of Southern California health plan-based sample of 219 breast cancer survivors, who were two or more years since diagnosis of early stage breast cancer (TNM 0-II), aged 55 to 85 years, with no major depression or health events in last year. Circulating levels of IL-8 were obtained at enrollment. Primary outcome was time to incident or recurrent major depressive disorder as diagnosed by interview and DSM-5 criteria.Among 219 participants (mean age, 70 years; 100% female; 16 [7.3%] Asian, 42 [19.2%] Black, 161 [73.5%] White), 84% completed 24 months follow-up. After protocol modification, 59% completed 32 months follow-up. Median follow-up was 28.5 months. The primary endpoint occurred in 27 participants (12.4%, 5.7 events /100 person years; 95% CI 2.7 - 8.8). Higher IL-8 was associated with lower risk of incident and recurrent depression (hazard ratio, HR, 0.52, 95% CI 0.26 - 1.05). Among those with levels of IL-8 in the highest quartile, the primary endpoint occurred in 2 participants (3.6%; 1.6 events/100 person years; 95% CI 1.3 - 1.9), as compared to 25 participants in the pooled lower quartiles (15.2%; 7.2 events/100 persons years; 95%CI 7.0 - 7.4; rate difference, 5.6 per 100 person years, 95%CI 5.2 - 5.9; HR, 0.21, 95%CI 0.05 - 90, multivariable adjusted HR, 0.20, 95%CI 0.05 - 0.88).Among breast cancer survivors, higher IL-8 at enrollment was associated with a decreased risk of incident and recurrent major depression. These findings provide insights into mechanisms of depression risk and development of novel therapies for depression prevention, and suggest that testing for IL-8 may have prognostic value in identifying resilience or risk of depression.

More and more studies have shown that ferroptosis is closely related to the progression of various diseases, but the significance of ferroptosis in psoriasis is still rarely explored. The detection of plasma and psoriatic lesions found that the contents of MDA and ROS were significantly increased, while the contents of SOD and GSH were significantly decreased, and the trend of increase or decrease in patients with progressive psoriasis was more obvious. The expression of ACSL4, a key regulator of ferroptosis, was significantly increased in psoriatic lesions and further up-regulated in patients with progressive psoriasis. ACSL4 expression was positively correlated with PASI score and the expression levels of inflammatory cytokines (TNF-α, IL-6, IL-8 and IL-17a), and linear regression analysis showed that high expression of ACSL4 in psoriatic lesions was associated with higher PASI score. Both ferroptosis inducer Erastin and IFN-γ/TNF-α significantly induced ferroptosis, inhibited keratinocyte viability, promoted the accumulation of MDA, ROS and Fe

Cationic antimicrobial protein of 37 kDa (CAP37), a neutrophil-derived protein originally identified for its antimicrobial activity, is now known to have many regulatory effects on host cells. However, its role in the pathogenesis of chronic obstructive pulmonary disease (COPD) has not been studied. We therefore investigated the expression of CAP37 in COPD and its effects on airway structural cells, including bronchial epithelial cells, smooth muscle cells, and fibroblasts.CAP37 was detected in the lung tissue, sputum, and plasma of COPD patients and the control subjects, as well as in the neutrophils stimulated by cigarette smoke extract (CSE). BEAS-2B cells, human bronchial smooth muscle cells (HBSMCs), and MRC-5 cells were treated with CAP37 or an anti-CAP37 antibody plus CAP37. Interleukin (IL)-6 and IL-8 were detected in the BEAS-2B cells. The cell proliferation was analyzed in the HBSMCs. Collagens were also detected in the MRC-5 cells.The expression of CAP37 was increased in the lung tissue and sputum supernatant of the COPD patients compared with the control subjects. The sputum supernatant CAP37 levels were inversely correlated with the forced expiratory volume in the first second percentage predicted in COPD. CAP37 was induced by CSE stimulation in the peripheral blood neutrophils from healthy non-smokers. CAP37 induced expression of IL-6 and IL-8 in BEAS-2B cells, and collagen expression of lung fibroblasts (MRC-5 cells). However, CAP37 did not significantly alter the proliferation of the HBSMCs.Our findings indicated that neutrophil-derived CAP37 may be involved in airway inflammation and fibrosis in COPD via affecting the bronchial epithelial cells, and fibroblasts, thus suggesting a possible role of CAP37 in the development and progression of COPD.

Abnormalities of the airway smooth muscle (ASM) layer in asthma may develop before birth. We hypothesize that antenatal inflammation causes physiological abnormalities of the ASM that predisposes asthma. This study determined the short-term effects of antenatal inflammation on the developing ASM. Fourteen pregnant ewes were randomly assigned to one of three groups. Fetal lambs were exposed to intra-amniotic injections of lipopolysaccharide (LPS

Biodiesel usage is increasing steadily worldwide as the push for renewable fuel sources increases. The increased oxygen content in biodiesel fuel is believed to cause decreased particulate matter (PM) and increased nitrous oxides within its exhaust. The addition of fuel additives to further increase the oxygen content may contribute to even further benefits in exhaust composition. The aim of this study was to assess the toxicity of 10% (v/v) diethylene glycol dimethyl ether (DGDME) added as a biodiesel fuel additive. Primary human airway epithelial cells were grown at the air-liquid interface and exposed to diluted exhaust from an engine running on either grapeseed, bran, or coconut biodiesel or the same three biodiesels with 10% (v/v) DGDME added to them; mineral diesel and air were used as controls. Exhaust properties, culture permeability, epithelial cell damage, and IL-6 and IL-8 release were measured postexposure. The fuel additive DGDME caused a decrease in PM and nitrous oxide concentrations. However, exhaust exposure with DGDME also caused decreased permeability, increased epithelial cell damage, and increased release of IL-6 and IL-8 (

To determine the metabolic activity, and cytokine expression over time from immortalized human corneal epithelial cells (HCECs) exposed to hyperosmotic stress.HCECs were cultured and expanded in DMEM/F-12 with 10% FBS. The cells were exposed to either normal media (295 mmol/kg) or hyperosmolar media (500 mmol/kg) for 0.25, 3, 6, and 12 hours. After each exposure duration, metabolic activity was quantified using alamarBlue, and a panel of pro-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, IFN-γ, and IL-17A) was quantified using multiplexed electrochemiluminescence (Meso Scale Diagnostics, Rockville, MD).Metabolic activity of the HCEC exposed to hyperosmolar conditions was significantly reduced at the 3-, 6-, and 12-hour mark compared to the control (allHyperosmolar stress reduced cell metabolic activity and increased expression of IL-1β, IL-4, IL6, IL8, IL-12p70, IL-13, and TNF-α over a 6-hour period in an immortalized HCEC line.

