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ApoB insertion/deletion (ins/del) genetic variant (rs11279109) is thought to be related to cardio-metabolic markers and obesity. This association has the potential to be modified by dietary patterns. Since the majority of studies concerned the role of dietary acid load (DAL) or ApoB in type 2 diabetes mellitus (T2DM) and its complications independently, and due to the insufficient data regarding the possible interactions between ApoB genetic variants and DAL on anthropometric and metabolic markers, we aimed to study the interaction between this genetic variant and dietary acid load (DAL) on cardio-metabolic markers, along with leptin among Iranian individuals with T2DM. 700 T2DM patients were randomly recruited. A validated semi-quantitative food frequency questionnaire was used for DAL calculation including potential renal acid load (PRAL) and net-endogenous acid production (NEAP). The polymerase chain reaction was used for genotyping the ApoB ins/del (rs11279109). The general linear model was applied to find the interactions in the crude and adjusted models. Patients with del/del genotype (rs11279109) with high PRAL intake have lower low-density lipoprotein cholesterol (LDL-C) (Pinteraction = 0.004), LDL/HDL ratio (Pinteraction = 0.02), total cholesterol (TC) (Pinteraction = 0.04), triglyceride (TG) (Pinteraction = 0.04), leptin (Pinteraction = 0.04) and interleukin-18 (IL-18) (Pinteraction = 0.04). Moreover, the interaction of gene and DAL in the PRAL method on TG concentration (P = 0.04), waist circumference (WC) (P = 0.04), and LDL/HDL ratio (P = 0.04) were significant. Eventually, a positive relationship was observed between the presence of the del/del genotype (rs11279109) and higher levels of TG, TC, LDL-C, IL-18, and LDL/HDL, in individuals with lower adherence to DAL, after adjusting for various covariates. Further studies are needed to investigate and confirm these findings. [ABSTRACT FROM AUTHOR]

The spinal muscular atrophy (SMA) phenotype strongly correlates with the SMN2 gene copy number. However, the severity and progression of the disease vary widely even among affected individuals with identical copy numbers. This study aimed to investigate the impact of genetic variability in oxidative stress, inflammatory, and neurodevelopmental pathways on SMA susceptibility and clinical progression. Genotyping for 31 genetic variants across 20 genes was conducted in 54 SMA patients and 163 healthy controls. Our results revealed associations between specific polymorphisms and SMA susceptibility, disease type, age at symptom onset, and motor and respiratory function. Notably, the TNF rs1800629 and BDNF rs6265 polymorphisms demonstrated a protective effect against SMA susceptibility, whereas the IL6 rs1800795 was associated with an increased risk. The polymorphisms CARD8 rs2043211 and BDNF rs6265 were associated with SMA type, while SOD2 rs4880, CAT rs1001179, and MIR146A rs2910164 were associated with age at onset of symptoms after adjustment for clinical parameters. In addition, GPX1 rs1050450 and HMOX1 rs2071747 were associated with motor function scores and lung function scores, while MIR146A rs2910164, NOTCH rs367398 SNPs, and GSTM1 deletion were associated with motor and upper limb function scores, and BDNF rs6265 was associated with lung function scores after adjustment. These findings emphasize the potential of genetic variability in oxidative stress, inflammatory processes, and neurodevelopmental pathways to elucidate the complex course of SMA. Further exploration of these pathways offers a promising avenue for developing personalized therapeutic strategies for SMA patients. [ABSTRACT FROM AUTHOR]

This study aimed to explore the potential association between Endothelin type A receptor (EDNRA) genetic polymorphisms and susceptibility to large artery atherosclerotic stroke (LAA), as well as the involvement of inflammation mechanisms. We recruited Han Chinese patients with LAA and age- and sex-matched controls. The distribution of alleles and genotypes for 16 single nucleotide polymorphisms (SNPs) in EDNRA was analyzed using dominant, recessive, and co-dominant genetic models between cases and controls. We quantified the mRNA and protein levels of EDNRA and NLRP3 genes, and concentrations of inflammatory factors (TNFα, IL-1β, IL-6, IL-8, IL-10, IL-18, and CCL18) in peripheral blood samples randomly selected from cases and controls. We also investigated the relationship between these SNPs, gene expression patterns and inflammatory factor levels. A total of 428 LAA cases and 434 controls were enrolled in this study. The results showed that rs5343 TT genotype of EDNRA was significantly associated with an increased risk of LAA (OR = 3.243, 95%CI = 1.608–6.542, P = 0.001). It also demonstrated a significant upregulation level of NLRP3 as well as higher concentrations of IL-10, IL-18, and CCL-18 in cases compared to controls. Besides, we discovered that the EDNRA polymorphisms were linked to NLRP3, IL-6, IL-10, and IL-18 levels in cases. There existed a positive correlation between EDNRA transcription levels and both NLRP3 transcript levels (r = 0.437, p < 0.001) and IL-18 concentrations (r = 0.212, p < 0.001). EDNRA is linked to susceptibility of LAA. This association may be attributed to the NLRP3-mediated inflammatory pathway. [ABSTRACT FROM AUTHOR]

Some drugs or chemicals exhibit different safety profiles in newborns/young children compared to adults. Polyhexamethyleneguanidine phosphate (PHMG-P) has been implicated in the humidifier disinfectant tragedy in 2011. There are limited reports on the toxicity of PHMG-P in neonatal animals. This study aimed to assess the toxicity of PHMG-P in neonates and to compare toxicity between young and adult mice. Mice aged 7–10 days and 8 weeks were anesthetized with isoflurane and then intranasally instilled with 0.9 mg/kg and 1.5 mg/kg PHMG-P once weekly for 4 weeks. The control group was given a corresponding volume of saline intranasally. Approximately 20 h after the 4th instillation, all mice (juveniles aged 28‒31 days and adults aged 11 weeks) were euthanized. Assessments included body weights, organ weights, cytokine production, and histopathological examinations. Both juvenile and adult mice exhibited significant pulmonary toxicity. There were no significant changes in body weight in either male or female juveniles, whereas adult mice experienced 5.0‒22.2% weight loss. However, lung weights increased in both age groups, accompanied by rises in cytokines and chemokines. Histopathological analyses revealed significant lung changes in both juvenile and adult mice, including immune cell infiltration, foamy macrophage, and granulomatous inflammation. PHMG-P is known to cause inflammation and fibrotic changes in rodents and humans that persist even during long recovery periods. Further research is required to explore the long-term health effects of PHMG-P following repeated early-life exposure. [ABSTRACT FROM AUTHOR]

CXCL13 is a chemokine that plays an important role in the regulation and development of secondary lymphoid organs. CXCL13 is also involved in the regulation of pathological processes, particularly inflammatory responses, of many diseases. The function of CXCL13 varies depending on the condition of the host. In a healthy condition, CXCL13 is mainly secreted by mouse stromal cells or human follicular helper T cells, whereas in diseases conditions, they are produced by human peripheral helper T cells and macrophages in non-lymphoid tissues; this is termed ectopic expression of CXCL13. Ectopic CXCL13 expression is involved in the pathogenesis of various immune-mediated inflammatory diseases as it regulates the migration of B lymphocytes, T lymphocytes, and other immune cells in inflammatory sites as well as influences the expression of inflammatory factors. Additionally, ectopic expression of CXCL13 plays a key role in ectopic lymphoid organ formation. In this review, we focused on the sources of CXCL13 in different conditions and its regulatory mechanisms in immune-mediated inflammatory diseases, providing novel ideas for further research on targeting CXCL13 for the treatment of immune-mediated inflammatory diseases. [ABSTRACT FROM AUTHOR]

Obesity is a serious global health issue. Emerging evidence indicates that the gut microbiota may contribute to the development of obesity, possibly by instigating inflammatory processes. The objective of this research is to conduct a comparative analysis of the gut microbiota composition in obese and normal-weight Uygur adults, while examining the associations with adipocyte-related factors and dietary variables. According to the inclusion and exclusion criteria, twenty-seven Uygur adults with obesity and twenty Uygur adults with normal-weight were recruited from a local community. Anthropometric measurements and blood samples were collected. Gut microbiota composition was analyzed using 16 S rRNA gene sequencing. Adipocyte-related factors were measured using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed to compare the gut microbiota composition between the two groups and to identify correlations between gut microbiota and adipocyte-related factors. Compared with the normal-weight group, the obese group exhibited a marked reduction in both diversity and richness of the gut microbiota, alongside a decrease in Ruminococcaceae_UCG_014, Coprococcus_2, and Parabacteroides, and an increase in Megamonas and Lachnoclostridium, implying a potential link to the development of obesity. Individuals with obesity were found to have higher Leptin (LEP), Interleukin-6 (IL-6), and C-reactive protein (CRP) than normal-weight individuals. Obese Uygur adults exhibited a gut microbiota characterized by diminished diversity and richness relative to normal-weight individuals. Parabacteroides, Megamonas, and Lachnoclostridium may play an important role in the development of obesity in Uygur population. Underlying mechanisms need further investigation. [ABSTRACT FROM AUTHOR]

