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Selection for group living has occurred across taxa, despite inherent risk of disease transmission. Behavioral and immune responses to sickness affect social interactions and can be altered by social contexts. However, the majority of research on sickness behavior has focused on species that do not form selective social relationships. Prairie voles (Microtus ochrogaster) form selective social relationships with mates and peers and provide a useful study system to examine effects of sickness on social seeking in established relationships. We used peripheral injections of lipopolysaccharide (LPS) of E. coli to stimulate the innate immune system and verified effects on activity, core temperature, and corticosterone concentrations for 6 h following treatment. We demonstrated that male and female same-sex pairs of prairie voles increase social contact when sick and that this increase persists when contact is initiated by the sick vole. Finally, we assessed social motivation following immune challenge using operant choice chambers equipped with two levers and side chambers. Voles worked to gain access to chambers with social and non-social rewards. While overall effort decreased following LPS injection, only immune-challenged voles worked significantly harder for their companion than for a non-social chamber. LPS treatment also increased proportion of rewards earned for the partner versus a stranger and again led to increased huddling behavior. Prior studies in other rodent species have shown decreased social interaction when sick; the present results demonstrate an alternative outcome of sickness in the context of dyadic bonds and lay the foundation for future work in peer companions.

ABSTRACT Acute liver failure is a serious, life‐threatening disease. Although the gut microbiota has been considered to play a role in liver failure, the extent to which it is involved in the pathogenesis of this disease has not been fully elucidated to date. Therefore, we here analyzed the importance of the presence of intestinal microbiota in the pathogenesis of acute liver injury, using D‐galactosamine (D‐GalN)/lipopolysaccharide (LPS)‐treated mice, which is a widely used experimental model of acute liver injury. First, administration of the antibiotic polymyxin B markedly alleviated liver injury. Liver injury was also reduced in germ‐free mice, leading to the conclusion that the presence of intestinal microbiota aggravates D‐GalN/LPS‐induced liver injury. The amount of bacteria and LPS transferred from the gut to the blood was not increased by D‐GalN/LPS, suggesting that the worsening of liver injury was not simply owing to the entry of bacteria into the circulation. In conclusion, acute liver injury in polymyxin B‐pretreated or germ‐free mice was ameliorated by modulation of the gut microbiota. Modification of the gut microbiota using polymyxin B may hence have the potential to alleviate acute liver injury in human patients. [ABSTRACT FROM AUTHOR]

Lipopolysaccharides (LPS) are commonly used to construct inflammation models. However, poultry have a certain degree of tolerance to LPS due to the lack of thrombin XI and XII in their bodies. Thrombin activation produces clotting factors that can cleave prothrombin to form thrombin. The purpose of this study was to construct a chick oxidative stress model used different concentrations of LPS combined with thrombin in order to screen for the optimal concentration for constructing the oxidative stress model, and to explore the effects of this stimulus on various indicators of chicks. Eighty-one young chicks (4-days-old) were randomly divided into three groups with 27 chicks per group where each group contained 3 replicates with 9 birds each: a control group (physiological saline), a low-dose group (LPS 5 mg/kg thrombin 150 U/kg), and a high-dose group (LPS 10 mg/kg thrombin 300 U/kg). The results indicated that compared with the control group, the low-dose group and the high-dose group significantly increased the content of Malondialdehyde (MDA) in serum and reduced the content of T-AOC, GSH-PX and SOD, respectively. Meanwhile, the levels of NO and inflammatory factors IL-1β, IL-6 and TNF-α TNF-α in the liver were significantly increased in the low-dose and high-dose groups compared with the control group, respectively. Liver and thymus tissue sections from the low- and high-dose groups showed hemorrhage, hemolysis, and a small amount of exudation. In terms of inflammatory effect, the serum MDA content and the levels of NO, IL-1β, IL-6 and TNF-α factors in the liver were significantly increased in the low-dose group compared with the high-dose group. On histopathological observation, tissue damage was more pronounced in the low-dose group than in the high-dose group. In conclusion, LPS combined with thrombin could induce oxidative stress in chicks and the pathological changes of the low-dose effect are more pronounced. [ABSTRACT FROM AUTHOR]

Obesity is associated with a low-grade chronic inflammatory process characterized by higher circulating TNFα levels, thus contributing to insulin resistance. This study evaluated the effect of silybin, the main bioactive component of silymarin, which has anti-inflammatory properties, on TNFα levels and its impact on glucose uptake in the adipocyte cell line 3T3-L1 challenged with two different inflammatory stimuli, TNFα or lipopolysaccharide (LPS). Silybin's pre-treatment effect was evaluated in adipocytes pre-incubated with silybin (30 or 80 µM) before challenging with the inflammatory stimuli (TNFα or LPS). For the post-treatment effect, the adipocytes were first challenged with the inflammatory stimuli and then post-treated with silybin. After treatments, TNFα production, glucose uptake, and GLUT4 protein expression were determined. Both inflammatory stimuli increased TNFα secretion, diminished GLUT4 expression, and significantly decreased glucose uptake. Silybin 30 µM only reduced TNFα secretion after the LPS challenge. Silybin 80 µM as post-treatment or pre-treatment decreased TNFα levels, improving glucose uptake. However, glucose uptake enhancement induced by silybin did not depend on GLUT4 protein expression. These results show that silybin importantly reduced TNFα levels and upregulates glucose uptake, independently of GLUT4 protein expression. [ABSTRACT FROM AUTHOR]

Sickness sleep and rebound following sleep deprivation share humoral signals including the rise of cytokines, in particular interleukins. Nevertheless, they represent unique physiological states with unique brain firing patterns and involvement of specific circuitry. Here, we performed untargeted metabolomics of mouse cortex and hippocampus to uncover changes with sickness and rebound sleep as compared with normal daily sleep. We found that the three settings are biochemically unique with larger differences in the cortex than in the hippocampus. Both sickness and rebound sleep shared an increase in tryptophan. Surprisingly, these two sleep conditions showed opposite modulation of the methionine–homocysteine cycle and differences in terms of the energetic signature, with sickness impinging on glycolysis intermediates whilst rebound increased the triphosphorylated form of nucleotides. These findings indicate that rebound following sleep deprivation stimulates an energy rich setting in the brain that is devoid during sickness sleep. [ABSTRACT FROM AUTHOR]

1. This meta-analysis investigated the impact of LPS and covariates (serotype, rearing period and administration route) on the productivity parameters of broiler chickens (average daily feed intake (ADFI), average daily gain (ADG) and feed conversion ratio (FCR)). 2. Thirty-two eligible studies were included. Hedges' g effect size was determined using a random-effects model at 95% confidence interval. 3. Results showed that LPS significantly decreased average daily feed intake (ADFI; p < 0.0001) and average daily gain (ADG; p < 0.0001) and increased FCR (p < 0.0001). The serotypes Escherichia coli 055: B5 (EC055: B5) and Escherichia coli 0127: B8 (EC 0127: B8) significantly reduced ADFI and ADG, and the serotype EC 055: B5 significantly increased the FCR (p < 0.05). 4. The intraperitoneal administration of the LPS significantly reduced the productivity of broiler chickens (p < 0.05), but other administration routes did not show such effects. The reduction in ADFI and ADG was found in all rearing periods (p < 0.05), and the increase in FCR was observed in the starter (p = 0.0302) and grower periods (p = 0.0031). 5. Exposure to LPS significantly reduced the productivity of broiler chickens (p < 0.05). However, no relationship was observed between LPS dosage and productivity as indicated by the meta-regression study. 6. The findings indicated that LPS has detrimental effects on broiler chickens' ADFI, ADG and FCR across various LPS serotypes and rearing periods. These detrimental impacts of LPS remain consistent regardless of the administered dosage. [ABSTRACT FROM AUTHOR]

Handball is one of the most popular team sports and requires the correct analysis of players' physical condition for its development, especially in women´s handball. Therefore, the aim of this study was to analyse for the first time the competitive demands of professional handball players during the EHF Championship 2020, using the innovative Local Positioning System (LPS) technology. In order to achieve this goal, 231 female players from 16 national teams were analysed during 47 matches using LPS and a specific handball analytic system developed for this purpose. Players covered more distance in the offensive phase (1205.6 ± 636.7 m) and in all locomotion categories, with the exception of high intensity running, than in the defensive phase (834.2 ± 471.5 m), with a similar average total time on court. The running pace was significantly higher in attack (56.0 ± 26.2 m/min) than in defence (39.2 ± 19.8 m/min). Regarding playing positions, wing players covered higher distances in the high intensity categories than the rest of the playing positions. It could be concluded that the training workload of elite handball players should be programmed according to specific positions. [ABSTRACT FROM AUTHOR]

Inflammation is a complex physiological process that enables the clearance of pathogens and repairing damaged tissues. Elevated serum copper concentration has been reported in cases of inflammation, but the role of copper in inflammatory responses remains unclear. This study used bovine macrophages to establish lipopolysaccharide (LPS)-induced inflammation model. There were five groups in the study: a group treated with LPS (100 ng/ml), a group treated with either copper chelator (tetrathiomolybdate, TTM) (20 μmol) or CuSO4 (25 μmol or 50 μmol) after LPS stimulation, and a control group. Copper concentrations increased in macrophages after the LPS treatment. TTM decreased mRNA expression of pro-inflammatory factors (IL-1β, TNF-α, IL-6, iNOS, and COX-2), whereas copper supplement increased them. Compared to the control group, TLP4 and MyD88 protein levels were increased in the TTM and copper groups. However, TTM treatment decreased p-p65 and increased IкB-α while the copper supplement showed reversed results. In addition, the phagocytosis and migration of bovine macrophages decreased in the TTM treatment group while increased in the copper treatment groups. Results mentioned above indicated that copper could promote the LPS-induced inflammatory response in bovine macrophages, promote pro-inflammatory factors by activating the NF-кB pathway, and increase phagocytosis capacity and migration. Our study provides a possible targeted therapy for bovine inflammation. [ABSTRACT FROM AUTHOR]