A critical and often-overlooked factor that may give rise to dandruff and oily hair is the intrinsic quality of the scalp stratum corneum (SC), which is often unbalanced and susceptible to external aggressions. Addressing the inflammation element of unhealthy scalp plays an important role in promoting healthy-looking and feeling hair. Although specialized pro-resolving lipid mediators (SPMs) have been studied in the skin to end the inflammation process and promote tissue regeneration, no studies have been provided in the scalp. This study aims to investigate SPMs expression and its role in improving scalp integrity and consequently improving hair appearance using an Anetholea anisita extract.The effect of Anetholea anisita extract was investigated in vitro on human follicle dermal papilla cells (HFDPC), evaluating its antioxidant and anti-inflammatory properties by fluorescence staining and ELISA, respectively. Ex vivo measurement of the volume of human scalp sebaceous glands was performed using X-ray microtomography (micro-CT). The extract was then clinically tested on a population of dandruff sufferers presenting oily hair. Volunteers' sebum was collected on the scalp and analysed by LC-MS/MS or ELISA to identify SPMs and pro-inflammatory markers. Scalp integrity was assessed by measuring the pH and the TEWL. Sebum production, dandruff and hair gloss were also evaluated.Anetholea anisita extract reduced IL-8 and reactive oxygen species (ROS) generation in HFDPC. Interestingly, this extract also decreased the volume of sebaceous glands as revealed by micro-CT. This result was confirmed in vivo by a decrease in sebum production in volunteers. Moreover, SPMs were analysed and detected in the scalp for the first time. An increase in Lipoxin B4 (LxB4) and Resolvin D1 and D2 (RvD1 and RvD2) was observed after Anetholea anisita treatment as well as decrease in pro-inflammatory sebum mediators expression such as PGE2, LTB4 and IL-8. Consequently, the scalp barrier was reinforced as observed through improved transepidermal water loss (TEWL) and skin surface pH, reducing dandruff and improving hair health.The present results suggest the potential of cosmetic applications of Anetholea anisita extract to improve scalp health by targeting inflammation pathways to decrease dandruff and improve hair condition.Un facteur important et peu étudié pouvant mener à l'apparition des pellicules ou des cheveux gras est la qualité intrinsèque du stratum corneum (SC) du cuir chevelu, souvent déséquilibré et susceptible aux agressions. L'inflammation joue un rôle clé dans l'état de santé du cuir chevelu et par conséquent du cheveu. Les médiateurs lipidiques pro-résolution (SPMs) ont été étudiés dans la peau pour mettre fin au processus inflammatoire et promouvoir la régénération des tissus. Cependant, aucune étude n'avait été réalisée sur le cuir chevelu. Cette étude vise donc à étudier l'expression des SPMs et leurs rôles dans l'amélioration de l'intégrité du cuir chevelu et de l'apparence des cheveux en utilisant un extrait de Anetholea anisita. MÉTHODES: Les propriétés antioxydantes et anti-inflammatoires de l'Anetholea anisita ont été étudiées in vitro sur les cellules papillaires folliculaires dermiques humaines (HFDPC) par fluorescence et ELISA. La mesure ex vivo du volume des glandes sébacées du cuir chevelu humain a été réalisée par microtomographie à rayons X (micro-CT). L'extrait a ensuite été cliniquement testé sur des volontaires présentant des pellicules et des cheveux gras. Le sébum des volontaires a été prélevé sur le cuir chevelu et analysé par LC-MS/MS ou ELISA pour identifier les SPMs et les marqueurs pro-inflammatoires. L'intégrité du cuir chevelu a ensuite été évaluée en mesurant le pH et la perte en eau transépidermique. La production de sébum, les pellicules et la brillance des cheveux ont également été évalués. RÉSULTATS: L'extrait d'Anetholea anisita a réduit la production d'IL-8 et d'espèces réactives oxygénées sur HFDPC. Cet extrait a également diminué le volume des glandes sébacées. Ce résultat a été confirmé in vivo avec une diminution de la production de sébum chez les volontaires. De plus, les SPMs ont été analysés et détectés pour la première fois sur le cuir chevelu. Une augmentation de la Lipoxine B4 (LxB4) ainsi que des Resolvines D1 et D2 (RvD1 et RvD2) a été observée après le traitement par Anetholea anisita en plus d'une diminution de l'expression des médiateurs pro-inflammatoires tels que PGE2, LTB4 et IL-8. Par conséquent, la barrière du cuir chevelu a été renforcée comme observé avec une diminution de la PIE et un ajustement pH de la surface du scalp, réduisant les pellicules et améliorant la santé des cheveux.Les résultats obtenus montrent qu'un extrait d'Anetholea anisita permet d'améliorer la santé du cuir chevelu en ciblant les voies de l'inflammation et de la résolution permettant ainsi de renforcer la barrière du cuir chevelu, pour diminuer les pellicules et améliorer l'état des cheveux.

Background: Several factors are thought to contribute to posttraumatic osteoarthritis (PTOA) development, including the posttraumatic inflammatory response. The purpose of this study was to compare 2 injuries at the same joint with a different severity and prognosis. This study compared the intra-articular inflammatory response after rotational ankle fracture (lower energy and less PTOA) with tibial plafond fracture (higher energy and more PTOA). Methods: This prospective comparative study was conducted at a level 1 trauma center between 2014-2019. Patients between 18 and 60 years of age with acute ankle or tibial plafond fractures were enrolled. Patients with preexisting ankle OA, autoimmune disease, additional injury, or open fractures were excluded. Synovial fluid aspirations were obtained within 24 hours of injury. The concentrations of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, IL-8, and IL-10 and matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 were quantified. Results: Aspiration were obtained from 29 plafond fractures and 36 ankle fractures. Mean age was 43 years, and patients were predominately female (64%). Age, gender, and comorbidities did not vary between cohorts. Of the plafond fractures, 13 were 43-B and 16 were 43-C injuries. Ankle fractures were predominately 44-B injuries, and 15 ankle fracture had articular impaction. IL-10, IL-1β, IL-6, IL-8, MMP-1, MMP-3, and MMP-13 were all significantly higher in acute plafond fractures as compared to acute ankle fractures. Conclusion: This study compared articular inflammatory marker profiles after fractures of different severities. Several cytokines were elevated in plafond fractures as compared to ankle fractures, suggesting a greater inflammatory response with plafond fractures. Given the difference in prognosis for and higher rate of PTOA after plafond fractures, these data strengthen the case that postinjury inflammatory response plays a role in PTOA development. Given that the postinjury inflammatory response is one of the few modifiable variables of these injuries, future research in this area remains important. Level of Evidence: Level II, prospective.