Septic lung injury is strongly associated with polarization of M1 macrophages and excessive cytokine release. Fibroblast growth factor (FGF) signaling plays a role in both processes. However, the impact of FGF2 deficiency on macrophage polarization and septic acute lung injury remains unclear. To investigate this, we obtained macrophages from FGF2 knockout mice and examined their polarization and inflammatory cytokine expression. We also eliminated endogenous macrophages using clodronate liposomes and administered FGF2 knockout or WT macrophages intravenously in conjunction with cecal ligation and puncture (CLP) surgery to induce sepsis. In vitro analysis by flow cytometry and real-time PCR analysis demonstrated that FGF2 deficiency resulted in increased expression of M1 markers (iNOS and CD86) and inflammatory cytokines (CXCL1, IL1β, and IL6), especially after LPS stimulation. Additionally, immunofluorescence demonstrated increased nuclear translocation of p65 NF-κB in FGF2 knockout macrophages and RNA-seq analysis showed enrichment of differentially expressed genes in the IL17 and TNFα inflammatory signaling pathways. Furthermore, in vivo experiments revealed that depletion of FGF2 in macrophages worsened sepsis-induced lung inflammation, lung vascular leak, and lung histological injury, accompanied by an increase in CD86-positive cells and apoptosis. Our study suggests that FGF2 deficiency in macrophages plays a critical role in the pathogenesis of septic ALI, possibly because of the enhanced M1 macrophage polarization and production of proinflammatory cytokines. These findings provide empirical evidence for potential therapeutic interventions targeting FGF2 signaling to modulate the polarization of M1 and M2 macrophages in the management of sepsis-induced acute lung injury. [ABSTRACT FROM AUTHOR]

Although Alzheimer's disease (AD) and intracranial aneurysm (IA) were two different types of diseases that occurred in the brain, ruptured IA (RIA) survivors may experience varying degrees of cognitive dysfunction. Neither AD nor IA is easily recognizable by an early onset so that the incidence of adverse clinical outcomes would be on the rise. Therefore, we focused on the exploration of the shared genes and molecular mechanisms between AD and IA, which would be significant for the efficiency of co-screening and co-diagnosis. Two GEO datasets were selected for the weighted gene co-expression network analysis (WGCNA) and differentially expressed gene screening, obtaining 78 overlapped genes. Next, 9 hub genes were identified by the protein-protein interaction network, including PIK3CA, GAB1, IGF1R, PLCB1, PGR, PDGFRB, PLCE1, FGFR3, and SYNJ1. The interactions among the hub genes, miRNA, and TFs were also explored. Meanwhile, we performed GO and KEGG pathway enrichment analyses for the results of WGCNA and hub genes, which showed that the Ras signaling and Rap1 signaling were the main shared pathogenesis. In conclusion, the present bioinformatics analysis revealed that AD and IA had the shared genes and molecular mechanisms, and these outcomes were associated with inflammation and calcium homeostasis, which could provide research clues for further studies. [ABSTRACT FROM AUTHOR]

The C-reactive protein-albumin-lymphocyte (CALLY) index, which integrates albumin, lymphocytes, and C-reactive protein levels, has emerged as a novel method to assess nutritional and inflammatory statuses in patients. This study examined the correlation between the CALLY index and sarcopenia risk using two cohorts: 1804 community dwellers from the NHANES database in the United States and 139 patients from the Department of Gerontology at Kunshan Hospital, China. In the US community cohort, RCS curve analysis was used to examine the non-linear relationship between inflammatory/nutritional markers and sarcopenia, subgroup analysis was also conducted. Logistic regression was employed to evaluate the association between the CALLY index and the risk of sarcopenia in both cohorts. Results demonstrated a significant non-linear relationship between the CALLY index and the risk of sarcopenia (P < 0.001). Elevated levels of the CALLY index are independently linked to a decreased risk of sarcopenia in both community residents (OR = 0.35, 95% CI 0.20–0.57, Q3 CALLY index and OR = 0.26, 95% CI 0.11–0.56, Q4 CALLY index) and hospitalized patients (OR = 0.35, 95% CI 0.12–0.96). This finding identified low CALLY index as a conveniently measurable parameter, serving as a nutritional and inflammatory risk factor for sarcopenia. [ABSTRACT FROM AUTHOR]

Urate-lowering treatment (ULT) to target with xanthine oxidase inhibitors (XOIs) paradoxically causes early increase in gouty arthritis flares. Because delayed reduction in flare burden is mechanistically unclear, we tested for ULT inflammation responsiveness markers. Unbiased proteomics analyzed blood samples (baseline, 48 weeks ULT) in two, independent ULT out trial cohorts (n = 19, n = 30). STRING-db and multivariate analyses supplemented determinations of altered proteins via Wilcoxon matched pairs signed rank testing in XOI ULT responders. Mechanistic studies characterized proteomes of cultured XOI-treated murine bone marrow macrophages (BMDMs). At 48 weeks ULT, serum urate normalized in all gout patients, and flares declined in association with significantly altered proteins (p < 0.05) in clustering and proteome networks in sera and peripheral blood mononuclear cells. Sera demonstrated altered complement activation and regulatory gene ontology biologic processes. In both cohorts, a treatment-emergent serum interactome included key gouty inflammation mediators (C5, IL-1B, CXCL8, IL6). Last, febuxostat treatment decreased complement activation biologic process proteins in cultured BMDMs. Reduced gout flares are linked with a XOI treatment-emergent serum protein interactome that includes inflammation regulators, associated with altered complement activation and regulatory biologic processes. Serum and leukocyte proteomics could help identify when gouty inflammatory processes begin to subside in response to ULT. Trial Registration: ClinicalTrials.gov Identifier NCT02579096, posted October 19, 2015. [ABSTRACT FROM AUTHOR]

In patients with major depressive disorder, various functional areas are impaired, negatively impacting the quality of life. Remission can restore pre-depression functions; however, some patients may still have residual impairments. Distinguishing between near-normal recovery and residual impairment helps identify those at a high risk of relapse risk and helps tailor treatment. Accordingly, we aimed to discover and validate biomarkers that distinguish between near-normal recovery and residual impairment in remission states through serum proteome analysis. Pooled serum and individual serum samples from three groups (depression status, remission status with residual impairment, and remission status with normal recovery) were analyzed using liquid chromatography-tandem mass spectrometry. The combination of four proteins—antithrombin-III, serum amyloid A4 protein, C1q subcomponent subunit B, and serum amyloid P-component—was selected as a candidate biomarker. The trend of protein changes suggests complement C1q subcomponent subunit B and serum amyloid P-component as potential biomarkers for distinguishing remission from residual impairment. Changes in complement C1q subcomponent subunit B and serum amyloid P-component suggest that the complement system and inflammation-related immune mechanisms are associated with residual impairment in remittent major depressive disorder. [ABSTRACT FROM AUTHOR]

Infliximab (IFX) has transformed the management of inflammatory bowel diseases (IBD). While intravenous (IV) IFX has been effective, a subcutaneous (SC) formulation offers advantages in convenience and cost. However, there is lack of evidence regarding the transition from IV to SC-IFX, especially for patients with inadequate responses. This study investigates the effectiveness of switching from IV to SC-IFX in patients with inadequate responses during IV maintenance therapy. A retrospective study enrolled IBD patients who transitioned to SC-IFX after demonstrating inadequate responses during IV maintenance therapy. The study collected data of demographics of patients and dose and therapies administered prior to the IV-IFX. Primary outcomes included improvements in C-reactive protein (CRP) or fecal calprotectin (FC) levels. This study evaluated the trough levels and its differences between pre- and post-switching. Among 44 patients included, 10 exhibited CRP elevation before the switch, with 6 showing normalization post-switch. Similarly, 42 patients had elevated FC levels pre-switch, with 26 experiencing reductions post-switch. Trough levels increased after the switch. However, there were no significant differences between responders and non-responders. This study is the first study to investigate the transition therapy of IV to SC-IFX in patients with inadequate response. This suggests that SC-IFX could be a viable alternative in the management of IBD. However, further research is necessary to evaluate its efficacy in a larger population of patients who exhibit inadequate responses during IV-IFX maintenance therapy. [ABSTRACT FROM AUTHOR]

Background: Currently, the use of probiotics to treat inflammatory bowel diseases (IBD) is widely accepted because of their gut microbiota modulation capabilities and anti-inflammatory potential. Objective: The aim of this study is to examine the immunomodulatory outcomes of probiotics and sulfasalazine in the acetic acid-induced colitis murine model. Methods: The animals were randomly assigned to one of the seven groups. Following the induction of colitis, Lactobacillus acidophilus LA-5, Bifidobacterium animalis subsp. lactis BB-12, and sulfasalazine (SASP) were orally administered for 10 days. Subsequently, the in vitro anti-inflammatory effect on TNF-α and IL-10 in the supernatants of cultured spleen cells was assessed via ELISAs. Relative mRNA expression of ZO-1, MLCK, iNOS, TNFR2, ROR-γt, GATA-3, T-bet, and Foxp3 was determined using quantitative reverse‑transcription polymerase chain reaction (qRT‑PCR). Results: The SASP plus probiotic mixture was more effective in alleviating colitis symptoms, and reducing disease activity scores, and mucosal inflammation. qRT-PCR analysis revealed a significant reduction in T-bet and RORγt levels, while Foxp3 and GATA-3 levels increased in the colons of colitis mice. In addition, the selected strains substantially inhibited the release of inflammatory markers. Administration of LA-5 + BB-12 + SASP resulted in considerably higher inhibition of NO production and cell proliferation than in the other groups (p < 0.001). Treatment with LA-5 + BB-12 + SASP also reduced TNF-α-mediated apoptosis in intestinal epithelial cells (IECs). Conclusions: Survey results highlight that the combination regimen could be a promising strategy for IBD therapy, warranting further study of its clinical application and long-term benefits. [ABSTRACT FROM AUTHOR]