Pneumonia is a serious and life‐threatening lung inflammation with high morbidity and mortality. Accumulating evidence has suggested that esculin, a derivative of coumarin, possesses potent anti‐inflammatory effects. This study is designed to explore the pharma role and underlying mechanism of esculin against lipopolysaccharides (LPS)‐induced pneumonia. TC‐1 cells were stimulated by LPS to mimic the inflammatory injury model in vitro. Cell viability, proliferation, and apoptosis were determined using MTT assay, 5‐ethynyl‐2′‐deoxyuridine assay, and flow cytometry. Interleukin‐1β and tumor necrosis factor α levels were analyzed using an enzyme‐linked immunosorbent assay. Reactive oxygen species and superoxide dismutase were examined using special assay kits. Macrophage polarization was detected using flow cytometry. Mitogen‐activated protein kinase 14 (MAPK14) level was detected by real‐time quantitative polymerase chain reaction. MAPK14 and ubiquitin‐specific protease 7 (USP7) protein levels were determined using western blot assay. After Ubibrowser database prediction, the interaction between USP7 and MAPK14 was verified using a Co‐immunoprecipitation assay. The biological role of esculin was verified in LPS‐challenged ALI mice in vivo. Here, we found that esculin significantly relieved LPS‐induced TC‐1 cell proliferation inhibition, and apoptosis, inflammatory response, oxidative stress, and M1‐type macrophage polarization promotion. MAPK14 and USP7 expressions were enhanced in LPS‐treated TC‐1 cells, which was partly abolished by esculin treatment. Overexpressing MAPK14 attenuated the repression of esculin on LPS‐triggered TC‐1 cell injury. At the molecular level, USP7 interacted with MAPK14 and maintained its stability by removing ubiquitin. Moreover, esculin repressed the progression of pneumonia in vivo by regulating MAPK14. Taken together, esculin exposure could mitigate LPS‐induced TC‐1 cell injury partly by targeting the USP7/MAPK14 axis, providing a better understanding of the role of esculin in the anti‐inflammatory therapeutics for pneumonia. Esculin treatment could relieve LPS‐induced TC‐1 cell proliferation inhibition, and apoptosis, inflammation, oxidative stress, macrophage M1 polarization promotion in vitro, as well as pneumonia progression in vivo by regulating the USP7/mitogen‐activated protein kinase 14 (MAPK14) axis. Furthermore, USP7 could facilitate protein stability and MAPK14 expression in TC‐1 cells. [ABSTRACT FROM AUTHOR]

Background: Intestinal barrier dysfunction and systemic inflammation are common in obstructive sleep apnoea (OSA). We aimed to investigate the role of melatonin, an anti-inflammatory mediator, in mediating the relationships between OSA, intestinal barrier dysfunction and systemic inflammation. Methods: Two hundred and thirty-five male participants who complained with sleep problems and underwent whole night polysomnography at our sleep centre between 2017 and 2018 were enrolled. Polysomnographic data, anthropometric measurements and biochemical indicators were collected. Serum melatonin, intestinal barrier function biomarker zonula occludens-1 (ZO-1) and inflammatory biomarkers C-reactive protein (CRP) with lipopolysaccharide (LPS) were detected. Spearman's correlation analysis assessed the correlations between sleep parameters, melatonin and biomarkers (ZO-1, LPS and CRP). Mediation analysis explored the effect of OSA on intestinal barrier dysfunction and systemic inflammation in moderate-severe OSA patients. Results: As OSA severity increased, serum melatonin decreased, whereas ZO-1, LPS and CRP increased. Spearman's correlation analysis showed that serum melatonin was significantly negatively correlated with ZO-1 (r = -0.19, p < .05) and LPS (r = -0.20, p < .05) in the moderate-OSA group; serum melatonin was significantly negatively correlated with ZO-1 (r = -0.46, p < .01), LPS (r = -0.35, p < .01) and CPR (r = -0.30, p < .05) in the severe-OSA group. Mediation analyses showed melatonin explain 36.12% and 35.38% of the effect of apnoea-hypopnea index (AHI) on ZO-1 and LPS in moderate to severe OSA patients. Conclusions: Our study revealed that melatonin may be involved in mediating intestinal barrier dysfunction and systemic inflammation in moderate-to-severe OSA patients. [ABSTRACT FROM AUTHOR]

Treatment for acute kidney injury (AKI) is suboptimal. A better understanding of the pathogenesis of AKI may lead to new therapeutic approaches. Kidney transcriptomics of folic acid‐induced AKI (FA‐AKI) in mice identified Runx1 as the most upregulated RUNX family gene. We then examined the expression of RUNX1 in FA‐AKI, in bacterial lipopolysaccharide (LPS)‐induced cytokine storm‐AKI (CS‐AKI), and in human AKI. In cultured mouse tubule cells, we explored the expression and role of RUNX1 in response to the cytokine TWEAK or LPS. A chemical inhibitor of RUNX1 (Ro5‐3335) was used in animal models of AKI to test its potential as a therapeutic target. RUNX1 overexpression in FA‐AKI was validated at the mRNA and protein levels and localized mainly to tubule cell nuclei. CS‐AKI also upregulated kidney RUNX1. Increased tubule and interstitial RUNX1 expression were also observed in human AKI. In cultured mouse tubule cells, the pro‐inflammatory cytokine TWEAK and LPS increased RUNX1 and IL‐6 expression. Mechanistically, RUNX1 bound to the Il6 gene promoter and RUNX1 targeting with the chemical inhibitor Ro5‐3335, or a specific small interfering RNA (siRNA), prevented the TWEAK‐ and LPS‐induced upregulation of IL6 through a RUNX1/NFκB1 p50 pathway. In vivo, preventive Ro5‐3335 improved kidney function and reduced inflammation in FA‐AKI and CS‐AKI. However, Ro5‐3335 administration after the insult only improved kidney function in CS‐AKI. Kidney transcriptomics identified inflammatory genes and transcription factor mRNAs such as Yap1 and Trp53 as key targets of Ro5‐3335 in CS‐AKI. In conclusion, RUNX1 contributes to AKI by driving the expression of genes involved in inflammation and represents a novel therapeutic target in AKI. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Helicobacterpylori colonizes the human gastric mucosa of more than half of the human population and has a unique lipopolysaccharide (LPS) structure. LPS is the most dominant and suitable pathogen-associated molecular pattern that is detected via pattern recognition receptors. Although the priming effect of H. pylori LPS on reactive oxygen species (ROS) production of PMNs is lower than that of Escherichia coli O111:B4 LPS, LPS released from H. pylori associated with antibiotics eradication therapy may activate PMNs and increase ROS production. In addition, we describe the effects of H. pylori and E. coli O111:B4 LPSs on gene expression and the anti-inflammatory effect of lansoprazole (LPZ) in human polymorphonuclear leukocytes. LPS isolated from H. pylori and E. coli O111:B4 alters toll-like receptor 2 (TLR) and TLR4 expressions similarly. However, LPS from E. coli O111:B4 and H. pylori caused a 1.8-fold and 1.5-fold increase, respectively, in CD14 expression. All LPS subtypes upregulated TNFα and IL6 expression in a concentration-dependent manner. Although E. coli O111:B4 LPS upregulated IL8R mRNA levels, H. pylori LPS did not (≦ 100 ng/mL). Gene expression levels of ITGAM demonstrated no significant change on using both LPSs. These different effects on the gene expression in PMNs may depend on variations in LPS structural modifications related to the acquired immunomodulatory properties of H. pylori LPS. Proton pump inhibitors, i.e., LPZ, are used in combination with antibiotics for the eradication therapy of H. pylori. LPZ and its acid-activated sulphenamide form AG-2000 suppress ROS production of PMNs in a dose-dependent manner. These results suggest that LPZ combination with antibiotics for H. pylori eradication reduces gastric inflammation by suppressing ROS release from PMNs. [ABSTRACT FROM AUTHOR]

This study aimed to analyse the influence of different physical fitness levels of youth basketball players on match-related physical performance, using Random Forest clustering to distinguish between high-fitness level players and low-fitness level players. Twenty male youth basketball players completed the following physical performance tests in two separate sessions: bilateral and unilateral countermovement jumps, bilateral and unilateral horizontal jumps, single leg lateral jumps, the 20 m linear straight sprint test, the 505 test and a repeated sprint ability test. 1 week after the second testing day, players completed a simulated match while external loads were monitored using an ultra-wide band-based Local Positioning System. A Random Forest clustering was used to create two different clusters composed of players with similar physical fitness attributes (high- and low-fitness level players). Results indicate that the Random Forest clustering adequately discriminated among the players in different groups according to their physical fitness attributes. High-fitness level players covered more distance per min in all intensity thresholds and reached higher maximal speed and acceleration intensity during the simulated matches (p < 0.05). These results may assist basketball practitioners in understanding running performance variations during matches and can be used to optimise preparation for individual players. [ABSTRACT FROM AUTHOR]