Biliary atresia (BA) is a severe cholestatic liver disease in children featuring cholestasis and liver fibrosis. The early diagnosis of BA is still challenging. This study aimed to evaluate the diagnostic values of matrix metalloprotease-7 (MMP-7), interleukin-8 (IL-8), and gamma-glutamyl transferase (GGT) in BA. Infants diagnosed with BA and non-BA between 2013 and 2018 were retrospectively analyzed. Plasma levels of MMP-7, IL-8, and GGT were measured in these infants. The receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were used to assess the diagnostic values of MMP-7, IL-8, and GGT. The expression of MMP-7 and IL-8 in the livers was detected by immunofluorescence staining. A total of 229 infants were enrolled in this study: 156 BA infants and 73 non-BA infants including 16 ones with infantile hepatitis syndrome. The plasma levels of MMP-7, IL-8, and GGT in BA infants had a median of 11.8 ng/mL (interquartile range, IQR: 5.3-57.5), 1.5 ng/mL (IQR: 1.0-2.8), and 381.0 U/L (IQR: 197.0-749.0), respectively, which were higher than non-BA subjects [MMP-7, 4.4 ng/mL (IQR: 3.3-6.1); IL-8, 0.7 ng/mL (IQR: 0.5-1.0); GGT, 59.0 U/L (IQR: 26.0-124.0)]. The AUC values of MMP-7, IL-8, and GGT for the diagnosis of BA were 0.8035, 0.8083, and 0.9126, respectively. The AUC values of MMP-7 + IL-8, MMP-7 + GGT, IL-8 + GGT, and MMP-7 + IL-8 + GGT for the diagnosis of BA were 0.8248, 0.9382, 0.9168, and 0.9392, respectively. The AUC values of MMP-7, IL-8, and GGT for differentiating BA infants with cholic stool from non-BA infants with cholic stool were 0.8006, 0.8258, and 0.9141, respectively. The expression of MMP-7 and IL-8 was increased in the cholangiocytes in BA livers. Conclusion: Plasma MMP-7, IL-8, and GGT alone or a combination of them has good accuracy to differentiate BA from non-BA and may be reliable biomarkers for BA. What is Known: • Biliary atresia (BA) is a severe cholestatic liver disease in children featuring cholestasis and progressive liver fibrosis. • Although early diagnosis of BA is crucial for good outcomes, it remains a clinical challenge. What is New: • Plasma MMP-7, IL-8, and GGT alone or a combination of them has good accuracy to differentiate BA from non-BA. • Plasma MMP-7, IL-8, and GGT have good accuracy for differentiating BA infants with cholic stool from non-BA infants with cholic stool.

Billions of individuals worldwide suffer from periodontal disease, an inflammatory disease that results in hard-tissue and soft-tissue destruction. A viable therapeutic option to treat periodontal disease may be via cannabinoids that exert immunomodulatory effects, and the endocannabinoid system (ECS) is readily present in periodontal tissues that exhibit cannabinoid type 1 and 2 receptors (CB1R and CB2R). Phytocannabinoids (pCBs), which are a part of a heterogeneous group of molecules acting on cannabinoid receptors (CBR) derived from the cannabis plants, have been attributed to a wide variety of effects including anti-inflammatory activity and some pro-inflammatory effects depending on the cell type. Thus, this study aims to examine the effects of pCBs on primary human gingival fibroblasts (HGFs) in IL-1β stimulated (simulated periodontal disease) HGFs.Human gingival fibroblasts (HGFs) obtained from ATCC were cultured per the manufacturer's recommendation. The functional activity of cannabinoid receptors was measured using ACTOne (cAMP)-based CB1R and CB2R assay. The effects of three pCBs (0.1-10 μg/ml or 10Cannabidivarin (CBVN or CBDV) (ECThe effective inhibition of IL-1β-stimulated production of PGE2 and cytokines by the pCB in HGFs suggests that targeting the endocannabinoid system may lead to the development of therapeutic strategies for periodontal therapy. However, each pCB has its unique anti-inflammatory profile, in which certain pro-inflammatory activities are also exhibited. The pCBs alone or in combination may benefit and aid in improving public oral health.

In brief Bovine granulosa cells need to be cultured with serum to generate inflammation in response to bacterial lipopolysaccharide. This study shows that it is cholesterol that facilitates this lipopolysaccharide-stimulated cytokine secretion. Abstract During bacterial infections of the bovine uterus or mammary gland, ovarian granulosa cells mount inflammatory responses to lipopolysaccharide (LPS). In vitro, LPS stimulates granulosa cell secretion of the cytokines IL-1α and IL-1β and the chemokine IL-8. These LPS-stimulated inflammatory responses depend on culturing granulosa cells with serum, but the mechanism is unclear. Here, we tested the hypothesis that cholesterol supports inflammatory responses to LPS in bovine granulosa cells. We used granulosa cells isolated from 4 to 8 mm and >8.5 mm diameter ovarian follicles and manipulated the availability of cholesterol. We found that serum or follicular fluid containing cholesterol increased LPS-stimulated secretion of IL-1α and IL-1β from granulosa cells. Conversely, depleting cholesterol using methyl-β-cyclodextrin diminished LPS-stimulated secretion of IL-1α, IL-1β and IL-8 from granulosa cells cultured in serum. Follicular fluid contained more high-density lipoprotein cholesterol than low-density lipoprotein cholesterol, and granulosa cells expressed the receptor for high-density lipoprotein, scavenger receptor class B member 1 (SCARB1). Furthermore, culturing granulosa cells with high-density lipoprotein cholesterol, but not low-density lipoprotein or very low-density lipoprotein cholesterol, increased LPS-stimulated inflammation in granulosa cells. Cholesterol biosynthesis also played a role in granulosa cell inflammation because RNAi of mevalonate pathway enzymes inhibited LPS-stimulated inflammation. Finally, treatment with follicle-stimulating hormone, but not luteinising hormone, increased LPS-stimulated granulosa cell inflammation, and follicle-stimulating hormone increased SCARB1 protein. However, changes in inflammation were not associated with changes in oestradiol or progesterone secretion. Taken together, these findings imply that cholesterol supports inflammatory responses to LPS in granulosa cells.