Intratumoral heterogeneity poses a significant challenge to the diagnosis and treatment of recurrent glioblastoma. This study addresses the need for non-invasive approaches to map heterogeneous landscape of histopathological alterations throughout the entire lesion for each patient. We developed BioNet, a biologically-informed neural network, to predict regional distributions of two primary tissue-specific gene modules: proliferating tumor (Pro) and reactive/inflammatory cells (Inf). BioNet significantly outperforms existing methods (p < 2e-26). In cross-validation, BioNet achieved AUCs of 0.80 (Pro) and 0.81 (Inf), with accuracies of 80% and 75%, respectively. In blind tests, BioNet achieved AUCs of 0.80 (Pro) and 0.76 (Inf), with accuracies of 81% and 74%. Competing methods had AUCs lower or around 0.6 and accuracies lower or around 70%. BioNet's voxel-level prediction maps reveal intratumoral heterogeneity, potentially improving biopsy targeting and treatment evaluation. This non-invasive approach facilitates regular monitoring and timely therapeutic adjustments, highlighting the role of ML in precision medicine. [ABSTRACT FROM AUTHOR]

Corticosteroids have always been recommended for severe cases of COVID-19. However, the efficacy of treatment with corticosteroids for COVID-19 during the SARS-CoV-2 omicron outbreak in China has not been reported. Clinical data from 406 patients hospitalized for severe/critical COVID-19 from December 2022 to January 2023 at six hospitals in Chongqing were retrospectively analyzed. The primary outcome was all-cause mortality at 28 days in the groups with and without corticosteroids treatment after propensity score matching (PSM). Secondary outcomes were to compare in-hospital mortality and length of survival time with corticosteroids and those without corticosteroids. This study included 406 patients with severe or critical COVID-19, divided into the corticosteroids group (231, 56.9%) and non-corticosteroids group (175, 43.1%). After PSM, the use of corticosteroids did not reduce all-cause mortality at 28 days (42.5% vs. 39.1%). Univariate analysis showed that corticosteroids were not associated with improved all-cause mortality at 28 days [hazard ratio (HR), 1.019; 95% confidence interval (CI), 0.639–1.623; p = 0.938]. Multivariate analysis showed similar results (HR, 1.047; 95% CI, 0.633–1.732; p = 0.858). Among non-survivors, the survival time was significantly larger in those who received corticosteroids compared with the non-corticosteroid users [median 13 (IQR 6.5–15.5) vs. 6 (4-11.25), p = 0.007]. The use of systemic corticosteroids in severe/critical COVID-19 may provide certain potential survival benefits but does not improve prognosis. [ABSTRACT FROM AUTHOR]

Migraine is a common and complex neurological disorder that has a high impact on quality of life. Recent advances with drugs that target the neuropeptide calcitonin gene-related peptide (CGRP) have helped, but treatment options remain insufficient. CGRP is released from trigeminal sensory fibers and contributes to peripheral sensitization, perhaps in part due to actions on immune cells in the trigeminovascular system. In this review, we will discuss the potential of cannabinoid targeting of immune cells as an innovative therapeutic target for migraine treatment. We will cover endogenous endocannabinoids, plant-derived phytocannabinoids and synthetically derived cannabinoids. The focus will be on six types of immune cells known to express multiple cannabinoid receptors: macrophages, monocytes, mast cells, dendritic cells, B cells, and T cells. These cells also contain receptors for CGRP and as such, cannabinoids might potentially modulate the efficacy of current CGRP-targeting drugs. Unfortunately, to date most studies on cannabinoids and immune cells have relied on cell cultures and only a single preclinical study has tested cannabinoid actions on immune cells in a migraine model. Encouragingly, in that study a synthetically created stable chiral analog of an endocannabinoid reduced meningeal mast cell degranulation. Likewise, clinical trials evaluating the safety and efficacy of cannabinoid-based therapies for migraine patients have been limited but are encouraging. Thus, the field is at its infancy and there are significant gaps in our understanding of the impact of cannabinoids on immune cells in migraine. Future research exploring the interactions between cannabinoids and immune cells could lead to more targeted and effective migraine treatments. [ABSTRACT FROM AUTHOR]

Our research explores the detrimental effects of microplastic (MP) exposure on adipose tissue aging and function, emphasizing the potential health risks associated with environmental pollutants. Utilizing both in vivo and in vitro models, we discovered that MPs accumulate in adipose tissues, leading to cellular senescence, inflammation, and hindered adipogenic differentiation. Notably, our findings demonstrate that MPs prompt an aging response in both epididymal and inguinal white adipose tissue, increase senescence-associated β-galactosidase activity, and upregulate key senescence and inflammatory markers. Furthermore, we show that MPs disrupt normal adipogenic differentiation by reducing lipid droplet formation and downregulating critical adipogenic markers. These insights highlight the urgent need for further investigation into the long-term consequences of MP pollution on biological aging and underscore the importance of developing public health strategies to mitigate these effects. [ABSTRACT FROM AUTHOR]

Background: Obesity is a risk factor for esophageal adenocarcinoma (EAC). It was reported that obesity -associated inflammation correlates with insulin resistance and increased risk of EAC. The objective of the study is to investigate the role of obesity associated inflammatory mediators in the development of EAC. Methods: We included 23 obese and nonobese patients with EAC or with or without Barrett's esophagus (BE) after IRB approval. We collected 23 normal, 10 BE, and 19 EAC tissue samples from endoscopy or esophagectomy. The samples were analyzed for the expression levels of pro-apoptotic and anti-apoptotic factors, PKC-δ, cIAP2, FLIP, IGF-1, Akt, NF-kB and Ki67 by immunofluorescence and RT-PCR. We compared the expression levels between normal, BE, and EAC tissue using Students' t-test between two groups. Results: Our results showed decreased gene and protein expression of pro-apoptotic factors (bad, bak and bax) and increased expression of anti-apoptotic factors (bcl-2, Bcl-xL) in BE and EAC compared to normal tissues. There was increased gene and protein expression of PKC-δ, cIAP2, FLIP, NF-kB, IGF-1, Akt, and Ki67 in BE and EAC samples compared to normal esophagus. Further, an increased folds changes in mRNA expression of proapoptotic factors, antiapoptotic factors, PKC-δ, IGF-1, Akt, and Ki-67 was associated with obesity. Conclusion: Patients with EAC had increased expression of cIAP2 and FLIP, and PKC-δ which is associated with inhibition of apoptosis and possible progression of esophageal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Recently, there has been increasing interest in the possible role of the gut microbiota (GM) in the onset of migraine. Our aim was to verify whether bacterial populations associated with intestinal dysbiosis are found in pediatric patients with migraine. We looked for which metabolic pathways, these bacteria were involved and whether they might be associated with gut inflammation and increased intestinal permeability. Methods: Patients aged between 6 and 17 years were recruited. The GM profiling was performed by the 16S rRNA metataxonomics of faecal samples from 98 patients with migraine and 98 healthy subjects. Alpha and beta diversity analyses and multivariate and univariate analyses were applied to compare the gut microbiota profiles between the two group. To predict functional metabolic pathways, we used phylogenetic analysis of communities. The level of indican in urine was analyzed to investigate the presence of metabolic dysbiosis. To assess gut inflammation, increased intestinal permeability and the mucosal immune activation, we measured the plasmatic levels of lipopolysaccharide, occludin and IgA, respectively. Results: The α-diversity analysis revealed a significant increase of bacterial richness in the migraine group. The β-diversity analysis showed significant differences between the two groups indicating gut dysbiosis in patients with migraine. Thirty-seven metabolic pathways were increased in the migraine group, which includes changes in tryptophan and phenylalanine metabolism. The presence of metabolic dysbiosis was confirmed by the increased level of indican in urine. Increased levels of plasmatic occludin and IgA indicated the presence of intestinal permeability and mucosal immune activation. The plasmatic LPS levels showed a low intestinal inflammation in patients with migraine. Conclusions: Pediatric patients with migraine present GM profiles different from healthy subjects, associated with metabolic pathways important in migraine. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin derived AL amyloidosis and transthyretin derived ATTR amyloidosis are the most common forms of cardiac amyloidosis. Both may present with cardiac arrhythmias, heart failure, and extracardiac symptoms. Disease outcome is often fatal. Recently, it was proposed that amyloid may cause cardiac inflammation. Here we tested the hypothesis that immune cell infiltration in cardiac tissue correlates with clinicopathological patient characteristics. Patients and methods: Myocardial biopsies from 157 patients with cardiac amyloidosis (46.5% AL, 53.3% ATTR) were immunohistochemically assessed for the presence and amount of T lymphocytes (CD3), macrophages (CD68) and neutrophils (MPO). Amyloid load, cardiomyocyte diameter, apoptosis (Caspase 3), necrosis (complement 9), and various clinical parameters were assessed and correlated with immune cell density. Results: Myocardial tissue was infiltrated with T lymphocytes (CD3), macrophages (CD68) and neutrophils (MPO) with variable amounts. Significant correlations were found between the number of macrophages and NYHA class. No correlations were found between the presence and amount of T lymphocytes, neutrophils and clinicopathological patient characteristics. Conclusion: The significant correlation between cardiac macrophage density and heart failure points towards a significant role of macrophages in disease pathology. [ABSTRACT FROM AUTHOR]