Autism spectrum disorders (ASD) have a complex pathogenesis thought to include both genetic and extrinsic factors. Among the latter, inflammation of the developing brain has recently gained growing attention. However, how genetic predisposition and inflammation might converge to precipitate autistic behavior remains elusive. Cerebellar structure and function are well known to be affected in autism. We therefore used cerebellar slice cultures to probe whether inflammatory stimulation and (over)expression of the autism susceptibility gene Engrailed-2 interact in shaping differentiation of Purkinje cells, key organizers of cerebellar histogenesis and function. We show that lipopolysaccharide treatment reduces Purkinje cell dendritogenesis and that this effect is enhanced by over-expression of Engrailed-2 in these cells. The effects of lipopolysaccharide can be blocked by inhibiting microglia proliferation and also by blocking tumor necrosis factor alpha receptor signaling, suggesting microglia and tumor necrosis factor alpha are major players in this scenario. These findings identify Purkinje cells as a potential integrator of genetic and environmental signals that lead to an autism-associated morphology. [ABSTRACT FROM AUTHOR]

Inflammation can be an unwanted consequence or cause of debilitating diseases of infectious and non-infectious aetiologies. Current anti-inflammatory medications have several deficiencies including lack of specificity and undesirable side effects. Herein, the potential of non-ionic surfactant vesicles (NISV) comprised of monopalmityol glycerol, dicetyl phosphate and cholesterol) as an anti-inflammatory drug and their mode of action is investigated. NISV were able to inhibit LPS-induced IL-6 from BMD macrophages. The individual components of NISV, monopalmityol glycerol, dicetyl phosphate and cholesterol did not affect LPS induced IL-6 levels, proving that formulation of NISV is essential for their anti-inflammatory effects. Transcriptomic analyses showed NISV mediated down-regulation of transcripts for inflammatory mediators in LPS stimulated macrophages. Notably, NISV downregulate NF-κB transcripts in LPS stimulated macrophages. Measurement of inflammatory mediators by cytometric bead array validated a number of transcriptomic findings as NISV were found to inhibit LPS induced IL-6, IL-12, and multiple chemokines. Further investigation demonstrated that NISV inhibited Poly(I:C) or Pam3csk4 induced inflammatory mediators. This indicates that the effects of NISV are distal to both MyD88 and TRIF signalling. Overall, the data generated highlights the potential of NISV as an anti-inflammatory therapeutic. [ABSTRACT FROM AUTHOR]

Introduction: Bacteremia is a life-threatening condition that can progress to sepsis and septic shock, leading to significant mortality in the emergency department (ED). The standard diagnostic method, blood culture, is time-consuming and prone to false positives and false negatives. Although not widely accepted, several clinical and artificial intelligence-based algorithms have been recently developed to predict bacteremia. However, these strategies require further identification of new variables to improve their diagnostic accuracy. This study proposes a novel strategy to predict positive blood cultures by assessing sepsis-induced immunosuppression status through endotoxin tolerance assessment. Methods: Optimal assay conditions have been explored and tested in sepsis-suspected patients meeting the Sepsis-3 criteria. Blood samples were collected at ED admission, and endotoxin (lipopolysaccharide, LPS) challenge was performed to evaluate the innate immune response through cytokine profiling. Results: Clinical variables, immune cell population biomarkers, and cytokine levels (tumor necrosis factor [TNFα], IL-1β, IL-6, IL-8, and IL-10) were measured. Patients with positive blood cultures exhibited significantly lower TNFα production after LPS challenge than did those with negative blood cultures. The study also included a validation cohort to confirm that the response was consistent. Discussion: The results of this study highlight the innate immune system immunosuppression state as a critical parameter for sepsis diagnosis. Notably, the present study identified a reduction in monocyte populations and specific cytokine profiles as potential predictive markers. This study showed that the LPS challenge can be used to effectively distinguish between patients with bloodstream infection leading to sepsis and those whose blood cultures are negative, providinga rapid and reliable diagnostic tool to predict positive blood cultures. The potential applicability of these findings could enhance clinical practice in terms of the accuracy and promptness of sepsis diagnosis in the ED, improving patient outcomes through timely and appropriate treatment. [ABSTRACT FROM AUTHOR]

Epidemiologically, one of the most important concerns associated with introducing Salmonella spp. into the environment and food chain is the presence of asymptomatic carriers. The oncogenic and oncolytic activity of Salmonella and their lipopolysaccharides (LPSs) is important and research on this topic is needed. Even a single asymptomatic dose of the S. Enteritidis LPS (a dose that has not caused any symptoms of illness) in in vivo studies induces the dysregulation of selected cells and bioactive substances of the nervous, immune, and endocrine systems. LPSs from different species, and even LPSs derived from different serotypes of one species, can define different biological activities. The activity of low doses of LPSs derived from three different Salmonella serotypes (S. Enteritidis, S. Typhimurium, and S. Minnesota) affects the neurochemistry of neurons differently in in vitro studies. Studies on lipopolysaccharides from different Salmonella serotypes do not consider the diversity of their activity. The presence of an LPS from S. Enteritidis in the body, even in amounts that do not induce any symptoms of illness, may lead to unknown long-term consequences associated with its action on the cells and biologically active substances of the human body. These conclusions should be important for both research strategies and the pharmaceutical industry &. [ABSTRACT FROM AUTHOR]

Background: Gut microbiome dysbiosis and related immune dysfunction have been associated with the pathogenesis of Human Cytomegalovirus (HCMV) infection in infants with neonatal cholestasis (NC) as previously reported by us. However, the interaction of a perturbed microbiome, HCMV infection, and dysregulated immunity leading to exacerbation of disease severity has not been investigated so far. In this study, we examined the association of gut microbiome, host inflammatory and homeostatic markers that are likely to govern increased pathogenesis of NC in HCMV infected IgM positive infants (N = 15) compared to IgM negative (N = 15) individuals. Stool samples of HCMV infected infants and age-matched healthy controls (N = 10) were assessed for gut bacteria-derived metabolites like short-chain fatty acids (SCFAs), Lipopolysaccharide (LPS), cytokines and markers of gut barrier integrity. Data were correlated with previously determined gut microbiome composition and frequency of immune cell subsets. Finally, validation of clinical potential was undertaken by principal component analysis (PCA) of integrated data to delineate the spectrum of clinical pathology. Results: Significantly lower levels of SCFAs and elevated fecal levels of soluble inflammatory mediators were observed in IgM positive HCMV infected infants. Further, increased plasma LPS levels and markers of gut permeability, suggestive of microbial translocation due to a 'leaky gut' were observed in HCMV infected IgM positive group. PCA of integrated data revealed clearly disparate profiles representative of IgM positive, IgM negative, and uninfected healthy states. Conclusion: Our results suggest the utility of an integrated approach involving dysregulated microbiome-immune axis for gaining a better understanding of pathogenesis associated with HCMV infection in NC. [ABSTRACT FROM AUTHOR]

Bacteriophage (phage) AP1 has been reported to effectively lyse Acidovorax oryzae, the causative agent of bacterial brown stripe in rice. However, phage AP1 exhibits strain-specific lysis patterns. In order to enhance the potential of phages for biological control of rice bacterial brown stripe, this study investigated the possible mechanism of strain-specific infection by characterizing phage AP1 and its susceptible (RS-2) and resistant (RS-1) strains. Based on the current classification standards and available database information, phage AP1 was classified into the class Caudoviricetes, and it is a kind of podophage. Comparative analysis of the susceptible and resistant strains showed no significant differences in growth kinetics, motility, biofilm formation, or effector Hcp production. Interestingly, the resistant strain demonstrated enhanced virulence compared to the susceptible strain. Prokaryotic expression studies indicated that six putative structural proteins of phage AP1 exhibited varying degrees of binding affinity (1.90–9.15%) to lipopolysaccharide (LPS). However, pull-down assays and bacterial two-hybrid analyses revealed that only gp66 can interact with four host proteins, which were identified as glycosyltransferase, RcnB, ClpB, and ImpB through immunoprecipitation and mass spectrometry analyses. The role of LPS in the specific infection mechanism of phage AP1 was further elucidated through the construction of knockout mutant strains and complementary strains targeting a unique gene cluster (wbzB, wbzC, wbzE, and wbzF) involved in LPS precursor biosynthesis. These findings provide novel insights into the mechanisms of phage-host specificity, which are crucial for the effective application of phage AP1 in controlling rice bacterial brown stripe. [ABSTRACT FROM AUTHOR]

Objective：To analyze the epidemiological characteristics of brucellosis patients, and to explore the diagnostic value of lipopolysaccharide (LPS) testing for brucellosis and the therapeutic effect of LPS combined with blood culture on brucellosis. Methods： A total of 61 clinical patients with brucellosis was collected and divided into the current brucellosis group (n=39) and the brucellosis treatment effective group (n=22), the current brucellosis group consisted of 32 cases in the initial diagnosis group and 7 cases in the treatment ineffective group, twenty healthy subjects were used as the normal control group. The clinical characteristics of the patients were retrospectively analyzed, and LPS content was examined quantitatively. The results of blood culture, rose Bengal plate agglutination test (RBT) and LPS level were analyzed. The positive rates of the three detection methods were compared, and the diagnostic sensitivity, specificity, accuracy, negative/positive predictive values, and the diagnostic efficacy of combined diagnosis were evaluated. Results：Among 39 present patients, and the positive rate of LPS test was 100%, higher than those of blood culture (82.05%) and RBT test (97.44%) . In 22 patients with effective treatment, the blood culture results were all negative. The false positive rates of LPS and RBT tests were 45.45% and 90.91%, respectively. The LPS level in the treatment effective group were significantly lower than those in the initial diagnosis group and the treatment ineffective group, and there was no statistically significant difference compared to the normal control group. The area under curve (AUC) values of blood culture combined with RBT, blood culture combined with LPS, RBT combined with LPS, and the combination of all three were 0.914, 0.957, 0.779, and 0.959, respectively. Since the AUC value for the combination of all three did not show a significant increase compared to the combination of blood culture with LPS, we choose the combination of blood culture with LPS as the indicator for evaluating the efficacy of brucellosis treatment. Conclusion：LPS detection has a high value in the diagnosis of present brucellosis and the evaluation of therapeutic effect of brucellosis. It can be used for the diagnosis of brucellosis in key population, improve the diagnosis rate and predict the outcome of the disease. [ABSTRACT FROM AUTHOR]