Hepatic encephalopathy (HE) is a neuropsychiatric disorder that results from either acute or chronic liver failure. CXCR2 plays an essential role in the pathophysiology of liver and brain diseases. In the present study, the potential beneficial effects of SB332235, a selective inhibitor of CXCR2, against HE were evaluated.HE was induced in male rats by thioacetamide injection (200 mg/kg, i.p.) at three alternative days. SB332235 was injected in rats 1 h before TAA at a dose of 1 and 3 mg/kg i.p.SB332235 alleviated oxidative stress as shown by the decreased serum NO and reduced MDA, elevated GSH and SOD levels, and reduced TNF-α and NF-κB levels in both brain and liver tissues of rats. Additionally, SB332235 suppressed brain ASK-1, JNK, IL-8, and caspase-3 expression, and activated PI3K/AKT expression in brain tissues. Markers of brain dysfunction, such as ammonia, and markers of hepatic injury, such as LDH, albumin, bilirubin, γGT, AST, ALT, and ALP, were significantly ameliorated. Also, the protective effect of SB332235 was confirmed by histological examination of both brain and liver tissues.Both doses (1 and 3 mg/kg) of SB332235 revealed significant hepatic/neuroprotective effects due to their anti-inflammatory, antioxidant, and antiapoptotic activities via activation of the PI3K/AKT pathway. Between the two, the 1 mg/kg dose provided significantly improved outcomes.

Acute ammonia toxicity suppresses the immune function and enhances the inflammatory pathways in Nile tilapia. The aim of this study was to compare the effect of Bacillus strains probiotic mixture (BS) or Yucca shidigera liquid extract (YSE) alone or their combination in water treatment and in reliving toxicity of an acute ammonia exposure in Nile tilapia through the assessment of fish immune response, inflammatory pathway, oxidative stress response with respect to the histopathological changes, gene expression, enzymes levels and phagocytosis. Five groups were used; the 1st and 2nd groups fed the basal diet; the 3rd group fed basal diet with BS in water, 4th group fed basal diet and supplemented with YSE in water and 5th group received a combination of BS and YSE. After two weeks of treatments, the 2nd, 3rd, 4th, and the 5th groups were exposed to acute ammonia challenge for 72 h. Fish exposed to ammonia displayed significant decreases in RBCs, Hb, PCV, WBCs, phagocytic activity (PA) and index (PI), lysozyme activities and serum antioxidant enzymes (glutathione peroxidase (GPX) and catalase (CAT)). Also, a significant increase in Malondialdehyde (MDA), degenerative changes in the gills, hepatopancrease and spleen associated with an elevated un-ionized ammonia level. A significant restoration of the hematological parameters was observed with the use of BS, YSE or their combination. Additionally, they improved the innate immunity, antioxidant responses, and histopathological changes. At transcriptomic level, ammonia toxicity significantly lowered the mRNA transcription levels of Nuclear erythroid 2-related factor 2 (Nrf2), quinone oxidoreductase 1 (NQO-1), Heme oxygenase 1 (HO-1) and Heat shock proteins (HSP70). While nuclear factor kappa β (NFкβ), Tumor necrosis factor α (TNF-α), Interleukin 1β (IL-1β), and Interleukin 8 (IL8), transcription levels were increased. Interestingly, BS and YSE and their combination significantly increased the expression of these genes with the highest levels reported with BS and YSE combination. We observed that, the most pronounced restoration of some important inflammatory and immune related genes close to the control level was observed when BS-YSE mix was used. Furthermore, a restored water pH, and a maintained ammonia level to the control level were observed in this group. Otherwise, equal effects for the three treatments were observed on the assessed parameters. We recommend the used of BS-YSE mix for water ammonia treatment and relieving ammonia toxicity in fish.

Advances in genomics and the gradual reduction of cost for technologies like whole-genome sequencing have provided exciting opportunities for developing modern biotechnological-based vaccines in aquaculture. This systemic review describes the prospects and challenges of implementing these high-tech vaccines in fish species. The majority of the commercial vaccines in aquaculture utilize conventional procedures for which cost of administration, protective immunity and safety issues are the major challenges. In recent years, more efficient vaccines are being developed by adopting the advances in vaccine technology. Vaccines based on surface antigens, protein/peptide/polysaccharide subunits, recombinant DNA/mRNA/plasmids, novel antigen expression and delivery systems (bacteriophage particles, virus like particles/VLPs, recombinant yeast, mucosal vaccines), novel molecular adjuvants (IL-8, IL-12, HSPs), and encapsulation polymers and polysaccharides like chitosan nanoparticles and PLGA microcapsule were successfully developed. These biotechnology-based vaccines have proved to be very efficient in field trials, but are always in the research pipeline or as patents. Only very few of them are licensed for use, that too, in high-valued fishes like salmonids. Currently, commercial aquaculture vaccines are available for Aeromonas salmonicida, Vibrio salmonicida, Yersinia ruckeri, Vibrio anguillarum, Edwardsiella ictalurid, and for certain Betanodaviruses. Nevertheless, no registered vaccines are available for other major infectious diseases/pathogens such as viral hemorrhagic septicemia virus (VHSV), viral nervous necrosis virus (VNN) and certain other betanodaviruses, channel catfish virus (CCV), gill disease bacteria, mycobacteria, flavobacterium, Edwardsiella tarda, and certain streptococci. Despite the important economic losses that the pathogens cause to aquaculture worldwide, the commercialization of vaccines remains limited due to immunological pitfalls in aquatic species, large-scale vaccination issues, unregulated use of antibiotics and chemicals, gene-based vaccine regulations and commercial viability. If attempts are to be made to develop novel delivery methods, cost-effective procedures, and relaxations in DNA vaccine regulations, biotechnology-based vaccination could circumvent the emerging disease challenges in aquaculture.