The most widely used cancer therapy is radiation therapy, but radiation damage to healthy tissues, particularly the gastrointestinal (GI) system, frequently reduces its effectiveness. This study investigates whether etoricoxib-loaded nanostructured lipid carriers (Et-NLC) could help shield the rat jejunum from radiation damage. Gamma irradiation (6 Gy) was used to damage the jejunum of Wistar albino rats, and then Et or Et-NLC (10 mg/kg b.w.) was administered orally for 14 days. It was found that the amounts of glutathione S-transferase (GST), superoxide dismutase (SOD), and nitric oxide (NO) decreased after irradiation but increased after Et-NLC therapy. Molecular analysis showed radiation-induced expression of microRNA-34a (miR34a), which may be involved in cellular stress response. Et-NLC treatments modulated the expression of miR34a, suggesting possible regulatory roles. Western blot analysis revealed changes in P53, interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-2 (COX-2) levels. Et-NLC treatments decreased TNF-α, IL-6, IL-10, and COX-2 levels, indicating anti-inflammatory actions. DNA fragmentation analysis revealed a decrease in apoptotic activity after Et-NLC treatments. A histopathological examination confirmed that Et-NLC treatments had attenuated radiation damage, which had improved vascularization and reduced inflammation. The findings show that Et-NLC is more effective than Et-alone at reducing damage to the jejunum caused by radiation by controlling inflammation, oxidative stress, and apoptotic activity. [ABSTRACT FROM AUTHOR]

Background: Numerous underlying causes can lead to inflammatory breast disorders. A wide range of non-specific symptoms may be presenting symptoms, which could cause a delay in diagnosis and thus improper therapy. Studies on artificial intelligence (AI) are rapidly developing and offer a wide range of possible uses in breast imaging. Artificial intelligence-based computer-assisted diagnosis (AI-CAD) holds promise in the field of mammography. It demonstrated diagnostic performances that are equivalent to or even better than those achieved by stand-alone methods. The current work aimed to identify whether AI can improve the performance of mammography in diagnosing inflammatory breast diseases and excluding the underlying malignancy in cases resistant to treatment that may reduce the need for interventional procedures such as biopsy. Methods: Our study was a retrograde one done on 34 patients with pathologically proven inflammatory breast lesions. Results: Suppurative breast lesions gave high false positive results. This was also the case with granulomatous mastitis; while simple inflammatory lesions gave true negative results on AI interrogation. Conclusions: Artificial intelligence can be of great value in diagnosing simple inflammatory breast lesions thus following up on such lesions can usually be sufficient without asking for unneeded biopsies. On the other hand, our study showed that AI had high false positive results in suppurative lesions and granulomatous mastitis. Consequently, ultrasonography can be more reliable in their diagnosis. [ABSTRACT FROM AUTHOR]

Background: Acetamiprid (ACE), a neonicotinoid insecticide, has been extensively used to control pests in agricultural and industrial environments. It has been reported that ACE is detrimental to the lungs. Nevertheless, the extent to which the activation of oxidative stress, inflammation, and cellular proliferation contributes to the pulmonary toxicity induced by ACE exposure remains insufficiently understood. This study explored the mechanism of toxicological consequences after ACE exposure in bronchial epithelial cells (BEAS-2B cells). The research also examined the potential ameliorative effects of the mixture of heat-killed Lactobacillus delbrueckii and Lactobacillus fermentum (HKL) on the toxicities of ACE. Results: Following 14 days of exposure to ACE at 0.5 and 1 μM, oxidative stress was induced, as evidenced by the decreased levels of reduced glutathione, catalase, glutathione peroxidase, and superoxide dismutase, along with increased levels of malondialdehyde. Also, ACE exposure results in overexpression and raised protein levels of the IL-25, NF-κB1, NF-κB2, IL-33, TSLP, and NF-κB target genes, which induce inflammatory responses. In addition, ACE boosted Ki-67-positive BEAS-2B cells. The molecular docking of ACE with target genes and their proteins demonstrated a potent binding affinity, further supported by the presence of hydrophobic contacts, electrostatic interactions, and hydrogen bonds. The post-treatment of HKL following the ACE (1 μM) exhibited its antioxidant, anti-inflammatory, and antiproliferative activities in suppressing ACE-induced toxicity. Conclusions: Our research revealed that ACE toxicity in BEAS-2B cells is caused by driving oxidative stress, pro-inflammatory response, and cellular proliferation. This study would give us a strategy to alleviate ACE-induced lung impairment by heat-killed probiotic supplements. As a result, dietary supplements that contain these microorganisms may potentially be beneficial in countries with high levels of pesticide contamination. [ABSTRACT FROM AUTHOR]

Research into the efficacy of photobiomodulation therapy (PBMT) in reducing inflammation has been ongoing for years, but standards for irradiation methodology still need to be developed. This study aimed to test whether PBMT stimulates in vitro human peripheral blood mononuclear cells (PBMCs) to synthesize pro-inflammatory cytokines, including chemokines. PBMCs were irradiated with laser radiation at two wavelengths simultaneously (λ = 808 nm in continuous emission and λ = 905 nm in pulsed emission). The laser radiation energy was dosed in one dose as a whole (5 J, 15 J, 20 J) or in a fractionated way (5 J + 15 J and 15 J + 5 J) with a frequency of 500, 1,500 and 2,000 Hz. The surface power densities were 177, 214 and 230 mW/cm2, respectively. A pro-inflammatory effect was observed at both the transcript and protein levels for IL-1β after PBMT at the energy doses 5 J and 20 J (ƒ=500 Hz) and only at the transcript level after application of PBMT at energy doses of 20 J (ƒ= 1,500; ƒ=2,000 Hz) and 5 + 15 J (ƒ=500 Hz). An increase in CCL2 and CCL3 mRNA expression was observed after PBMT at 5 + 15 J (ƒ=1,500 Hz) and 15 + 5 J (ƒ=2,000 Hz) and CCL3 concentration after application of an energy dose of 15 J (frequency of 500 Hz). Even though PBMT can induce mRNA synthesis and stimulate PBMCs to produce selected pro-inflammatory cytokines and chemokines, it is necessary to elucidate the impact of the simultaneous emission of two wavelengths on the inflammatory response mechanisms. [ABSTRACT FROM AUTHOR]

Lung ischemia-reperfusion injury (LIRI) causes oxidative stress, inflammation, and immune system activation. The Nrf2/Keap1/HO-1 pathway is important in cellular defense against these effects. Quercetin, a flavonoid with antioxidant, anti-inflammatory, and anti-cancer properties, has been investigated. Our aim in this study was to investigate the effect of quercetin on preventing lung ischemia-reperfusion injury and the role of the Nrf2/Keap1/HO-1 pathway. Sixty-four male Wistar rats were divided into four distinct groups(n = 16). Sham, lung ischemia-reperfusion (LIR), Saline + LIR, Quercetin + LIR (30 mg/kg i.p for a week before LIR). LIR groups were subjected to 60 min of ischemia (left pulmonary artery, vein, and bronchus) and 120 min of reperfusion. Our assessment encompassed a comprehensive analysis of various factors, including the evaluation of expression Nrf2, Keap1, and Heme Oxygenase-1 (HO-1) levels and NF-κB protein. Furthermore, we examined markers related to inflammation (interleukin-1β and tumor necrosis factor alpha), oxidative stress (malondialdehyde, total oxidant status, superoxide dismutase, glutathione peroxidase, total antioxidant capacity), lung edema (Wet/dry lung weight ratio and total protein concentration), apoptosis (Bax and Bcl2 protein), and histopathological alterations (intra-alveolar edema, alveolar hemorrhage, and neutrophil infiltration). Our results show that ischemia-reperfusion results in heightened inflammation, oxidative stress, apoptosis, lung edema, and histopathological damage. Quercetin showed preventive effects by reducing these markers, acting through modulation of the Nrf2/Keap1 pathway and inhibiting the NF-κB pathway. This anti-inflammatory effect, complementary to the antioxidant effects of quercetin, provides a multifaceted approach to cell protection that is important for developing therapeutic strategies against ischemia-reperfusion injury and could be helpful in preventive strategies against ischemia-reperfusion. [ABSTRACT FROM AUTHOR]

Background: The prevailing paradigm posits orthodontic tooth movement (OTM) as primarily a localized inflammatory process. In this study, we endeavor to elucidate the potential ramifications of mechanical force on systemic immunity, employing a time-dependent approach. Materials and methods: A previously described mouse orthodontic model was used. Ni-Ti. springs were set to move the upper 1st-molar in C57BL/6 mice and the amount of OTM was. measured by µCT. Mice were allocated randomly into four experimental groups, each. corresponding to clinical phases of OTM, relative to force application. Terminal blood. samples were collected and a comprehensive blood count test for 7 cell types as well as. proteome profiling of 111 pivotal cytokines and chemokines were conducted. Two controls. groups were included: one comprised non-treated mice and the other mice with inactivated springs. Results: Serum immuno-profiling unveiled alterations in cellular immunity, manifesting as. changes in percentages of leukocytes, monocytes, macrophages, neutrophils, and. lymphocytes, alongside key signaling factors in comparison to both control groups. The systemic cellular and molecular alterations triggered by OTM mirrored the dynamics previously described in the local immune response. Conclusions: Although the exact interplay between local and systemic immune responses to orthodontic forces require further elucidation, our findings demonstrate a tangible link between the two. Future investigations should aim to correlate these results with human subjects, and strive to delve deeper into the specific mechanisms by which mechanical force modulates the systemic immune response. [ABSTRACT FROM AUTHOR]