Immune defense is fundamental to diminish the negative effects of the attack of infectious agents, yet the activation of the immune system entails costs and may compromise other life-history traits such as reproduction. In reproductive brown booby pairs (Sula leucogaster), we experimentally imposed an immune challenge during incubation, by intraperitoneally injecting Escherichia coli lipopolysaccharide (LPS), in either the male or the female. We aimed to test whether activation of the immune response results in (1) an increase in oxidative stress parameters, (2) a decline in post-hatching parental care in the treated individual, and (3) a compensation of the post-hatching parental effort by the nontreated mate. We found that activation of the immune response during incubation did not increase oxidative damage to lipids or total antioxidant capacity. However, mounting an immune response compromised parental effort during the chick-rearing period: compared to controls, LPS-treated parents showed roughly a 50% decline in the rate of preening and offspring feeding in response to begging. Interestingly, mates of LPS-treated parents increased their feeding rate suggesting parental care compensation. According to a scenario of full compensation, the decline in parental effort of LPS-treated parents did not result in poorer offspring growth or immune response, or increased levels of oxidative stress parameters. These findings suggest that in a long-lived species with long-lasting biparental care, an immune challenge compromises parental care, favoring parental compensation as a strategy to mitigate costs in terms of offspring success. [ABSTRACT FROM AUTHOR]

The pars tuberalis (PT) plays an important role in the photoperiodic regulation of the secretory activity of the pituitary gland. Additionally, PT secretory activity may be influenced by the animal's immune status. The melatonin signal processing in PT cells occurs through the presence of melatonin receptors and the expression of molecular clock genes. This study aimed to define the effects of acute inflammation induced by intravenous administration of lipopolysaccharide (LPS) on the expression of clock genes in the PT of ewes under different photoperiodic conditions. Two analogous experiments were conducted in different photoperiods: short-day and long-day. Both experiments included 24 sheep divided into two groups: day (n = 12) and night (n = 12), further subdivided into a control group (n = 6) and a group treated with LPS (n = 6) at a dose of 400 ng/kg. Under short-day conditions, the expression of clock circadian regulator, basic helix-loop-helix ARNT like 1, cryptochrome circadian regulator (CRY) 1, 2, and casein kinase 1 epsilon genes was lower during inflammation. LPS injection increased expression of the period circadian regulator 1 gene during the night. Under long-day conditions, CRY1 mRNA level was lower during the night, while diurnal CRY2 mRNA expression was decreased after LPS injection. Our results showed that inflammation disturbed the expression of molecular clock genes in the PT; however, this influence was partly dependent on photoperiod conditions. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, characterized by the accumulation of amyloid-beta (Aβ) plaques and neuroinflammation. This study investigates the protective effects of noradrenaline (NA) on human microglial cells exposed to lipopolysaccharides (LPS) and Aβ aggregates—major contributors to inflammation and cellular damage in AD. The reduced Aβ aggregation in the HMC3 human microglial cells co-treated with Aβ and NA was confirmed by thioflavin T (ThT) assay, fluorescent ThT staining, and immunocytochemistry (ICC). The significantly increased viability of HMC3 cells after 48 h of incubation with NA at 50 µM, 25 µM, and 10 µM, exposed to IC50 LPS and IC50 Aβ, was confirmed by XTT and LDH assays. Moreover, we found that NA treatment at 25 μM and 50 μM concentrations in HMC3 cells exposed to IC50 LPS or IC50 Aβ results in an increased proliferation of HMC3 cells, their return to normal morphology, decreased levels of DNA damage, reduced caspase-3 activity, decreased expression of pro-apoptotic DDIT3 and BAX, and increased expression of anti-apoptotic BCL-2 genes and proteins, leading to enhanced cell survival, when compared to that of the HMC3 cells treated only with IC50 LPS or IC50 Aβ. Furthermore, we showed that NA induces the degradation of both extracellular and intracellular Aβ deposits and downregulates hypoxia-inducible factor 1α (HIF-1α), which is linked to impaired Aβ clearance and AD progression. These findings indicate that NA holds promise as a therapeutic target to address microglial dysfunction and potentially slow the progression of AD. Its neuroprotective effects, particularly in reducing inflammation and regulating microglial activity, warrant further investigation into its broader role in mitigating neuroinflammation and preserving microglial function in AD. [ABSTRACT FROM AUTHOR]

Objective and design: Neuroinflammation is a protective mechanism but can become harmful if chronic and/or unregulated, leading to neuronal damage and cognitive alterations. Limiting inflammation and promoting resolution could be achieved with nutrients such as grapes and blueberries polyphenols, saffron carotenoids, and omega-3, which have anti-inflammatory and proresolutive properties. Methods: This study explored the impact of 18-day supplementation with plant extracts (grape, blueberry and saffron), omega-3 or both (mix) on neuroinflammation induced by lipopolysaccharide (LPS, 250 µg/kg) in 149 mice at different time points post-LPS treatment (30 min, 2 h, 6 h). Inflammatory, oxidative and neuroprotective gene expression; oxylipin quantification; and fatty acid composition were analyzed at each time point. PCA analysis was performed with all these biomarkers. Results: Mix supplementation induced changes in the resolution of inflammation. In fact, the production of proinflammatory mediators in the hippocampus started earlier in the supplemented group than in the LPS group. Pro-resolving mediators were also found in higher quantities in supplemented mice. These changes were associated with increased hippocampal antioxidant status at 6 h post-LPS. Conclusions: These findings suggest that such dietary interventions with plant extracts, and omega-3 could be beneficial in preventing neuroinflammation and, consequently, age-related cognitive decline. Further research is needed to explore the effects of these supplements on chronic inflammation in the context of aging. [ABSTRACT FROM AUTHOR]

Caloric restriction (CR) has been proposed as a nutritional strategy to combat chronic diseases, including neurodegenerative diseases, as well as to delay aging. However, despite the benefits of CR, questions remain about its underlying mechanisms and cellular and molecular targets. Objective: As inflammatory processes are the basis or accompany chronic diseases and aging, we investigated the protective role of CR in the event of an acute inflammatory stimulus. Methods: Peripheral inflammatory and metabolic parameters were evaluated in Wistar rats following CR and/or acute lipopolysaccharide (LPS) administration, as well as glial changes (microglia and astrocytes), in two regions of the brain (hippocampus and hypothalamus) involved in the inflammatory response. We used a protocol of 30% CR, for 4 or 8 weeks. Serum and brain parameters were analyzed by biochemical or immunological assays. Results: Benefits of CR were observed during the inflammatory challenge, where the partial reduction of serum interleukin-6, mediated by CR, attenuated the systemic response. In the central nervous system (CNS), specifically in the hippocampus, CR attenuated the response to the LPS, as evaluated by tumor necrosis factor alpha (TNFα) levels. Furthermore, in the hippocampus, CR increased the glutathione (GSH) levels, resulting in a better antioxidant response. Discussion: This study contributes to the understanding of the effects of CR, particularly in the CNS, and expands knowledge about glial cells, emphasizing their importance in neuroprotection strategies. [ABSTRACT FROM AUTHOR]

Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPAR α is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPAR α signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPAR α levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPAR α up-regulates necroptosis signals in the intestinal organoids triggered by TNF- α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPAR α is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut–liver axis. Pparα deficiency in the ileum epithelium up-regulates necroptosis signals via TRIM38/TRIF and CREB3L3/MLKL pathways, leading to hepatic steatosis through the spread of gut-derived endotoxin. [Display omitted] [ABSTRACT FROM AUTHOR]

This study is aimed at exploring the potential mechanisms of melatonin (MT) in treating chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using network pharmacology and experimental study. The target genes of MT were acquired from the Swiss Target Prediction, SuperPred, SEA, and PharmMapper databases, and the CP/CPPS targets were collected based on OMIM, DisGeNET, and GeneCards databases. The intersection of MT and CP/CPPS target genes was analyzed. A PPI network was constructed using Cytoscape to identify core targets. The shared targets underwent GO and KEGG enrichment analyses by Using R software. Molecular docking of MT with core targets was performed using AutoDock and PyMOL. GROMACS software was used for molecular dynamics simulation. And using cell experiments to verify the potential effect of MT in CP/CPPS. Network pharmacology analysis reveals 284 shared targets between MT and CP/CPPS, with AKT1, SRC, HSP90AA1, PTGS2, BCL2L1, ALB, CASP3, NFKB1, HIF1A, and ESR1 identified as key targets. Enrichment analysis indicates that MT affects CP/CPPS through various biological processes, and pathway analysis emphasizes the significance of PI3K-Akt, MAPK, Ras, FoxO, HIF-1, EGFR, and apoptosis pathways. Molecular docking confirms strong binding between MT and core targets. It is worth noting that the molecular dynamics simulation showed that the average binding free energy of AKT1, PTGS2, ALB, HSP90AA1 proteins, and MT was − 26.15, − 29.48, − 18.59, and − 20.09 kcal/mol, respectively. These results indicated that AKT1, PTGS2, ALB, and HSP90AA1 proteins were strongly bound to MT. Cell experiments demonstrate that MT can inhibit the secretion of IL-1β, IL-6, and TNF-α in LPS-induced RWPE-1 cells, alleviate inflammation, and suppress cell apoptosis and oxidative stress. Network pharmacology, molecular docking, molecular dynamics simulation, and cell experiments showed that MT could play a role in CP/CPPS by regulating multiple targets and pathways. These findings provide an important scientific basis for further exploration of the molecular mechanism and clinical application of MT in CP/CPPS treatment and are expected to provide new ideas and directions for the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Periodontitis is a significant independent risk factor for atherosclerosis. Yet, the exact mechanism of action is still not fully understood. In this study, we investigated the effect of exosomes‐miR‐155‐5p derived from periodontal endothelial cells on atherosclerosis in vitro and in vivo. Higher expression of miR‐155‐5p was detected in the plasma exosomes of patients with chronic periodontitis (CP) and carotid atherosclerosis (CAS) compared to patients with CP. Also, the expression level of miR‐155‐5p was associated with the severity of CP. miR‐155‐5p‐enriched exosomes from HUVECs increased the angiogenesis and permeability of HAECs and promoted the expression of angiogenesis, permeability, and inflammation genes. Along with the overexpression or inhibition of miR‐155‐5p, the biological effect of HUVECs‐derived exosomes on HAECs changed correspondingly. In ApoE−/− mouse models, miR‐155‐5p‐enriched exosomes promoted the occurrence of carotid atherosclerosis by increasing permeable and angiogenic activity. Collectively, these findings highlight a molecular mechanism of periodontitis in CAS, uncovering exosomal miR‐155‐5p derived periodontitis affecting carotid endothelial cells in an 'exosomecrine' manner. Exosomal miR‐155‐5p may be used as a biomarker and target for clinical intervention to control this intractable disease in future, and the graphic abstract was shown in Figure S1. [ABSTRACT FROM AUTHOR]