A 56-day feeding trial was conducted to examine the preventive and reparative functions of host-associated probiotics against high soybean meal (SM)-induced negative effects in Japanese seabass (Lateolabrax japonicus). Fish continuously fed low SM (containing 16% SM) and high SM (containing 40% SM) diets were named as positive (PC) and negative (C) control, respectively. Preventive functions of probiotics were evaluated by continuously feeding diets LF3 (Lactococcus petauri LF3 supplemented in high SM diet, group PLF3) and LF4 (Bacillus siamensis LF4 supplemented in high SM diet, group PLF4), while reparative functions were estimated by feeding the high SM diet during 0-28 days, then feeding diets LF3 (group RLF3) and LF4 (group RLF4) until day 56. Compared with the group PC, suppressed growth and immunity, and damaged intestinal health were observed in the group C on days 28 and 56. Fish in groups PLF3 and PLF4, rather than in groups RLF3 and RLF4, showed higher growth compared with the group C and displayed similar immune status to the group PC, indicating that the initial and continued application of probiotic LF3 and LF4 can efficiently improve high SM induced growth and immune deficiency in Japanese seabass, but probiotics had limited reparative benefits when they were administrated at the middle of the feeding trial (28 d). Furthermore, probiotics showed good preventive functions and limited reparative functions on gut health via improving intestinal morphology and inflammation markers, for example, decreasing diamine oxidase activity and d-lactate content, while up-regulating anti-inflammatory TGF-β1 expression and down-regulating pro-inflammatory TNF-α, IL-1β, and IL-8 expressions. Moreover, dietary supplementation of probiotics (especially on day 56) could effectively shape the gut microbiota, such as significantly decreasing abundances of opportunistic pathogens (phylum Actinobacteria, genera Pseudomonas and Moheibacter on day 28, phylum Proteobacteria, genus Plesiomonas on day 56), significantly increasing gut microbial diversity and abundances of possible beneficial bacteria (phylum Bacteroidetes and genus Lactobacillus on day 28, phyla Firmicutes, Bacteroidetes and Cyanobacteria, genera Bacillus, Lactobacillus and Bacteroides on day 56). In conclusion, we evidenced for the first time that host-associated L. petauri LF3 and B. siamensis LF4 can provide effectively preventive and certain reparative functions against high SM-induced adverse effects in L. japonicus.

The omega-3 polyunsaturated fatty acids (PUFAs) have an anti-inflammatory effect, beneficial for allergies, asthma, chronic obstructive pulmonary disease (COPD), reduce cholesterol and triglyceride levels and blood inflammatory parameters [C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α)]. The aim of our cross-sectional study was to monitor omega-3 supplementation in patients with severe COPD and assess its association with quality of life, nutritional status, inflammatory parameters, lipid profile, comorbidities, exercise tolerance and inhaled medications.Our questionnaire on dietary supplement habits and our validated self-completion questionnaires were filled in by 400 patients with COPD at the National Koranyi Institute of Pulmonology, Hungary, mean age 67 [61-73] years; forced expiratory volume in one second (FEV1) (ref%): 46 [34-58]; 47.5% male, 52.5% female. We used the disease-specific COPD Assessment Test (CAT) questionnaire to measure quality of life.More than half of the study participants (61%) did not consume fish or oilseeds at all. Nineteen patients (4.75%) took omega-3 supplementation regularly, mainly on medical advice (0.5 g/day). We observed significantly lower serum CRP levels [6.0 (1-7.3) vs. 9.7 (7.4-14.4); P=0.044], more favourable lipid profile [triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol] with higher mean body mass index (BMI) [28.1 (22.0-35.3) vs. 24.7 (24.5-30.1); P=0.118], better quality of life {CAT: 25 [21-30.5] vs. 26 [20-31]; P=0.519}, lower inhaled short-acting bronchodilators use [short-acting beta-agonists (SABAs): 6 (31.58) vs. 209 (54.86); P=0.047], lower number of exacerbations in the previous half year [0 (0-1) vs. 1 (0-2); P=0.023], and higher 6-minute walking distance (6MWD) {300 [177-387] vs. 251 [150-345]; P=0.120} in the group with omega-3 supplementation.PUFAs are anti-inflammatory and affect the immune system. Our study shows that omega-3 intake of COPD patients is insufficient, and there is an urgent need to develop new anti-inflammatory strategies because only one drug (such as corticosteroids) cannot ease the chronically progressive inflammatory process of COPD.

Fish are extremely vulnerable to environmental stimulation and produce oxidative stress. Among them, hydrogen peroxide is an oxidative stress source that cannot be ignored in fish, which can cause physical disorders, inflammation and even death. Taurine was revealed to reduce oxidative damage and inflammation caused by toxic substances, but whether it can reduce toxicity of rice field eel caused by H

Interferon (IFN)-induced protein 35 (IFI35, also known as IFP35), a member of IFN induced genes (ISGs), participates in virus infection, cancer progression and the chronic inflammatory diseases. However, its roles during fish nodavirus infection still remained largely unknown. In the present study, a homolog of IFI35 from orange spotted grouper (Epinephelus coioides) (EcIFI35) was cloned and characterized. The open reading frame of EcIFI35 was composed of 1,128 bp, and encoded a 375 amino acid polypeptide, which contained two conserved N-myc-interactor (Nmi)/IFP35 domains (NIDs). Homology analysis indicated that EcIFI35 shared 95.73% and 31.96% identity with homologs of giant grouper (E. lanceolatus) and human (Homo sapiens), respectively. The transcription of EcIFI35 was significantly up-regulated in grouper spleen (GS) cells after challenged with red-spotted grouper nervous necrosis virus (RGNNV), polyinosinic:polycytidylic acid [poly(I:C)] or lipopolysaccharide (LPS). The subcellular localization analysis showed that EcIFI35 encoded a cytoplasmic protein. The ectopic expression of EcIFI35 inhibited RGNNV replication by reducing viral genes transcription and protein synthesis. Co-immunoprecipitation (Co-IP) assay demonstrated that EcIFI35 interacted with RGNNV coat protein (CP), and partly co-localized with CP. EcIFI35 overexpression promoted the expression of IFN-related molecules and pro-inflammatory factors, including IFN regulatory factor 7 (IRF7), mitochondrial antiviral signaling protein (MAVS) and myxovirus resistance gene I (MxI), nuclear factor κB (NF-κB), interleukin 6 (IL-6) and IL-8. Together, our results revealed that EcIFI35 interacted with CP and inhibited fish nodavirus replication through positively regulated host innate immune response.