This work is an analytical review dedicated to the search for driver mechanisms of epigenetic changes in atherosclerosis pathogenesis. The disease affects the cardiovascular system in the adult population, mainly the elderly and senile. Atherosclerosis is accompanied by progressive deposition of cholesterol and lipoproteins in vessels intima with inflammation, narrowing of the lumen, and impaired blood supply to tissues and organs. These processes are characterized by changes in the expression of the CACNA1C, GABBR2, TCF7L2, DCK, NRP1, PBX1, FANCC, CCDC88C, TCF12, and ABLIM1 genes. Prevention of atherosclerosis is physical activity, the mechanisms of which are not fully understood. Experimental models have shown that regular training not only has a protective effect on the development of atherosclerosis but also inhibits the progression of an already developed disease with a decrease in vascular stenosis and an increase in the concentration of collagen and elastin and matrix metalloproteinases in plaques. These results have been confirmed by clinical studies. The purpose of this review was to systematize the accumulated results on the causes of epigenetic changes, including those under the influence of regular training, causing changes in the expression of specific microRNAs in atherosclerosis. It was found that physical exercise in Apo–/– mice increases the expression of miR-126 and miR-146a (inhibiting the TLR4 and TRAF genes), miR-20a (affecting PTEN), and miR-492 (suppressing RETN gene mRNA). Clinical studies have shown an increase in the levels of miR-146a, miR-126, miR-142-5p, and miR-424-5p and a decrease in the transcription of miR-15a-5p, miR-93-5p, and miR-451 under the influence of aerobic training. It has been suggested that the drivers of epigenetic changes in atherosclerosis are transposons pathologically activated during aging, the transcription of which can change under the influence of physical training, which is accompanied by impaired expression of long noncoding RNAs and microRNAs derived from transposons. Analysis of the published data allowed us to identify 36 such microRNAs, 25 of which showed identical changes in levels during aging and atherosclerosis. [ABSTRACT FROM AUTHOR]

Hepcidin production is regulated by iron concentration, erythropoietic activity, and inflammation. There is no reference method for determining its levels, but results obtained through various methods strongly correlate and can be compared using recalibration equations. Objective: To describe recalibrated serum hepcidin values at different percentiles in schoolchildren, considering age, sex, inflammatory processes, H. pylori infection, and iron status. Methods: Secondary analysis of data incorporating information on inflammation, H. pylori infection, and iron status of 349 schoolchildren. Hepcidin analysis was performed using a competitive ELISA, and recalibrated hepcidin values were calculated using the inverse of the linear regression model equation obtained by van der Vorm et al. Results: Recalibrated hepcidin values were lower than non-calibrated values. In schoolchildren without infection/inflammation and without iron deficiency, recalibrated values at the 50th percentile (25th–75th) were 4.89 ng/mL (2.68–8.42). For schoolchildren without infection/inflammation but with iron deficiency, recalibrated values were 2.34 ng/mL (1.10–6.58), the lowest hepcidin values observed. The highest values were found in the group with infection/inflammation, regardless of iron deficiency status. Conclusions: Recalibrated hepcidin values were lower than non-calibrated values. The highest values were observed in schoolchildren with infectious or inflammatory processes, and the lowest values were observed in schoolchildren with iron deficiency but only in the absence of infectious or inflammatory processes. Using recalibrated hepcidin values allows comparison between data obtained using different analytical methods. [ABSTRACT FROM AUTHOR]

Background: Renal ischemia-reperfusion injury (RIRI) is a critical phenomenon that compromises renal function and is the most serious health concern related to acute kidney injury (AKI). Pioglitazone (Pio) is a known agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ). PPAR-γ is a nuclear receptor that regulates genes involved in inflammation, metabolism, and cellular differentiation. Activation of PPAR-γ is associated with antiinflammatory and antioxidant effects, which are relevant to the pathophysiology of RIRI. This study aimed to investigate the protective effects of Pio in RIRI, focusing on oxidative stress and inflammation. Methods: We conducted a comprehensive literature search using electronic databases, including PubMed, ScienceDirect, Web of Science, Scopus, and Google Scholar. Results: The results of this study demonstrated that Pio has antioxidant, anti-inflammatory, and anti-apoptotic activities that counteract the consequences of RIRI. The study also discussed the underlying mechanisms, including the modulation of various pathways such as TNF-α, NF-κB signaling systems, STAT3 pathway, KIM-1 and NGAL pathways, AMPK phosphorylation, and autophagy flux. Additionally, the study presented a summary of various animal studies that support the potential protective effects of Pio in RIRI. Conclusion: Our findings suggest that Pio could protect the kidneys from RIRI by improving antioxidant capacity and decreasing inflammation. Therefore, these findings support the potential of Pio as a therapeutic strategy for preventing RIRI in different clinical conditions. Pioglitazone (Pio) plays a protective role in renal ischemia–reperfusion injury (RIRI) by regulating oxidative stress and inflammation responses. In an animal model of RIRI, Pio reduced inflammation, and oxidative stress renal tubule damage through several cellular pathways. It also promotes cell viability and inhibits autophagy. Pioe targets various pathways such as TNF-α, NF-κB signaling systems, KIM-1 and NGAL pathways, and AMPK phosphorylation. [ABSTRACT FROM AUTHOR]

Background and Aims: Upadacitinib is an oral selective Janus kinase (JAK) inhibitor approved in the United States for ulcerative colitis (UC) and Crohn's disease (CD). However, data regarding its use following prior treatment with the JAK inhibitor tofacitinib is sparse. As such, we aimed to evaluate the effectiveness of upadacitinib therapy following tofacitinib exposure. Methods: This is a multicenter retrospective study of patients with confirmed diagnosis of UC or CD who received upadacitinib after prior treatment with tofacitinib. The primary outcome of interest was patient-reported clinical improvement at first follow-up. Secondary outcome included discontinuation of corticosteroids, change in Mayo Endoscopic Score (MES) and change in inflammatory marker levels. Results: A total of 31 patients met the inclusion criteria. Following upadacitinib initiation, 80.6% (25/31) of patients had clinical improvement, including 92.3% (24/26) of those with UC and 20% (1/5) of those with CD. Of the patients initially requiring systemic corticosteroid therapy, 80% (12/15) were able to discontinue corticosteroids. Individual mean change of fecal calprotectin was a decrease of 501.5 mcg/g ± 608.6 (P value = 0.01) while C-reactive protein decreased on average by 14.8 mg/L ± 25.3 (P value = 0.02) compared to when patients were on tofacitinib, with significant changes observed in the UC cohort. In patients with UC, individual MES after initiating upadacitinib decreased compared to prior to tofacitinib discontinuation (P value = 0.04). Conclusion: Our study demonstrates that upadacitinib therapy in patients with prior tofacitinib exposure is associated with clinical improvement and a decrease in objective markers of inflammation in patients with UC. [ABSTRACT FROM AUTHOR]

Background: The Bacillus-derived cyclic lipopeptides (surfactin, iturin, and fengycin) form potent Heterogeneous Lipopeptide Micelle (HeLM) complexes. HeLM is a small molecule that has been shown to have immunomodulatory effects. However, how HeLM regulates inflammation is not clear, moreover its application to Inflammatory Bowel Disease (IBD), specifically Ulcerative Colitis (UC), has not been tested before. Aims: To use a murine model of IBD and determine the effects of HeLM and related molecular mechanisms of action. Methods: Colitis was induced in mice by administration of 4% Dextran Sodium Sulfate. Three preparations were tested against negative and positive controls: Purified HeLM, the wild-type strain that produces it, and an isogenic mutant that does not produce HeLM. Clinical, biochemical, and histological scoring systems were used to assess the severity of colitis. RT-qPCR and cell cultures were used to determine the levels of molecular signaling. Fecal samples were processed for metagenomic analysis. Results: Purified HeLM, and the wild-type strain, significantly decreased the severity of colitis as determined by the disease activity index (DAI), mouse colitis histology index (MCHI), fecal calprotectin, and colonic length. This effect was not seen in the mutant. HeLM was found to be an agonist to TLR-2, seemingly activating the Toll-Like Receptor 2/IL-10 pathway, with subsequent downregulation of inflammatory cytokines (TNF-α, IL-1β, and IL-6). At higher concentrations HeLM inhibited lipopolysaccharide ligands from activating TLR-4. The reduction in colitis was not due to microbiome modulation, as had previously been hypothesized. Conclusion: Our results indicate that HeLM ameliorates colitis by TLR-2-induced IL-10 production and possibly via the inhibition of lipopolysaccharide. [ABSTRACT FROM AUTHOR]