The enzyme, insulin regulated aminopeptidase (IRAP), is expressed in multiple immune cells such as macrophages, dendritic cells and T cells, where it plays a role in regulating the innate and adaptive immune response. There is a genetic association between IRAP and survival outcomes in patients with septic shock where a variant of its gene was found to be associated with increased 28-day mortality. This study investigated the role for IRAP in a lipopolysaccharide (LPS)- induced inflammatory response which is thought to model facets of the systemic inflammation observed in the early stages of human gram-negative sepsis. The frequencies and activation of splenic immune cell populations were investigated in the IRAP knockout (KO) mice compared to the wildtype controls over a period of 4-, 24-, or 48-hours following LPS stimulation. Dendritic cells isolated from the spleen of female IRAP KO mice, displayed significant increases in the activation markers CD40, CD86 and MHCII at 24 hours after LPS induction. A modest heightened pro-inflammatory response to LPS was observed with increased expression of activation marker CD40 in M1 macrophages from male IRAP knockout mice. Observations in vitro in bone marrow-derived macrophages (BMDM) revealed a heightened pro-inflammatory response to LPS with significant increases in the expression of CD40 in IRAP deficient cells compared with BMDM from WT mice. The heightened LPS-induced response was associated with increased pro-inflammatory cytokine secretion in these BMDM cells. A genotype difference was also detected in the BMDM from female mice displaying suppression of the LPS-induced increases in the activation markers CD40, CD86, CD80 and MHCII in IRAP deficient cells. Thus, this study suggests that IRAP plays specific time- and sex-dependent roles in the LPS-induced inflammatory response in dendritic cells and macrophages. [ABSTRACT FROM AUTHOR]

It has remained yet unclear which soluble factors regulate the anti-inflammatory macrophage phenotype observed in both homeostasis and tumourigenesis. We show here that haptoglobin, a major serum protein with elusive immunoregulatory properties, binds and buffers bacterial lipopolysaccharides to attenuate activation of NFkB in macrophages. Haptoglobin binds different lipopolysaccharides with low micromolar affinities. Given its abundance, haptoglobin constitutes a buffer for serum-borne lipopolysaccharides, shielding them to safeguard against aberrant inflammatory reactions by reducing the amount of free lipopolysaccharides available for binding to TLR4. Concordantly, NFkB activation by haptoglobin-associated lipopolysaccharides was markedly delayed relative to stimulation with pure lipopolysaccharide. Our findings warrant evaluation of therapeutic benefits of haptoglobin for inflammatory conditions and re-evaluation of purification strategies. Finally, they allow to elucidate mechanisms of enhanced immunosuppression by oncofetal haptoglobin. [ABSTRACT FROM AUTHOR]

The study aims to compare the proinflammatory responses of colon epithelial cells to two potent virulence factors: lipopolysaccharide (LPS) from Pseudomonas aeruginosa and spike (S) protein of SARS-CoV-2. Both agents are known to induce significant inflammatory responses, leading to severe clinical manifestations.Human colon epithelial cells were treated with S protein and LPS at various time intervals (12, 24, 48, and 72 h). Cell viability was assessed, and the expression levels of key proinflammatory cytokines (IFN-γ, IL-1β, TNF-α, and IL-6) were measured using qRT-PCR. Statistical analyses were conducted to assess the data, incorporating t-tests and linear regression.The study found distinct patterns in cytokine expression in response to S protein and LPS. LPS treatment led to a rapid increase in cytokine expression at early time points (12 and 24 h), followed by a decline at later intervals. In contrast, S protein induced a more sustained proinflammatory response, with lower initial cytokine levels that persisted longer, particularly at 48 and 72 h.The differential proinflammatory responses observed between S protein and LPS treatments highlight their unique impacts on colon epithelial cells. Specifically, LPS induced an early but transient spike in cytokine levels, suggesting a rapid but short-lived inflammatory response. Conversely, the S protein triggered a prolonged inflammatory reaction, which may contribute to the persistent symptoms seen in COVID-19. The findings provide insights into the molecular mechanisms underlying inflammatory responses in bacterial and viral infections. Understanding these differences can inform therapeutic strategies for conditions like sepsis and COVID-19, leading to targeted treatments that mitigate excessive inflammation and improve patient outcomes. [ABSTRACT FROM AUTHOR]

The RNA binding protein Human Antigen R (HuR) has been identified as a main regulator of the innate immune response and its inhibition can lead to beneficial anti-inflammatory effects. To this aim, we previously synthesized a novel class of small molecules named Tanshinone Mimics (TMs) able to interfere with HuR-RNA binding, and that dampen the LPS-induced immune response. Herein, we present a novel series of TMs, encompassing thiophene 3/TM9 and 4/TM10, furan 5/TM11 and 6/TM12, pyrrole 7b/TM13, and pyrazole 8. The furan-containing 5(TM11) showed the greatest inhibitory effect of the series on HuR-RNA complex formation, as suggested by RNA Electromobility Shift Assay and Time-Resolved FRET. Molecular Dynamics Calculation of HuR − 5/TM11 interaction, quantum mechanics approaches and Surface Plasmon Resonance data, all indicates that, within the novel heteroaryl substituents, the furan ring better recapitulates the chemical features of the RNA bound to HuR. Compound 5/TM11 also showed improved aqueous solubility compared to previously reported TMs. Real-time monitoring of cell growth and flow cytometry analyses showed that 5/TM11 preferentially reduced cell proliferation rather than apoptosis in murine macrophages at immunomodulatory doses. We observed its effects on the innate immune response triggered by lipopolysaccharide (LPS) in macrophages, showing that 5/TM11 significantly reduced the expression of proinflammatory cytokines as Cxcl10 and Il1b. [ABSTRACT FROM AUTHOR]

A balanced inflammatory response is crucial for the organism to defend against external infections, however, an exaggerated response may lead to detrimental effects, including tissue damage and even the onset of disease. Therefore, anti-inflammatory drugs are essential for the rational control of inflammation. In this study, we found that a previously screened peptide TaY (KEKKEVVEYGPSSYGYG) was able to inhibit the LPS-induced RAW264.7 inflammatory response by decreasing a series of proinflammatory cytokines, such as TNF-α, IL-6, and nitric oxide (NO). To elucidate the underlying mechanism, we conducted further investigations. Western blot analysis showed that TaY reduced the phosphorylation of key proteins (IKK-α/β, IκB-α,NF-κB (P65)) in the TLR4-NF-κB signaling pathway and inhibited the inflammatory response. Furthermore, molecular docking and molecular dynamic simulations suggested that TaY binds to the hydrophobic pocket of MD2 through hydrogen bonding and hydrophobic interactions, potentially competing with LPS for MD2 binding. Collectively, TaY is a promising candidate for the development of novel therapeutic strategies against inflammatory disorders. [ABSTRACT FROM AUTHOR]