Amyloodiniosis is a severe disease of marine and brackish water fish caused by Amyloodinium ocellatum. Golden pompano (Trachinotus ovatus) is often repeatedly infected by A. ocellatum, leading to extensive mortality. However, little is known about the immune response mechanisms of the T. ovatus following reinfection with A. ocellatum. In this study, an extensive analysis at the transcriptome level of T. ovatus skin was carried out at 24 h post-infection by A. ocellatum. During the transcriptomic analysis, 1367 differentially expressed genes (DEGs) in the skin of T. ovatus under A. ocellatum infection and control conditions were obtained. In Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotated analyses, the DEGs were significantly enriched in the immune-related pathways. To better understand the immune-related gene expression dynamics, a quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to assess the primary and secondary infection groups of T. ovatus at different stages (3 h, 12 h, 24 h, 48 h and, 72 h post-infection) of infection with A.ocellatum. The results showed that innate immunity-related genes [interleukin (IL-8), chemokine ligand 3 (CCL3), toll-like receptor 7 (TLR7), and G-type lysosome (LZM g)] and adaptive immunity-related gene [major histocompatibility complex (MHC) alpha antigen I and MHC alpha antigen II] expression levels in the primary and secondary infection groups were significantly increased compared to the control group. The expression of MHC I and MHC II was more rapidly upregulated in the secondary infection group compared with the primary infection group after A.ocellatum infection. However, no significant differences of A.ocellatum load were observed in primary and secondary infection groups. In addition, the serum of the primary infection group had significantly higher concentrations of triglyceride (TG), higher alanine transaminase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) activities than the control group. This study contributes to understanding the defense mechanisms in fish skin against ectoparasite infection.

This study investigated the effects of dietary supplementation with anthocyanin extracted from black rice bran (AR) on the growth rate, immunological response, and expression of immune and antioxidant genes in Nile tilapia raised in an indoor biofloc system. A total of 300 Nile tilapia fingerlings (15.14 ± 0.032 g) were maintained in 150 L tanks and acclimatized for two weeks. Five experimental AR diets (0, 1, 2, 4, and 8 g kg

Individual and combined efficacy of chitooligosaccharides (COS) and alginic acid (AA) at 1 g, 2 g, and 3 g per kg diet was assessed on growth and disease resistance in silver carp (Hypophthalmichthys molitrix) against Edwardsiella ictaluri. Growth parameters including specific growth rate (SGR), weight gain (WG), and feed conversion rate (FCR) were significant in fish fed 2 g and 3 g kg

The experiment aimed to investigate the alteration of tea polyphenols (TP) in growth and immunity for hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂) fed high-lipid diets. Six concentrations of TP (0, 0.01, 0.02, 0.04, 0.08, 0.16%, named TP1 (basic diet control), TP2, TP3, TP4, TP5, TP6) were supplied in isonitrogenous (51%) and isolipidic (16.7%) experimental diets. These diets were fed to the juvenile grouper (8.68 ± 0.22 g) for 8 weeks. The results showed that dietary TP significantly increased the weight gain rate and specific growth rate (P 0.05), compared with the control group. The protein efficiency ratio in TP4 group was significantly higher than that of the control group (P 0.05). TP supplement in high-lipid diets increased antioxidant capacity in the serum (CAT, GSH-Px, T-AOC) and liver (SOD, CAT, GSH-Px, T-AOC). Additionally, dietary TP decreased oxidative stress (ROS, MDA) and improved immunity (ACP, AKP, LYS, IgM) in the liver. The histology of hepatic tissue indicated that dietary TP alleviated pathological symptoms caused by high-lipid diets. Compared with the control group, appropriate dietary TP significantly up-regulated expression of sod, cat, gsh-px, nrf2, keap1, hsp70, hsp90, myd88, tnfα and down-regulated expression of tlr22, il8, il1β, il10 in the liver (P 0.05). In the head kidney, expression of myd88, il1β, tnfα and il6 were significantly up-regulated and expression of tlr22 and il10 were significantly down-regulated by dietary TP (P 0.05). After the challenge of Vibrio harveyi, survival rate in higher doses of TP group (TP4 ∼ TP6) was evidently higher, compared with the control group. In conclusion, TP supplement in high-lipid diets improved antioxidant capacity and enhanced immunity of grouper. We speculate that TP may play the role of an immunostimulant, enhancing immunity and disease resistance by cytokine-medicated immune responses. Based on the second-order regression, 0.092-0.106% tea polyphenols were recommended in juvenile grouper high-lipid diets.

The association between herpetic/bacterial co-infection and periodontal diseases has been reported. However, how interactions between herpesviruses and periodontal bacteria dampen periodontal inflammation is still unclear. This study determined effects of co-infection with oral bacteria, including Streptococcus sanguinis, Fusobacterium nucleatum or Aggregatibacter actinomycetemcomitans, in herpes simplex virus type 1 (HSV-1)-infected oral epithelial cells.Cell viability was determined by detection the activity of mitochondrial dehydrogenase. Viral production was measured using the plaque assay. Levels of bacterial and viral DNA were determined by real-time polymerase chain reaction. Secretion of interleukin (IL)-6 and IL-8 was measured using the enzyme-linked immunosorbent assay.Viability was not further reduced by bacterial co-infection in HSV-1-infected cells. Co-infection with HSV-1 and S. sanguinis or F. nucleatum reduced the viral yield whereas co-infection with HSV-1 and A. actinomycetemcomitans significantly enhanced the viral yield in oral epithelial cells. The enhancing effect of A. actinomycetemcomitans was not affected by bacterial heat-inactivation. Co-infection with HSV-1/A. actinomycetemcomitans increased intracellular levels of both viral and bacterial DNA. Secretion of IL-6 and IL-8 stimulated by A. actinomycetemcomitans infection was partly reduced by co-infection with HSV-1 in oral epithelial cells.In contrast to S. sanguinis and F. nucleatum, A. actinomycetemcomitans enhanced the yield of HSV-1. Either HSV-1 or A. actinomycetemcomitans may be benefited from co-infection, in aspects of increases in production of viral and bacterial DNA as well as reductions in cytokine secretion. These findings echoed with previous clinical studies showing co-infection of HSV and A. actinomycetemcomitans in patients with aggressive periodontitis.