Background and Aims: Patients with inflammatory bowel disease (IBD) receiving infliximab (IFX) commonly experience immunogenic loss of response (LOR) by formation of anti-drug antibodies (ADAs). An immunomodulator (IMM) used in combination with initial IFX induction is known to reduce ADA development and improve clinical outcomes. We aimed to assess the impact of reactively adding an IMM to patients on IFX monotherapy. Methods: We conducted a retrospective cohort study and systematic review with meta-analysis of patients with IBD demonstrating immunologic LOR, with or without clinical LOR, that had an IMM (azathioprine, 6-mercaptopurine, or methotrexate) reactively added (reactive combination therapy; rCT) to combat elevated ADAs and raise IFX level. Data were extracted for pooled effect size estimation using random-effects models, and ADA and IFX trough levels were compared pre- and post-IMM initiation. Results: We identified 6 patients who received rCT due to rising ADA titers and low IFX levels. Median ADA titer decreased from 506 ng/mL (interquartile range (IQR) [416–750]) to 76.5 ng/mL (IQR [25.8–232]), an 85% decrease (p = 0.031). Median IFX trough increased from 0.4 µg/mL (IQR [0.4–0.48]) to 8.25 µg/mL (IQR [3.7–9.6]), a 20.6-fold increase (p = 0.038). Meta-analysis pooled effect size of 7 studies with 89 patients showed an 87% ADA titer reduction [95% confidence interval (CI) = 72–94%], 6.7-fold increased IFX trough (95% CI = 2.4–18.7), and 76% clinical remission rescue rate (95% CI = 59–93%). Conclusions: These results suggest rCT is a valid rescue strategy in patients with immunogenic LOR to IFX to reduce ADA titers, restore therapeutic IFX levels, and recapture clinical remission of IBD. [ABSTRACT FROM AUTHOR]

Purpose: One highlighted pathogenesis mechanism of diseases is the negative impact of pro-inflammatory diets (PD) on the gut microbiome. This systematic review aimed to study the link between dietary inflammatory index (DII), as an indicator of PD, and gut microbiome. Methods: A systematic search was done in PubMed and Scopus, adhering to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis. The assessment of the included studies' quality was performed using the critical appraisal checklist from the Joanna Briggs Institute. Results: Ten articles were included eight cross-sectional, one case-control, and, one cohort study. Seven and three included articles reported a weak and moderate relationship between gut microbiome and DII scores, respectively. DII scores were linked to variety in microbiome composition and diversity/richness. More importantly, anti-inflammatory diets as measured by lower DII scores were linked to a more desirable gut microbiome profile. Prevotella stercorea, Veillonella rogosae, Morganella morganii, Ruminococcus torques, Eubacterium nodatum, Alistipes intestine, Clostridium leptum, Morganellaceae family, Enterobacteriaceae family, and, Bacteroides thetaiotaomicron were related to higher DII scores. While, Butyrate-producing bacteria such as Ruminococcaceae and Lachnospiraceae families, Faecalibacterium prausnitzii, and Akkermansia muciniphila were related to lower DII scores. Conclusion: An anti-inflammatory diet, as measured by a lower DII score, might be linked to variations in the composition and variety of the microbiome. Therefore, the DII score could be useful in microbiota research, however, this possibility needs to be investigated more precisely in future studies. [ABSTRACT FROM AUTHOR]

Purpose: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic gastrointestinal disorders associated with significant morbidity and complications. This study investigates the therapeutic potential of docosahexaenoic acid (DHA) in a trinitrobenzene sulfonic acid (TNBS) induced colitis model, focusing on inflammation, oxidative stress, and intestinal membrane permeability. Methods: Wistar albino rats were divided into Control, Colitis, and Colitis + DHA groups (n = 8–10/group). The Colitis and Colitis + DHA groups received TNBS intrarectally, while the Control group received saline. DHA (600 mg/kg/day) or saline was administered via gavage for six weeks. Macroscopic and microscopic evaluations of colon tissues were conducted. Parameters including occludin and ZO-1 expressions, myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), Interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) levels were measured in colon tissues. Results: Colitis induction led to significantly higher macroscopic and microscopic damage scores, elevated TOS levels, reduced occludin and ZO-1 intensity, decreased mucosal thickness, and TAS levels compared to the Control group (p < 0.001). DHA administration significantly ameliorated these parameters (p < 0.001). MPO, MDA, TNF-α, and IL-6 levels were elevated in the Colitis group but significantly reduced in the DHA-treated group (p < 0.001 for MPO, MDA; p < 0.05 for TNF-α and IL-6). Conclusion: DHA demonstrated antioxidant and anti-inflammatory effects by reducing reactive oxygen species production, enhancing TAS capacity, preserving GSH content, decreasing proinflammatory cytokine levels, preventing neutrophil infiltration, reducing shedding in colon epithelium, and improving gland structure and mucosal membrane integrity. DHA also upregulated the expressions of occludin and ZO-1, critical for barrier function. Thus, DHA administration may offer a therapeutic strategy or supplement to mitigate colitis-induced adverse effects. [ABSTRACT FROM AUTHOR]

Purpose: Nut-enriched diets are related to improve lipid and inflammatory biomarkers in meta-analyses in the context of primary cardiovascular prevention. However, primary studies on secondary cardiovascular prevention are scarce and controversial. This systematic review and meta-analysis aimed to evaluate the effect of nut supplementation on lipid and inflammatory profiles in individuals with atherosclerotic cardiovascular disease, and the frequency of adverse events. Methods: Six databases were used for research: PubMed, EMBASE, BVS, Cochrane Library, Web of Science, and ClinicalTrials.gov, until February 2023, with no language restrictions. We performed random-effects meta-analyses to compare nut-enriched diets vs. control diets for pre-post intervention changes. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system assessed the evidence's certainty. Results: From the 5187 records identified, eight publications containing data referring to five randomized clinical trials involving 439 participants were included in the final analyses. The nuts evaluated were almonds, pecans, Brazil nuts, and mixed nuts, with doses ranging between 5 g and 85 g (median: 30 g/day). The intervention time varied between 6 and 12 weeks. Compared to nut-free diets, nut intake did not have a statistically significant effect on lipid profile biomarkers, except on the atherogenic index (MD: -0.32 [95% CI -0.58 to -0.06], I2 = 0% - moderate certainty of the evidence). Similarly, there was no effect of nuts on inflammatory profile biomarkers. It was not possible to aggregate data on adverse events. Conclusions: Nut supplementation did not change lipid and inflammatory profiles in the secondary cardiovascular prevention setting. [ABSTRACT FROM AUTHOR]

Purpose: Rheumatoid Arthritis (RA) has a point prevalence of around 20 million people worldwide. Patients with RA often believe that food intake affects disease activity, and that intake of red meat aggravate symptoms. The main objective of the Postprandial Inflammation in Rheumatoid Arthritis (PIRA) trial was to assess whether postprandial inflammation and serum lipid profile are affected differently by a meal including red meat, fatty fish, or a soy protein (vegan) meal. Methods: Using a randomized controlled crossover design, 25 patients were assigned to eat isocaloric hamburger meals consisting of red meat (60% beef, 40% pork), fatty fish (salmon), or soy protein for breakfast. Blood samples were taken before meals and at intervals up to 5 h postprandial. The analysis included the inflammation marker interleukin 6 (IL-6) and serum lipids. Results: No significant differences in postprandial IL-6 or triglyceride concentrations were found between meals. However, the area under the curve of very low density lipoprotein (VLDL) particle counts, as well as VLDL-4-bound cholesterol, triglycerides, and phospholipids, was higher after the fatty fish compared to both red meat and soy protein. Conclusion: Postprandial inflammation assessed by IL-6 did not indicate any acute negative effects of red meat intake compared to fatty fish- or soy protein in patients with RA. The fatty fish meal resulted in a higher number of VLDL-particles and more lipids in the form of small VLDL particles compared to the other protein sources. [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) is a chronic inflammatory condition that affects the gastrointestinal tract, particularly the ileum and colon. This disease is characterized by recurrent bouts of intestinal inflammation with subsequent bowel wall damage, including scarring (i.e., fibrosis) and abnormal smooth muscle proliferation. MR enterography, an MRI examination tailored to assess the small bowel, is a first-line diagnostic tool for diagnosing CD in children, characterization and monitoring of disease severity and extent, and assessment of disease-related complications. To date, such MRI evaluations have been mostly qualitative, which can adversely impact diagnostic performance and inter-radiologist agreement. Quantitative MRI methods have been shown to aid in the evaluation of a variety of medical conditions and have been increasingly investigated in children and adults with CD. In CD, such objective techniques have been used to assist with diagnosis, assess treatment response, and characterize bowel wall histologic abnormalities. In the current work, we will review quantitative MRI methods for detecting and measuring intestinal active inflammation (MRI-based scoring systems, T1 relaxation mapping, diffusion-weighted imaging, intra-voxel incoherent motion, mesenteric phase contrast), bowel wall damage (magnetization transfer), and motility (quantitative cine imaging) in small bowel CD, with an emphasis on the pediatric population. [ABSTRACT FROM AUTHOR]