Background: Signal transducer and activator of transcription 3 (STAT3), a multifaceted transcription factor, modulates host immune responses by activating cellular response to signaling ligands. STAT3 has a pivotal role in the pathophysiology of kidney injury by counterbalancing resident macrophage phenotypes under inflammation conditions. However, STAT3's role in acute kidney injury (AKI), particularly in macrophage migration, and in chronic kidney disease (CKD) through fibrosis development, remains unclear. Methods: Stattic (a JAK2/STAT3 inhibitor, 5 mg/kg or 10 mg/kg) was administered to evaluate the therapeutic effect on LPS-induced AKI (L-AKI) and LPS-induced CKD (L-CKD), with animals sacrificed 6–24 h and 14 days post-LPS induction, respectively. The immune mechanisms of STAT3 blockade were determined by comparing the macrophage phenotypes and correlated with renal function parameters. Also, the transcriptomic analysis was used to confirm the anti-inflammatory effect of L-AKI, and the anti-fibrotic role was further evaluated in the L-CKD model. Results: In the L-AKI model, sequential increases in BUN and blood creatinine levels were time-dependent, with a marked elevation of 0–6 h after LPS injection. Notably, two newly identified macrophage subpopulations (CD11bhighF4/80low and CD11blowF4/80high), exhibited population changes, with an increase in the CD11bhighF4/80low population and a decrease in the CD11blowF4/80high macrophages. Corresponding to the FACS results, the tubular injury score, NGAL, F4/80, and p-STAT3 expression in the tubular regions were elevated. STAT3 inhibitor injection in L-AKI and L-CKD mice reduced renal injury and fibrosis. M2-type subpopulation with CD206 in CD11blowF4/80high population increased in the Stattic-treated group compared with that in the LPS-alone group in the L-AKI model. Additionally, STAT3 inhibitor reduced inflammation driven by LPS-stimulated macrophages and epithelial cells injury in the co-culture system. Transcriptomic profiling identified 3 common genes in the JAK-STAT, TLR, and TNF signaling pathways and 11 common genes in the LPS with macrophage response. The PI3K-AKT (IL-6, Akt3, and Pik3r1) and JAK-STAT pathways were determined as potential Stattic targets. Further confirmation through mRNA and protein expressions analyses showed that Stattic treatment reduced inflammation in the L-AKI and fibrosis in the L-CKD mice. Conclusions: STAT3 blockade effectively mitigated inflammation by retrieving the CD11blowF4/80high population, further emphasizing the role of STAT3-associated macrophage-driven inflammation in kidney injury. Plain English summary: This study investigated the role of STAT3 in LPS-induced acute kidney injury (AKI) and its prolonged pathophysiological effect. In a mouse model, blocking STAT3 with Stattic reduced inflammation and fibrosis, decreased the levels of inflammatory and extracellular matrix (ECM) substances, reduced the number of certain immune cells (macrophages), and influenced specific genes related to inflammation. The findings suggest that targeting STAT3 is a promising approach to treat AKI and CKD by controlling the inflammation and the immune response as well as ECM accumulation. This study provides novel insights into AKI and CKD progression and will facilitate the development of new treatments for kidney injuries at various stages. [ABSTRACT FROM AUTHOR]

Paraprobiotics and postbiotics represent a valid alternative to probiotic strains for ameliorating and preserving a healthy intestinal epithelial barrier (IEB). The present study investigated the effects of surface layer proteins (S-layer) of the dairy strain Lactobacillus helveticus ATCC® 15009™ (Lb ATCC® 15009™), as paraprobiotic, on the morpho-functional modulation of IEB in comparison to live or heat-inactivated Lb ATCC® 15009™ in an in vitro co-culture of Caco-2/HT-29 70/30 cells. Live or heat-inactivated Lb ATCC® 15009™ negatively affected transepithelial electrical resistance (TEER) and paracellular permeability, and impaired the distribution of Claudin-1, a tight junction (TJ) transmembrane protein, as detected by immunofluorescence (IF). Conversely, the addition of the S-layer improved TEER and decreased permeability in physiological conditions in co-cultures with basal TEER lower than 50 ohmcm2, indicative of a more permeable physiological IEB known as leaky gut. Transmission electron microscopy (TEM) and IF analyses suggested that the S-layer induces a structural TJ rearrangement and desmosomes' formation. S-layer also restored TEER and permeability in the presence of LPS, but not of a mixture of pro-inflammatory cytokines (TNF-α plus IFN-γ). IF analyses showed an increase in Claudin-1 staining when LPS and S-layer were co-administered with respect to LPS alone; in addition, the S-layer counteracted the reduction of alkaline phosphatase detoxification activity and the enhancement of pro-inflammatory interleukin-8 release both induced by LPS. Altogether, these data corroborate a paraprobiotic role of S-layer from Lb ATCC® 15009™ as a possible candidate for therapeutic and prophylactic uses in conditions related to gastrointestinal health and correlated with extra-intestinal disorders. [ABSTRACT FROM AUTHOR]

A total of 200 cattle of different ages, sexes, and breeds, suffering from respiratory symptoms, including 10 apparently healthy cattle, were examined clinically and bacteriologically for the isolation and identification of Histophilus somni. Enzyme-Linked Immunosorbent Assay (ELISA) was used to determine the levels of Bovine Interferon gamma (IFN-γ), Bovine Interleukin-4 (IL-4), and Immunoglobulin E (IgE) in the sera of the studied animals. Conventional bacteriological testing revealed that 25% (50/200) of the nasal swabs tested positive for H. somni. After culturing, the 16S rDNA and H. somni-specific PCR, gene sequencing, and phylogenetic analysis identified that 70% (35/50) of the isolates were confirmed to belong to Histophilus somni, with one isolate submitted to NCBI GenBank, receiving accession number OR100605. The seropositivity against H. somni LPS was estimated by an indirect ELISA test. The results showed that 35 (70%) of the cattle suffering from respiratory symptoms were seropositive for H. somni LPS. The LPS-specific IgE level, when compared between cattle with negative H. somni molecular results (0.429 ± 0.0139) and those with positive molecular results (0.733 ± 0.0227), showed a statistically significant (p < 0.05) increase in the mean Optical Density (OD) values. The association of IFN-γ and IL-4 with LPS-specific IgE antibodies was determined by indirect ELISA. The results indicated a significant (p < 0.05) increase in the mean IL-4 concentration in the sera of LPS-specific IgE seropositive cattle (200.151 ± 70.905) compared to seronegative animals (118.626 ± 27.642), with no statistically significant association (p > 0.05) between seropositivity and IFN-γ concentration. The results of this study suggest that H. somni LPS may induce a hypersensitized state in cattle. Additionally, this study suggests that Iraqi cattle may have elevated IgE levels against H. somni LPS. [ABSTRACT FROM AUTHOR]

This study investigates the impact of cooling rate and alloy composition on phase formations and properties of (CoCrCuTi)100−xFex (x = 0, 5, 10, 12.5, 15) high-entropy alloys (HEAs). Samples were synthesized using arc-melting and electromagnetic levitation, followed by quenching through the use of a Cu chill or V-shaped Cu mold. Cooling rates were evaluated by measuring dendrite arm spacings (DASs), employing the relation DAS = k ɛ−n, where constants k = 16 and n = ½. Without Fe addition, a microstructure consisting of BCC1 + BCC2 phases formed, along with an interdendritic (ID) FCC Cu-rich phase. However, with the addition of 5–10% Fe, a Cu-lean C14 Laves phase emerged, accompanied by a Cu-rich ID FCC phase. For cooling rates below 75 K/s, alloys containing 10% Fe exhibited liquid phase separation (LPS), characterized by globular Cu-rich structures within the Cu-lean liquid. In contrast, for the same composition, higher cooling rates of 400–700 K/s promoted a dendritic/interdendritic microstructure. Alloys with 12.5–15 at. % Fe displayed LPS irrespective of the cooling rate, although an increase in uniformity was noted at rates exceeding 700 K/s. Vickers hardness and fracture toughness generally increased with Fe content, with hardness ranging from 444 to 891 HV. The highest fracture toughness (5.5 ± 0.4 KIC) and hardness (891 ± 66 HV) were achieved in samples containing 15 at. % Fe, cooled at rates of 25–75 K/s. [ABSTRACT FROM AUTHOR]

Background: Immune stressors, such as lipopolysaccharides (LPS), profoundly affect microbiota balance, leading to gut dysbiosis. This imbalance disrupts the metabolic phenotype and structural integrity of the gut, increasing intestinal permeability. During puberty, a critical surge in estrogen levels is crucial for mammary gland development. However, inflammation originating from the gut in this period may interfere with this development, potentially heightening breast cancer risk later. The long‐term effects of pubertal inflammation on mammary development and breast cancer risk are underexplored. Such episodes can dysregulate cytokine levels and microRNA expression, altering mammary cell gene expression, and predisposing them to tumorigenesis. Methods: This study hypothesizes that prebiotics, specifically Lentinula edodes Cultured Extract (AHCC), can counteract LPS's adverse effects. Using BALB/c mice, an acute LPS dose was administered at puberty, and breast cancer predisposition was assessed at 13 weeks. Cytokine and tumor‐related microRNA levels, tumor development, and cancer stem cells were explored through immunoassays and qRT‐PCR. Results: Results show that LPS induces lasting effects on cytokine and microRNA expression in mammary glands and tumors. AHCC modulates cytokine expression, including IL‐1β, IL‐17A/F, and IL‐23, and mitigates LPS‐induced IL‐6 in mammary glands. It also regulates microRNA expression linked to tumor progression and suppression, particularly counteracting the upregulation of oncogenic miR‐21, miR‐92, and miR‐155. Although AHCC slightly alters some tumor‐suppressive microRNAs, these changes are modest, highlighting a complex regulatory role that warrants further study. Conclusion: These findings underscore the potential of dietary interventions like AHCC to mitigate pubertal LPS‐induced inflammation on mammary gland development and tumor formation, suggesting a preventive strategy against breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometritis is a prevalent disease in perinatal dairy cows, which leads to compromised reproductive function. Studies have confirmed that A20, also known as TNFAIP3, can regulate inflammatory responses in various cells. However, it remains unclear whether A20 regulates the inflammatory response of bovine endometrial cells and if autophagy plays a role in A20's regulation of inflammatory responses. In this paper, we show that elevated expression of A20 is linked to the progression of endometritis in dairy cows. A20 inhibited the activation of the NF-κB pathway and the mRNA expression levels of proinflammatory cytokines in LPS-induced bovine endometrial epithelial cells. Moreover, it enhanced autophagic activity in the bovine endometrial epithelial cells inhibited by LPS. Our study further showed that A20 mitigated the inflammatory response of bovine endometrial epithelial cells by promoting autophagy. These findings will enhance our understanding of the pathogenesis and provide novel insights for the prevention and treatment of endometritis in dairy cows. Endometritis represents a prevalent condition in perinatal dairy cows. Bovine endometrial epithelial cells (BEECs), as the primary interface between cavity and the external environment, are particularly vulnerable to infection by pathogenic bacteria following parturition. A20 is essential for regulating inflammation and modulating immune responses. Nevertheless, the exact role of A20 in the BEECs in response to inflammatory response is not fully understood. An endometritis model infected by Escherichia coli (E. coli) in vivo and a BEECs inflammation model induced with lipopolysaccharide (LPS) in vitro were built to investigate the function and governing mechanisms of A20 in endometritis. The results showed that infection with E. coli resulted in endometrial damage, inflammatory cell infiltration, and upregulation of inflammatory factors in dairy cows. Furthermore, A20 expression was upregulated in the endometrium of cows with endometritis and in BEECs following LPS stimulation. A20 overexpression attenuated the level of proinflammatory cytokines in LPS-stimulated BEECs; conversely, A20 knockdown lead to an exacerbated response to LPS stimulation. The overexpression of A20 was shown to activate autophagy and suppress the NF-κB signaling pathway in LPS-stimulated BEECs. However, blocking autophagy with chloroquine notably attenuated the anti-inflammatory effect of A20, leading to the activation of the NF-κB signaling pathway. In summary, the study demonstrated that A20's suppression of inflammation in LPS-stimulated BEECs is associated with the activation of autophagy. Therefore, the A20 protein showed potential as a novel treatment focus for managing endometritis in dairy cows. [ABSTRACT FROM AUTHOR]