Inflammation plays an important role in the pathogenesis of stroke. The differential expression of inflammatory and angiogenic factors in thrombi and plasma remain undefined. In this observational cohort study, we evaluated angiogenic factors and inflammatory cytokines, in cerebral thrombi, local cerebral plasma (CP), and peripheral plasma (PP) in patients with acute ischemic stroke. Protein analysis of thrombi, CP and PP were used to measure angiogenic and inflammatory proteins using electrochemiluminescence. Our data indicate that VEGF-A, VEGF-C, bFGF, IL-4, IL-13, IL-1β, IL-2, IL-8, IL-16, IL-6 and IL-12p70 were higher in the thrombi of acute ischemic stroke patients than in the CP and PP of stroke patients. Moreover, the protein levels of GM-CSF were lower in the PP than in the CP and the clot. Moreover, VEGF-D, Flt-1, PIGF, TIE-2, IL-5, TNF-β, IL-15, IL-12/IL-23p40, IFN-γ and IL-17A were higher in PP and CP than in thrombi. Our results show that cytokines mediating the inflammatory response and proteins involved in angiogenesis are differentially expressed in thrombi within the cerebral and peripheral circulations. These data highlight the importance of identifying new biomarkers in different compartments of the circulatory system and in thrombi that may be used for the diagnosis and treatment of stroke patients.

Studies have reported that megakaryocytic leukemia 1 (MKL1) is closely related to the pathological process of a variety of inflammatory diseases, but its role in osteoarthritis (OA) needs to be clarified. This study aimed to investigate the regulatory role of MKL1 in oxidative stress-induced chondrocyte apoptosis and cartilage matrix degeneration. The expressions of target mRNAs and proteins were measured by using reverse transcription-quantitative polymerase chain reaction and western blotting. ELISA assay was used to measure the levels of IL-6, IL-8, and TNF-α in chondrocytes. And commercial kits based on different spectrophotometry or colorimetry methods were performed to validate oxidative stress. CCK-8 and apoptosis kits were used to determine cell viability and apoptosis. Rat OA model was established by anterior cruciate ligament transection (ACLT), and the expression of MKL1 was interfered by injecting sh-MKL1 lentiviral vector into caudal vein. The results showed that the expression of MKL1was induced by H

The immune-induced aplastic anemia (AA) mouse model has been used for the study of AA. However, there were no uniform conditions for establishing a model and no assessment of immunological homeostasis. Our study aimed to identify the conditions of establishing a model and assess the AA model in immunology and pathology.We induced an AA mouse model by the combination between sublethal irradiation and spleen-thymus lymphocyte infusion. The success of establishing the AA model was identified by blood routine tests and pathology of bone marrow. The frequency of Th17 and Treg cells was measured by flow cytometry. The frequency of CD34+ and CD41+ cells was detected by immunohistochemical technique.IL-6, IL-8, IL-17, TNF-α and IFN-γ were evaluated by ELISA.TheOur data suggest that the improved AA mouse model conforms to the diagnosis standard of AA and simulates the immune internal environment of human AA. The AA mouse model has a longer lifetime and unbalances of Th17/Treg cells caused the destruction of CD34+ cells and CD41+ cells, which was immune-mediated pathogenesis to adapt to long-term research.

We are currently screening human volunteers to determine their sputum polymorphonuclear neutrophil (PMN) response 6- and 24-hours following initiation of exposure to wood smoke particles (WSP). Inflammatory responders (≥10% increase in %PMN) are identified for their subsequent participation in mitigation studies against WSP-induced airways inflammation. In this report we compared responder status (lt;igt;Nlt;/igt; = 52) at both 6 and 24 hr time points to refine/expand its classification, assessed the impact of the GSTM1 genotype, asthma status and sex on responder status, and explored whether sputum soluble phase markers of inflammation correlate with PMN responsiveness to WSP.Six-hour responders tended to be 24-hour responders and vice versa, but 24-hour responders also had significantly increased IL-1beta, IL-6, IL-8 at 24 hours post WSP exposure. The GSTM1 null genotype significantly (lt;igt;plt;/igt; amp;lt; 0.05) enhanced the %PMN response by 24% in the 24-hour responders and not at all in the 6 hours responders. Asthma status enhanced the 24 hour %PMN response in the 6- and 24-hour responders. In the entire cohort (not stratified by responder status), we found a significant, but very small decrease in FVC and systolic blood pressure immediately following WSP exposure and sputum %PMNs were significantly increased and associated with sputum inflammatory markers (IL-1beta, IL-6, IL-8, and PMN/mg) at 24 but not 6 hours post exposure. Blood endpoints in the entire cohort showed a significant increase in %PMN and PMN/mg at 6 but not 24 hours. Sex had no effect on %PMN response.The 24-hour time point was more informative than the 6-hour time point in optimally and expansively defining airway inflammatory responsiveness to WSP exposure. GSTM1 and asthma status are significant effect modifiers of this response. These study design and subject parameters should be considered before enrolling volunteers for proof-of-concept WSP mitigation studies.

We hypothesized that yearling bulls selected for a 28-d breeding season would have reduced sperm concentrations and morphology, and have increased seminal plasma concentrations of pro-inflammatory cytokine interleukin-8 (IL-8). Yearling bulls were selected based on a breeding soundness examination (BSE) at approximately 415 d of age and contained at least 750 million sperm in the ejaculate, with 12 bulls randomly selected for breeding (BREEDERS) and 12 bulls not selected for breeding (NON-BREEDERS). After a 28-d breeding period, all bulls underwent a BSE. Plasma and seminal plasma were collected at each time point for analysis. Data were analysed utilizing either the MIXED or GLIMMIX procedures with repeated measures in SAS with breeding group, age and the interaction as fixed effects. Sperm concentration per ml of ejaculate was reduced (p .05) in yearling bulls used for breeding compared with those not used for breeding at the end of the breeding season. Seminal plasma IL-8 concentrations in yearling bulls used for breeding were increased (p .05) after the breeding season compared with bulls not used for breeding. Taken together, yearling bulls selected for a 28-d breeding season have reduced sperm production per ml of an ejaculate and increased inflammatory response in the seminal plasma that can lead to impaired breeding response if they are to be used for more than 30 d of breeding.