Purpose: Incisional hernia is a common postoperative complication; however, few transcriptomic studies have been conducted on it. In this study, we used second-generation high-throughput sequencing to explore the pathogenesis and potential therapeutic targets of incisional hernias. Methods: Superficial fasciae were collected from 15 patients without hernia and 21 patients with an incisional hernia. High-throughput sequencing of the fascia was performed to generate an expression matrix. We analyzed the matrix to identify differentially expressed genes (DEGs) and performed gene ontology and enrichment analyses of these DEGs. Additionally, an external dataset was utilized to identify key DEGs. Results: We identified 1,823 DEGs closely associated with extracellular matrix (ECM) imbalance, bacterial inflammatory response, and fibrillar collagen trimerization. TNNT3, CMAY5, ATP1B4, ASB5, CILP, SIX4, FBN1 and FNDC5 were identified as key DEGs at the intersection of the two expression matrices. Moreover, non-alcoholic fatty liver disease-related, TNF, and IL-17 signaling pathways were identified as key enrichment pathways. Conclusions: We identified eight key DEGs and three pathways associated with incisional hernias. Our findings offer new insights into the pathogenesis of incisional hernias and highlight potential targets for their prevention and treatment. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that N6-methyladenosine (mA) modification of RNA affects fundamental aspects of RNA metabolism, and mA dysregulation is implicated in various human diseases, including Alzheimer's disease (AD). This study is designed to explore the role and mechanism of methyltransferase-like 14 (METTL14) in the pathogenesis of AD. SK-N-SH cells were treated with Aβ1–42 to establish an in vitro model of AD. Cerebellin 4 (CBLN4) and METTL14 expression levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability and apoptosis were analyzed using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry assay. B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), C-caspase-3, total-caspase-3, C/EBP homologous protein (CHOP), and glucose-related protein 78 (GRP78) protein levels were determined using Western blot. Interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) levels were analyzed using ELISA. Reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) products were examined using special assay kits. Interaction between CBLN4 and METTL14 was verified using methylated RNA immunoprecipitation (MeRIP) and dual-luciferase reporter assays. CBLN4 and METTL14 expression was decreased in Aβ1-42-treated SK-N-SH cells. Upregulation of CBLN4 relieved Aβ1-42-induced SK-N-SH cell apoptosis, inflammation, oxidative stress, and endoplasmic reticulum (ER) stress in vitro. At the molecular level, METTL14 could improve the stability and expression of CBLN4 mRNA via m6A methylation. Our findings indicated that m6A methylase METTL14-mediated upregulation of CBLN4 mRNA stability could repress Aβ1-42-triggered SK-N-SH cell injury, providing a promising therapeutic target for AD treatment. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) as a neurodegenerative dementia is reviewed based on its mechanisms of development, the impact of genetic factors on its aetiology, and epigenetic interaction. The hypotheses proposed on AD mechanisms examined briefly include amyloid-β, protein cascade, tau-protein, cholinergic neurone, vascular, inflammation cascade, and calcium hypotheses. This review provides insight into the potential of antioxidant intervention in the management of AD in retrospect of the pathophysiology. The database search engines PubMed, Scopus, ScienceDirect, and Google Scholar were searched in writing this article; using the keywords pathophysiology, Alzheimer's disease, natural antioxidants, camel milk, and taurine, emphasis is laid on the oxidative stress mechanism underlying AD development and the role of oxidative biomarkers. The promising interventions by antioxidants and their beneficial effects on AD amelioration are highlighted. Natural antioxidants with potential beneficial effects in the management of AD include taurine and active constituents of medicinal plants and food, such as flavonoids, non-flavonoids, and mitochondrial-targeted antioxidants. Others are organo-sulphate compounds, carotenoids, and camel milk. The natural antioxidants exhibit neuroprotective activities by neutralising reactive oxygen species (ROS) and protecting the brain cells from ROS-induced damage. They inhibit the aggregation of amyloid-β and ameliorate inflammatory responses, leading to a reduction in AD-associated neurodegeneration. In conclusion, prophylactic and therapeutic interventions, involving anti-amyloid and/or anti-inflammatory agents, as well as co-administration of antioxidants as an adjunctive therapy, based on consideration of individual variations in oxidative stress levels and genetic factors, may yield substantial benefits. Such interventions may enhance the efficacy of treatment outcomes in AD. [ABSTRACT FROM AUTHOR]

Pulmonary inflammation is a condition that can result from different diseases such as asthma, chronic obstructive pulmonary disease, and influenza as well as other antigenic substances including a high-fat diet. The potency of syringic acid (SYR), a bioactive substance with therapeutic properties, was evaluated on high-fat (HF) diet–induced pulmonary inflammation in male Wistar rats. Thirty male rats were randomly grouped into five: control, SYR (50 mg/kg), HF only, HF + SYR (25 mg/kg), and HF + SYR (50 mg/kg). Animals were sacrificed after 7 weeks of SYR treatments. Blood, bronchoalveolar lavage fluid (BALF), and lungs were collected for biochemical and histopathological analyses. SYR at 50 mg/kg significantly reversed the HFD-induced dyslipidemia. Furthermore, the observed alterations in both the enzymic and non-enzymic oxidative indicators (MDA, SOD, CAT, and GST) due to intake of HF were ameliorated by SYR. A further dose-dependent increase in GSH was observed following treatments. The increased levels of inflammatory cytokines (NF-κB, IL6, TNF-α, and COX-2) quantified in the BALF and lung tissue were significantly lowered when treated with SYR. Furthermore, exposure to HF lowered the inflammatory indices (albumin) quantified in the BALF, while the levels of LDH and globulin were significantly increased. Also, inflammatory indices including platelet/lymphocytes and (neutrophils × platelets)/lymphocytes quantified in the BALF were significantly lowered with SYR treatments, while over twofold increase in albumin/globulin ratio was recorded by 50 mg/kg SYR. SYR demonstrated antioxidative and anti-inflammatory effects via inhibition of HF-induced activation of pro-inflammatory cytokines in rats. Summary of the findings in this study [ABSTRACT FROM AUTHOR]

Several recent studies have shown that hypoxia preconditioning, often mimicked by sub-toxic levels of cobalt, can protect body tissues against various types of inflammatory and oxidative injuries. The present study was designed to understand the effects of low-to-moderate doses of cobalt chloride (CoCl2) on ulcerative colitis induced by acetic acid in male Wistar rats. Rats were pre-treated with CoCl2 at 10, 30 and 60 mg/kg BW for 7 days prior to, and later along with intra-rectal administration of 4% acetic acid for another 3 days. Rats were euthanized and the colons were examined macroscopically, and histologically, haematological parameters were evaluated in the blood and various oxidative stress parameters and inflammatory cytokines were studied in the colon and blood. Pre-treatment with CoCl2 at 10 mg/kg caused reduction in colonic levels of hydrogen peroxide (H2O2), nitric oxide (NO), advanced oxidation protein products (AOPP) and reduced serum TNF-α, but increased serum IL-10 levels. Conversely, rats treated with higher doses of CoCl2 showed exacerbation of macroscopic scores and histologic damage in the colon, with significantly elevated levels of oxidants and serum TNF-α along with reduced serum IL-10 levels. Values of all the measured haematological parameters (PCV, Hb, RBC, WBC and platelet count) were dose-dependently increased with increasing doses of CoCl2. The results of this study showed that consumption of cobalt at low doses could play a vital role in the control of ulcerative colitis, while higher doses can contribute to exacerbation of intestinal inflammation. Monitoring of cobalt concentrations in food and water consumed by ulcerative colitis patients is imperative to prevent exacerbation of colonic inflammation by cobalt. [ABSTRACT FROM AUTHOR]

Objective: Adenoid hypertrophy is a prevalent pediatric condition, often necessitating surgical intervention. Intranasal steroid administration shows promise as a conservative treatment, particularly by inducing apoptosis in adenoidal cells, leading to a reduction in adenoid size and inflammation. This study aims to characterize the expression profile of caspase-3 as an apoptotic inducer protein in inflammatory and epithelial adenoid tissues and explore its association with steroid administration. Methods: We performed immunohistochemical staining for caspase-3 proteins in adenoid tissues obtained from 51 pediatric patients aged between 2.5 and 12 years (mean age: 6.09 ± 2.1 years) who underwent adenoid surgery. A retrospective analysis of clinical data was conducted, categorizing participants into steroid treatment receivers (n = 25) and non-receivers (n = 26). Subsequently, the lymphoid inflammatory tissue and epithelial tissue from the adenoid were compared in terms of caspase-3 protein expression, and associated clinical variables were assessed. Results: Immunohistochemical analysis revealed significant caspase-3 expression in inflammatory tissues. The expression levels were scored, and no significant correlation was observed between inflammation and epithelium based on caspase-3 expression (correlation coefficient = 0.143; p > 0.05). Furthermore, demographic and clinical characteristics did not show a statistically significant difference in caspase-3 expression levels. Conclusion: Caspase-3 expression was significant in inflammatory adenoid tissue, but it showed no association with nasal steroid administration. [ABSTRACT FROM AUTHOR]

Objective and design: The aim of this study was to investigate the effects of ethanol exposure on epigenetic markers in bone marrow (BM) and their impact on inflammatory response during Aspergillus fumigatus infection. Results: Chronic ethanol exposure decreased H3K27me3 enrichment in the Il6 promoter region while increased H3K4me3 enrichment in Tnf. Chimeric mice were generated by transplanting BM from mice exposed to ethanol or water. Infection of ethanol-chimeric mice culminated in higher clinical scores, although there was no effect on mortality. However, previous chronic exposure to ethanol affects persistently the inflammatory response in lung tissue, demonstrated by increased lung damage, neutrophil accumulation and IL-6, TNF and CXCL2 production in ethanol-chimeric mice, resulting in a decreased neutrophil infiltration into the alveolar space. Neutrophil killing and phagocytosis were also significantly lower. Moreover, BM derived macrophages (BMDM) from ethanol-chimeric mice stimulated with A. fumigatus conidia exhibited higher levels of TNF, CXCL2 and IL-6 release and a higher killing activity. The Il6 promoter of BMDM from ethanol-chimeric mice exhibited a reduction in H3K27me3 enrichment, a finding also observed in BM donors exposed to ethanol. Conclusions: These evidences demonstrate that prior chronic alcohol exposure of bone-marrow modify immune effector cells functions impairing the inflammatory response during A. fumigatus infection. These findings highlight the persistent impact of chronic ethanol exposure on infectious disease outcomes. [ABSTRACT FROM AUTHOR]