Simple Summary: The salmonid industry is susceptible to opportunistic pathogens particularly affecting fish in early developmental stages. Understanding the immunological capacity during these stages is crucial for effective disease control. The receptor for Interleukin 8 (CXCR1), plays a key role in various inflammatory conditions. This study analyzed the expression of IL-8R and IL8 in rainbow trout larvae in response to bacterial lipopolysaccharide (LPS). The larvae 19 day post-hatching (dph) exhibited strong immune responses after 8 h of LPS stimulation, with IL-8 and omCXCR1 protein expression increasing. The use of specific antisera allowed localization of both proteins in mucosal tissue cells. This study highlights the effectiveness of LPS immersion in activating the innate immune system of trout larvae using IL-8/CXCR1 as immunological markers. The salmonid industry faces challenges due to the susceptibility of fish to opportunistic pathogens, particularly in early developmental stages. Understanding the immunological capacity during these stages is crucial for developing effective disease control strategies. IL-8R, a member of the G-protein-coupled receptor family, acts as a receptor for Interleukin 8 (IL-8). The binding of IL-8 to IL-8R plays a major role in the pathophysiology of a wide spectrum of inflammatory conditions. This study focused on the immune response capacity of rainbow trout (Oncorhynchus mykiss) larvae by analyzing IL-8/CXCR1 response to lipopolysaccharide (LPS) from Pseudomonas aeruginosa. Previous research demonstrated that LPS from P. aeruginosa acts as a potent immunostimulant in teleost, enhancing pro-inflammatory cytokines. The methodology included in silico analysis and the synthesis and characterization of an omCXCR1-derived epitope peptide, which was used to produce omCXCR1-specific anti98 serum in mice. The research revealed that rainbow trout larvae 19 days post-hatching (dph) exhibited pronounced immune responses post-stimulation with 1 µg/mL of LPS. This was evidenced by the upregulated protein expression of IL-8 and omCXCR1 in trout larvae 2 and 8 h after LPS challenge, as analyzed by ELISA and immunohistochemistry. Furthermore, fluorescence microscopy successfully revealed the colocalization of IL-8 and its receptor in cells from mucosal tissues after LPS challenge in larvae 19 dph. These findings underscore the efficacy of LPS immersion as a method to activate the innate immune system in trout larvae. Furthermore, we propose IL-8 and its receptor as molecular markers for evaluating immunostimulation in the early developmental stages of salmonids. [ABSTRACT FROM AUTHOR]

Sprint performance is commonly assessed via discrete sprint tests and analyzed through kinematic estimates modeled using a mono-exponential equation, including estimated maximal sprinting speed ( M S S ), relative acceleration ( T A U ), maximum acceleration ( M A C ), and relative propulsive maximal power ( P M A X ). The acceleration–velocity profile (AVP) provides a simple summary of short sprint performance using two parameters: MSS and MAC, which are useful for simplifying descriptions of sprint performance, comparison between athletes and groups of athletes, and estimating changes in performance over time or due to training intervention. However, discrete testing poses logistical challenges and defines an athlete's AVP exclusively from the performance achieved in an isolated testing environment. Recently, an in situ AVP (velocity–acceleration method) was proposed to estimate kinematic parameters from velocity and acceleration data obtained via global or local positioning systems (GPS/LPS) over multiple training sessions, plausibly improving the time efficiency of sprint monitoring and increasing the sample size that defines the athlete's AVP. However, the validity and sensitivity of estimates derived from the velocity–acceleration method in relation to changes in criterion scores remain elusive. To assess the concurrent validity and sensitivity of kinematic measures from the velocity–acceleration method, 31 elite youth basketball athletes (23 males and 8 females) completed two maximal effort 30 m sprint trials. Performance was simultaneously measured by a laser gun and an LPS (Kinexon), with kinematic parameters estimated using the time–velocity and velocity–acceleration methods. Agreement ( % B i a s ) between laser gun and LPS-derived estimates was within the practically significant magnitude ( ± 5%), while confidence intervals for the percentage mean absolute difference ( % M A D ) overlapped practical significance for T A U , M A C , and P M A X using the velocity–acceleration method. Only the M S S parameter showed a sensitivity ( % M D C 95 ) within practical significance (<5%), with all other parameters showing unsatisfactory sensitivity (>10%) for both the time–velocity and velocity–acceleration methods. Thus, sports practitioners may be confident in the concurrent validity and sensitivity of M S S estimates derived in situ using the velocity–acceleration method, while caution should be applied when using this method to infer an athlete's maximal acceleration capabilities. [ABSTRACT FROM AUTHOR]

Curcumin (Cur), the primary curcuminoid found in Curcuma longa L., has garnered significant attention for its potential anti-inflammatory and antibacterial properties. However, its hydrophobic nature significantly limits its bioavailability. Additionally, adipose-derived stem cells (ADSCs) possess immunomodulatory properties, making them useful for treating inflammatory and autoimmune conditions. This study aims to verify the efficacy of poly(ε-caprolactone) nanocapsules (NCs) in improving Cur's bioavailability, antibacterial, and immunomodulatory activities. The Cur-loaded nanocapsules (Cur-NCs) were characterized for their physicochemical properties (particle size, polydispersity index, Zeta potential, and encapsulation efficiency) and stability over time. A digestion test simulated the behavior of Cur-NCs in the gastrointestinal tract. Micellar phase analyses evaluated the Cur-NCs' bioaccessibility. The antibacterial activity of free Cur, NCs, and Cur-NCs against various Gram-positive and Gram-negative strains was determined using the microdilution method. ADSC viability, treated with Cur-NCs and Cur-NCs in the presence or absence of lipopolysaccharide, was analyzed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay. Additionally, ADSC survival was assessed through the Muse apoptotic assay. The expression of both pro-inflammatory (interleukin-1β and tumor necrosis factor-α) and anti-inflammatory (IL-10 and transforming growth factor-β) cytokines on ADSCs was evaluated by real-time polymerase chain reaction. The results demonstrated high stability post-gastric digestion of Cur-NCs and elevated bioaccessibility of Cur post-intestinal digestion. Moreover, Cur-NCs exhibited antibacterial activity against Escherichia coli without affecting Lactobacillus growth. No significant changes in the viability and survival of ADSCs were observed under the experimental conditions. Finally, Cur-NCs modulated the expression of both pro- and anti-inflammatory cytokines in ADSCs exposed to inflammatory stimuli. Collectively, these findings highlight the potential of Cur-NCs to enhance Cur's bioavailability and therapeutic efficacy, particularly in cell-based treatments for inflammatory diseases and intestinal dysbiosis. [ABSTRACT FROM AUTHOR]

Objective and design: This observational study investigated the regulatory mechanism of Pim-1 in inflammatory signaling pathways. Materials: THP-1, RAW 264.7, BV2, and Jurkat human T cell lines were used. Treatment: None. Methods: Lipopolysaccharide (LPS) was used to induce inflammation, followed by PIM1 knockdown. Western blot, immunoprecipitation, immunofluorescence, and RT-PCR assays were used to assess the effect of PIM1 knockdown on LPS-induced inflammation. Results: PIM1 knockdown in macrophage-like THP-1 cells suppressed LPS-induced upregulation of pro-inflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase-2, phosphorylated Janus kinase, signal transducer and activator of transcription 3, extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and nuclear factor kappa B p65 (NF-κB p65). It also suppressed upregulation of inhibitor of NF-κB kinase α/β and enhanced the nuclear translocation of NF-κB p65. Moreover, it inhibited the upregulation of Nod-like receptor family pyrin domain-containing 3 (NLRP3) and cleavage of caspase-1 induced by co-treatment of LPS with adenosine triphosphate. Additionally, p-transforming growth factor-β-activated kinase 1 (TAK1) interacted with Pim-1. All three members of Pim kinases (Pim-1, Pim-2, and Pim-3) were required for LPS-mediated inflammation in macrophages; however, unlike Pim-1 and Pim-3, Pim-2 functioned as a negative regulator of T cell activity. Conclusions: Pim-1 interacts with TAK1 in LPS-induced inflammatory responses and is involved in MAPK/NF-κB/NLRP3 signaling pathways. Additionally, considering the negative regulatory role of Pim-2 in T cells, further in-depth studies on their respective functions are needed. [ABSTRACT FROM AUTHOR]