Clinical studies in healthy volunteers challenged with lipopolysaccharide (LPS), a constituent of the cell wall of Gram-negative bacteria, represent a key model to characterize the Toll-like receptor 4 (TLR4)-mediated inflammatory response. Here, we developed a mathematical modelling framework to quantitatively characterize the dynamics and inter-individual variability of multiple inflammatory biomarkers in healthy volunteer LPS challenge studies. Data from previously reported LPS challenge studies were used, which included individual-level time-course data for tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein (CRP). A one-compartment model with first-order elimination was used to capture the LPS kinetics. The relationships between LPS and inflammatory markers was characterized using indirect response (IDR) models. Delay differential equations were applied to quantify the delays in biomarker response profiles. For LPS kinetics, our estimates of clearance and volume of distribution were 35.7 L h(-1) and 6.35 L, respectively. Our model adequately captured the dynamics of multiple inflammatory biomarkers. The time delay for the secretion of TNF-alpha, IL-6 and IL-8 were estimated to be 0.924, 1.46 and 1.48 h, respectively. A second IDR model was used to describe the induced changes of CRP in relation to IL-6, with a delayed time of 4.2 h. The quantitative models developed in this study can be used to inform design of clinical LPS challenge studies and may help to translate preclinical LPS challenge studies to humans.

Feminizing hormonal therapy (FHT) and HIV potentially alter cardiovascular disease (CVD) risk in transgender women (TW).TW were enrolled in Los Angeles, California and Houston, Texas and frequency-matched to Multicenter AIDS Cohort Study cisgender men (CM) on age, race, substance use, and abacavir use. Biomarkers of CVD risk and inflammation were assessed via ELISA. Wilcoxon rank sum and Fisher's exact tests compared TW and CM. Multivariable linear regression assessed factors associated with biomarker concentrations.TW (HIV+ n = 75, HIV- n = 47) and CM (HIV+ n = 40, HIV- n = 40) had mean age 43-45 years; TW/CM were 90%/91% non-Hispanic Black, Hispanic, or Multiracial, 26%/53% obese, and 34%/24% current smokers; 67% of TW were on FHT. Among people with HIV (PWH), TW had higher median extracellular newly-identified receptor for advanced glycation end-products (EN-RAGE), lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), soluble tumor necrosis factor receptor type (sTNFR) I/II, interleukin (IL)-8 and plasminogen activator inhibitor (PAI)-1, but lower soluble CD14, von Willebrand factor (vWF) and endothelin (ET)-1 levels than CM. Findings were similar for participants without HIV (all P 0.05). In multivariable analysis, TW had higher EN-RAGE, IL-6, IL-8, P selectin, PAI-1, oxLDL and sTNFRI/II concentrations, and lower vWF, independent of HIV serostatus and current FHT use. Both being a TW and a PWH were associated with lower ET-1.Compared to matched cisgender men, trans women have altered profiles of biomarkers associated with systemic inflammation and CVD. Further work is needed to decipher the contributions of FHT to CVD risk in TW with HIV.

The disease caused by Micropterus salmoides rhabdovirus (MSRV) has brought substantial economic losses to the largemouth bass aquaculture industry in China. Vaccination was considered as a potential way to prevent and control this disease. As a kind of sustained and controlled release system, alginate and chitosan microspheres (SA-CS) are widely used in the development of oral vaccination for fish. Here, we prepared a king of alginate-chitosan composite microsphere to encapsulate the second segment of MSRV glycoprotein (G2 protein) and then evaluated the immune effect of the microsphere vaccine on largemouth bass. Largemouth bass were vaccinated via intragastric immunization by different treatments (PBS, SA-CS, G2 and SA-CS-G2). The results showed that a stronger immune response including serum antibody levels, immune-related physiological indexes (acid phosphatase, alkaline phosphatase, superoxide dismutase and total antioxidant capacity) and the expression of immune-related gene (IgM、IL-8、IL-1β、CD4、TGF-β、TNF-α) can be induced obviously with SA-CS-G2 groups compared with G2 groups when fish were vaccinated. Furthermore, fish were injected with a lethal dose of MSRV after immunization for 28 days, and the highest relative percentage survival (54.8%) was observed in SA-CS-G2 group (40 μg per fish), which is significantly higher than that of G2 group (25.8%). This study showed that alginate-chitosan microspheres as the vaccine carrier can effectively improve the immune effect of oral vaccination and induce better immune protection effect against MSRV infection.

The main risk factor for chronic obstructive pulmonary disease (COPD) is cigarette smoke (CS). It can alter many immune cells functions such as phagocytosis, efferocytosis and cytokine production. Cytokines play a role in the orchestration of inflammation in COPD. The JAK/STAT pathways are among the most important signalling components of cytokines. The objective of this work was to investigate the role of the JAK/STAT pathway with regard to cytokine release and microsphere uptake capacity (to minimize the non-specific scavenging) in human monocyte-derived-macrophages (MDMs). The MDMs were stimulated by cigarette smoke extract (CSE) alone or in combination with lipopolysaccharide (LPS). CSE alone was not associated with significant changes in the cytokine, with the exception of IL-8/CXCL8 production. However, CSE disturbed cytokine production in LPS-stimulated MDMs. CSE increase CXCL-8 and CCL2 release in LPS-stimulated monocyte-derived macrophages and suppressed the production of IL-6 and CXCL1 in these cells. CSE also decreased microsphere uptake capacity by MDMs. Then, CSE + LPS-stimulated MDMs were treated with two different JAK inhibitors. AG490 (specific inhibitor of JAK2) and ruxolitinib (inhibitor of JAK1 and JAK2). JAK/STAT inhibitors, particularly ruxolitinib, attenuated in cytokine production without completely inhibiting when compared with dexamethasone. On the other hand, the cells exposed to dexamethasone are nearly unable to capture the microspheres, while both JAK inhibitors do not affect the uptake capacity. In summary, our results showed the versatility of ruxolitinib which might bring a better balance disturbance of cytokine release and uptake capacity. The information regarding the distinctive effect of JAK/STAT inhibitors may be useful in the development of novel treatments for COPD.