Background: Inflammation, a biological response of the immune system, can be triggered by various factors such as pathogens, damaged cells, and toxic compounds. These factors can lead to chronic inflammatory responses, potentially causing tissue damage or disease. Both infectious and non-infectious agents, as well as cell damage, activate inflammatory cells and trigger common inflammatory signalling pathways, including NF-κB, MAPK, and JAK-STAT pathways. These pathways are activated through adaptor proteins, which possess distinct protein binding domains that connect corresponding interacting molecules to facilitate downstream signalling. Adaptor molecules have gained widespread attention in recent years due to their key role in chronic inflammatory diseases. Methods: In this review, we explore potential pharmacological agents that can be used to target adaptor molecules in chronic inflammatory responses. A comprehensive analysis of published studies was performed to obtain information on pharmacological agents. Conclusion: This review highlights the therapeutic strategies involving small molecule inhibitors, antisense oligonucleotide therapy, and traditional medicinal compounds that have been found to inhibit the inflammatory response and pro-inflammatory cytokine production. These strategies primarily block the protein-protein interactions in the inflammatory signaling cascade. Nevertheless, extensive preclinical studies and risk assessment methodologies are necessary to ensure their safety. [ABSTRACT FROM AUTHOR]

Background: Transient receptor potential vanilloid type 4 (TRPV4) is a versatile ion channel with diverse roles in immune cells, including macrophages. While its function in inflammation remains debated, we investigated its role in regulating IL-10 production and its impact on macrophage reprogramming during inflammation. Methods: We investigated the connection between TRPV4 activation and CREB-mediated IL-10 production during inflammation. Notably, this signaling pathway was found to reprogram macrophages and enhance their ability to resist inflammatory damage. The experiments were conducted on primary macrophages and were further corroborated by animal studies. Results: In response to TRPV4 activation during inflammation, we observed a significant increase in intracellular Ca2+ levels, which triggered the activation of the transcription factor CREB, subsequently upregulating IL-10 production. This IL-10 played a pivotal role in reprogramming macrophages to withstand inflammatory damage. Using a mouse model of acute lung injury (ALI), we confirmed that TRPV4 activation during ALI led to IL-10 secretion, but this increase did not significantly contribute to inflammation resolution. Moreover, we found that TRPV4 prevented the accumulation of dysfunctional mitochondria in macrophages through the CREB-IL-10 axis during inflammation. Suppression of CREB or TRPV4 inhibition exacerbated mitochondrial dysfunction, while treatment with recombinant IL-10 mitigated these effects. Additionally, IL-10 induced mitophagy and cleared dysfunctional mitochondria in LPS-exposed cells. Conclusion: Our study highlights the essential role of TRPV4 in regulating IL-10 production and mitochondrial health in macrophages during inflammation. These findings contribute to understand the role of TRPV4 in immune responses and suggest potential therapeutic targets for modulating inflammation-induced cellular dysfunction. [ABSTRACT FROM AUTHOR]

Susceptibility to decompression sickness (DCS) is characterized by a wide inter-individual variability, the origins of which are still poorly understood. We selectively bred rats with at least a 3-fold greater resistance to DCS than standard rats after 6 generations. In order to better understand DCS mechanisms, we compared the static genome expression of these resistant rats from the 10th generation to their counterparts of the initial non-resistant Wistar strain, by a microarray transcriptomic approach coupled and crossed with a PCR plates miRnome study. Thus, we identified differentially expressed genes on selected males and females, as well as gender differences in those genes, and we crossed these transcripts with the respective targets of the differentially expressed microRNAs. Our results highlight pathways involved in inflammatory responses, circadian clock, cell signaling and motricity, phagocytosis or apoptosis, and they confirm the importance of inflammation in DCS pathophysiology. Static hepatic gene expression of resistant rats crossed with their circulating miRnome highlight the role of inflammatory pathways in the susceptibility and pathophysiology of decompression sickness. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening condition triggered by the body's extreme response to an infection, leading to widespread inflammation, organ dysfunction, and potentially fatal complications. While lupeol, a significant phytosterol found in various herbal plants, has been considered as a potential anti-cancer agent, its anti-septic activities and underlying molecular mechanisms remain unclear. The aim of this study is to investigate the effects of lupeol on a cecal ligation and puncture (CLP)-induced septic mouse model. Animals were categorized into six groups: control, CLP-operated, CLP plus maslinic acid, and CLP plus lupeol (0.5, 1, or 2 mg/kg). The assessment included survival rate, body weight changes, inflammatory cytokines, and histological analyses. Additionally, human endothelial cells were stimulated with high mobility group box1 (HMGB1) protein and lupeol, with cell viability determined. Inflammatory markers and gene expression were evaluated through enzymelinked immunosorbent assay and Western blot analysis, respectively. After CLP surgery, the group treated with lupeol showed improved survival rates and body weight compared to the untreated control group. Lupeol treatment also decreased levels of tumor necrosis factor (TNF)-α, interleukin-1β, nitric oxide, and cytokines associated with kidney inflammation. When administered to HMGB1-activated cells, lupeol reduced the expression of Toll-like receptor 4 and TNF-α, while simultaneously activating phosphoinositide 3-kinase/AKT signaling to enhance cell survival. In conclusion, lupeol demonstrated anti-inflammatory properties and conferred protective effects against CLP-induced sepsis, reinforcing cell survival in the face of septic responses. [ABSTRACT FROM AUTHOR]

Purpose: We explore the use of intravenously delivered fluorescent perfluorocarbon (PFC) nanoemulsion tracers and multi-spectral cryo-fluorescence tomography (CFT) for whole-body tracer imaging in murine inflammation models. CFT is an emerging technique that provides high-resolution, three-dimensional mapping of probe localization in intact animals and tissue samples, enabling unbiased validation of probe biodistribution and minimizes reliance on laborious histological methods employing discrete tissue panels, where disseminated populations of PFC-labeled cells may be overlooked. This methodology can be used to streamline the development of new generations of non-invasive, cellular-molecular imaging probes for in vivo imaging. Procedures: Mixtures of nanoemulsions with different fluorescent emission wavelengths were administered intravenously to naïve mice and models of acute inflammation, colitis, and solid tumor. Mice were euthanized 24 h post-injection, frozen en bloc, and imaged at high resolution (~ 50 µm voxels) using CFT at multiple wavelengths. Results: PFC nanoemulsions were visualized using CFT within tissues of the reticuloendothelial system and inflammatory lesions, consistent with immune cell (macrophage) labeling, as previously reported in in vivo magnetic resonance and nuclear imaging studies. The CFT signals show pronounced differences among fluorescence wavelengths and tissues, presumably due to autofluorescence, differential fluorescence quenching, and scattering of incident and emitted light. Conclusions: CFT is an effective and complementary methodology to in vivo imaging for validating PFC nanoemulsion biodistribution at high spatial localization, bridging the resolution gap between in vivo imaging and histology. [ABSTRACT FROM AUTHOR]

Purpose: Myocardial infarction (MI) with subsequent inflammation is one of the most common heart conditions leading to progressive tissue damage. A reliable imaging marker to assess tissue viability after MI would help determine the risks and benefits of any intervention. In this study, we investigate whether a new mitochondria-targeted imaging agent, 18F-labeled 2'-deoxy-2'-18F-fluoro-9-β-d-arabinofuranosylguanine ([18F]F-AraG), a positron emission tomography (PET) agent developed for imaging activated T cells, is suitable for cardiac imaging and to test the myocardial viability after MI. Procedure: To test whether the myocardial [18F]-F-AraG signal is coming from cardiomyocytes or immune infiltrates, we compared cardiac signal in wild-type (WT) mice with that of T cell deficient Rag1 knockout (Rag1 KO) mice. We assessed the effect of dietary nucleotides on myocardial [18F]F-AraG uptake in normal heart by comparing [18F]F-AraG signals between mice fed with purified diet and those fed with purified diet supplemented with nucleotides. The myocardial viability was investigated in rodent model by imaging rat with [18F]F-AraG and 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) before and after MI. All PET signals were quantified in terms of the percent injected dose per cc (%ID/cc). We also explored [18F]FDG signal variability and potential T cell infiltration into fibrotic area in the affected myocardium with H&E analysis. Results: The difference in %ID/cc for Rag1 KO and WT mice was not significant (p = ns) indicating that the [18F]F-AraG signal in the myocardium was primarily coming from cardiomyocytes. No difference in myocardial uptake was observed between [18F]F-AraG signals in mice fed with purified diet and with purified diet supplemented with nucleotides (p = ns). The [18F]FDG signals showed wider variability at different time points. Noticeable [18F]F-AraG signals were observed in the affected MI regions. There were T cells in the fibrotic area in the H&E analysis, but they did not constitute the predominant infiltrates. Conclusions: Our preliminary preclinical data show that [18F]F-AraG accumulates in cardiomyocytes indicating that it may be suitable for cardiac imaging and to evaluate the myocardial viability after MI. [ABSTRACT FROM AUTHOR]