Objective: Inulicin is a sesquiterpene lactone in Inulae Flos which is clinically used for the treatment of inflammatory diseases, such as cough, sputum production, and vomiting. This study aimed to demonstrate the anti-inflammatory activity and the underlying mechanism of inulicin by using lipopolysaccharide (LPS)-induced in vitro and in vivo models. Methods: LPS-stimulated RAW264.7 macrophages and mouse peritoneal macrophages (MPMs) were used for evaluating the in vitro anti-inflammatory activity of inulicin, while endotoxemia mice were used for evaluating its in vivo action. Cytokines' levels were determined by ELISA. RT-qPCR and western blot were used for assaying the mRNA and protein levels of target genes. RAW264.7 macrophages transfected with reporter plasmid pNFκB-TA-luc or pAP1-TA-luc were used for assaying the activation of NF-κB or AP-1 signaling. Results: Inulicin significantly inhibited LPS-induced production of NO, IL-6, c-c motif chemokine ligand 2 (CCL2), and IL-1β in both RAW264.7 cells and MPMs. Mechanism study indicated that it could suppress inducible nitric oxide synthase, IL-6, CCL2, and IL-1β mRNA levels in LPS-stimulated RAW264.7 cells. Moreover, inulicin inhibited IκBα phosphorylation and prevented the nuclear translocation of p65, thereby inactivating NF-κB signaling. Concurrently, it also inhibited AP-1 signaling by reducing the phosphorylation of C-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). In endotoxemia mice, a single intraperitoneal administration of inulicin could decrease the production of pro-inflammatory cytokines in serum and peritoneal lavage fluid. Conclusions: The present study demonstrates that inulicin possesses anti-inflammatory effects in vitro and in vivo, which suggests that inulicin might be a promising candidate for the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Intestinal inflammation is one of the main health challenges affecting the quality of life of millions of people worldwide. Accumulating evidence introduces several flavonoids with multifaceted therapeutic properties in inflammatory diseases including intestinal inflammation. Herein, we examined potential anti-inflammatory properties of 5,4'-dihydroxy-6,8-dimethoxy7-O-rhamnosylflavone (DDR) flavone derived from Indigofera aspalathoides Vahl (I. aspalathoides Vahl) on lipopolysaccharide (LPS)-induced intestinal inflammation and injury in mice. Oral DDR treatment decreased serum levels of pro-inflammatory cytokines including TNF-α, IL-6, and IL-1β. It reduced oxidative stress through augmenting the activities of catalase (CAT) and superoxide dismutase (SOD) and reducing the level of malondialdehyde (MDA) in the duodenum and colon tissues. Moreover, DDR enhanced the activities of digestive enzymes including trypsin, pancreatic lipase, and amylase, and increased the production of short-chain fatty acids (SCFAs) by colon microbiota. Histopathological investigation of duodenum and colon revealed that DDR inhibited inflammatory infiltration and largely restored mucosal architecture and protected lining integrity. Importantly, DDR suppressed activation of nuclear factor-κB (NF-κB) signaling pathway through reduced expression of Toll-like receptor 4 (TLR4) and expression and phosphorylation of P65. The current study identified DDR as anti-inflammatory flavonoid capable of ameliorating LPS-induced intestinal inflammation through suppression of NF-κB signaling. [ABSTRACT FROM AUTHOR]

B cell initial activity is regulated through a balance of activation and suppression mediated by regulatory molecules expressed in B cells; however, the molecular mechanisms underlying this process remain incompletely understood. In this study, we investigated the function of the Fc receptor-like (Fcrl) family molecule Fcrl5, which is constitutively expressed in naive B cells, in humoral immune responses. Our study demonstrated that B cell-specific overexpression of Fcrl5 enhanced antibody (Ab) production in both T cell-independent type 1 (TI1) and T cell-dependent (TD) responses. Additionally, it promoted effector B cell formation under competitive conditions in TD responses. Mechanistically, in vitro ligation of Fcrl5 by agonistic Abs reduced cell death and enhanced proliferation in lipopolysaccharide-stimulated B cells. In the presence of anti-CD40 Abs and IL-5, the Fcrl5 ligation not only suppressed cell death but also enhanced differentiation into plasma cells. These findings reveal a novel role of Fcrl5 in promoting humoral immune responses by enhancing B cell viability and plasma cell differentiation. [ABSTRACT FROM AUTHOR]

Drug-loaded non-resorbable polymeric nanoparticles (NPs) are proposed as an adjunctive treatment for pulp regenerative strategies. The present in vitro investigation aimed to evaluate the effectiveness of tideglusib-doped nanoparticles (TDg-NPs) in mitigating the adverse effects of bacterial lipopolysaccharide endotoxin (LPS) on the viability, morphology, migration, differentiation and mineralization potential of human dental pulp stem cells (hDPSCs). Cell viability, proliferation, and differentiation were assessed using a MTT assay, cell migration evaluation, cell cytoskeleton staining analysis, Alizarin Red S staining and expression of the odontogenic related genes by a real-time quantitative polymerase chain reaction (RT-qPCR) were also performed. Cells were tested both with and without stimulation with LPS at various time points. One-way ANOVA and Tukey's test were employed for statistical analysis (p < 0.05). Adequate cell viability was encountered in all groups and at every tested time point (24, 48, 72 and 168 h), without differences among the groups (p > 0.05). The analysis of cell cytoskeleton showed nuclear alteration in cultures with undoped NPs after LPS stimulation. These cells exhibited an in blue diffuse and multifocal appearance. Some nuclei looked fragmented and condensed. hDPSCs after LPS stimulation but in the presence of TDg-NPs exhibited less nuclei changes. LPS induced down-regulation of Alkaline phosphatase, Osteonectin and Collagen1 gene markers, after 21d. LPS half-reduced the cells production of calcium deposits in all groups (p < 0.05), except in the group with TDg-NPs (decrease about 10 %). LPS induced lower mineral deposition and cytoskeletal disorganization in hDPSCs. These effects were counteracted by TDg-NPs, enhancing osteogenic differentiation and mineralization. [Display omitted] • LPS induced in hDPSCs lower mineral deposition. • LPS produces in hDPSCs cytoskeletal disorganization. • Tideglusib counteracts LPS adverse effect on hDPSCs. • Tideglusib enhances mineralization ability of hDPSCs. [ABSTRACT FROM AUTHOR]

Omega-3 (n3) is a polyunsaturated fatty acid well known for its anti-inflammatory and neuroprotective properties. Obesity is linked to chronic inflammation that disrupts metabolism, the intestine physiology and the central nervous system functioning. This study aims to determine if n3 supplementation can interfere with the effects of obesity on the mitochondrial activity, intestinal barrier, and neurotransmitter levels in the brain of Wistar rats that received cafeteria diet (CAF). We examined adipose tissue, skeletal muscle, plasma, intestine, and the cerebral cortex of four groups: CT (control diet), CTn3 (control diet with n3 supplementation), CAF, and CAFn3 (CAF and n3). Diets were offered for 13 weeks, with n3 supplementation in the final 5 weeks. Adipose tissue Electron Transport Chain complexes I, II, and III showed higher activity in CAF groups, as did complexes III and IV in skeletal muscle. Acetate levels in plasma were reduced in CAF groups, and Lipopolysaccharide (LPS) was higher in the CAF group but reduced in CAFn3 group. Claudin-5 in the intestine was lower in CAF groups, with no n3 supplementation effect. In the cerebral cortex, dopamine levels were decreased with CAF, which was reversed by n3. DOPAC, a dopamine metabolite, also showed a supplementation effect, and HVA, a diet effect. Serotonin levels increased in the CAF group that received supplementation. Therefore, we demonstrate disturbances in mitochondria, plasma, intestine and brain of rats submitted to CAF and the potential benefit of n3 supplementation in endotoxemia and neurotransmitter levels. [ABSTRACT FROM AUTHOR]

Depression is a debilitating mood disorder that causes persistent feelings of sadness, emptiness, and a loss of joy. However, the clinical efficacy of representative drugs for depression, such as selective serotonin reuptake inhibitors, remains controversial. Therefore, there is an urgent need for more effective therapies to treat depression. Neuroinflammation and the hypothalamic-pituitary-adrenal (HPA) axis are pivotal factors in depression. Inulae Flos (IF), the flower of Inula japonica Thunb, is known for its antioxidant and anti-inflammatory effects. This study explored whether IF alleviates depression in both in vitro and in vivo models. For in vitro studies, we treated BV2 and PC12 cells damaged by lipopolysaccharides or corticosterone (CORT) with IF to investigate the mechanisms of depression. For in vivo studies, C57BL/6 mice were exposed to chronic restraint stress and were administered IF at doses of 0, 100, and 300 mg/kg for 2 weeks. IF inhibited pro-inflammatory mediators, such as nitric oxide, inducible nitric oxide synthase, and interleukins in BV2 cells. Moreover, IF increased the viability of CORT-damaged PC12 cells by modulating protein kinase B, a mammalian target of the rapamycin pathway. Behavioral assessments demonstrated that IF reduced depression-like behaviors in mice. We found that IF reduced the activation of microglia and astrocytes, and regulated synapse plasticity in the mice brains. Furthermore, IF lowered elevated CORT levels in the plasma and restored glucocorticoid receptor expression in the hypothalamus. Collectively, these findings suggest that IF can alleviate depression by mitigating neuroinflammation and recovering dysfunction of the HPA-axis. [ABSTRACT FROM AUTHOR]