Features Of Inflammation Research Articles

Eicosanoid profiles in an arthritis model: Effects of a soluble epoxide hydrolase inhibitor

Rheumatoid arthritis is a common systemic inflammatory autoimmune disease characterized by damage to joints, inflammation and pain. It is driven by an increase of inflammatory cytokines and lipids mediators such as prostaglandins. Epoxides of polyunsaturated fatty acids (PUFAs) are lipid chemical mediators in a group of regulatory compounds termed eicosanoids. These epoxy fatty acids (EpFA) have resolutive functions but are rapidly metabolized by the soluble epoxide hydrolase enzyme (sEH) into the corresponding diols. The pharmacological inhibition of sEH stabilizes EpFA from hydrolysis, improving their half-lives and biological effects. These anti-inflammatory EpFA, are analgesic in neuropathic and inflammatory pain conditions. Nonetheless, inhibition of sEH on arthritis and the resulting effects on eicosanoids profiles are little explored despite the physiological importance. In this study, we investigated the effect of sEH inhibition on collagen-induced arthritis (CIA) and its impact on the plasma eicosanoid profile. We measured the eicosanoid metabolites by LC–MS/MS-based lipidomic analysis. The treatment with a sEH inhibitor significantly modulated 11 out of 69 eicosanoids, including increased epoxides 12(13)-EpODE, 12(13)-EpOME, 13-oxo-ODE, 15-HEPE, 20-COOH-LTB4 and decreases several diols 15,6-DiHODE, 12,13-DiHOME, 14,15-DiHETrE, 5,6-DiHETrE and 16,17-DiHDPE. Overall the inhibition of sEH in the rheumatoid arthritis model enhanced epoxides generally considered anti-inflammatory or resolutive mediators and decreased several diols with inflammatory features. These findings support the hypothesis that inhibiting the sEH increases systemic EpFA levels, advancing the understanding of the impact of these lipid mediators as therapeutical targets.

Sulforaphane alleviates oxidative stress induced by oxidized fish oil in Litopenaeus vannamei by involving antioxidant capacity, inflammation, autophagy, and apoptosis

Sulforaphane (SFN) is an antioxidant. Unsaturated fatty acids are rich in fish oil, and they are indispensable fatty acids for aquatic animals to grow and reproduce. However, fish oil is easily oxidized, which could have adverse effects on aquatic animals. In this study, Litopenaeus vannamei was divided into four groups: fresh fish oil group (control group), oxidized fish oil group (OFO group), OFO plus low-concentration SFN group (OFO + SL group), and OFO plus high-concentration SFN group (OFO + SH group). A 28-day experiment was conducted, and the antioxidant capacity, inflammation, autophagy, and pathological characteristics were investigated to explore whether SFN could protect L. vannamei from oxidative stress induced by OFO. Results showed that OFO significantly increased the contents of MDA in hepatopancreas, muscle and serum, while high concentrations of SFN significantly decreased the MDA compared with the OFO group (P < 0.05). OFO significantly affected the expression of SOD, CAT, GST and HSP 70 and increased the expression of inflammatory-related genes (TNF and spz). SFN downregulated the expression of TNF and spz, upregulate Nrf2, heat shock protein 70 (HSP 70) and autophagy genes (ATG4, ATG5, ATG10, and ATG12) and stabilized the expression of apoptosis-related genes (caspase 2, caspase 3, and JNK, P < 0.05). In addition, histological analysis of hepatopancreas showed that OFO led to cavitation in the lumen, and the existence of SFN reversed this phenomenon. OFO also result in the apoptosis of the hepatopancreas of L. vannamei, and the existence of high-concentration SFN reduced its apoptosis. In summary, SFN is involved in the regulation of antioxidant capacity, inflammation, autophagy, and apoptosis to alleviate the oxidative stress induced by OFO in L. vannamei.

Inflammatory and Metabolic Signaling Interfaces of the Hypertrophic and Senescent Chondrocyte Phenotypes Associated with Osteoarthritis.

Osteoarthritis (OA) is a complex disease of whole joints with progressive cartilage matrix degradation and chondrocyte transformation. The inflammatory features of OA are reflected in increased synovial levels of IL-1β, IL-6 and VEGF, higher levels of TLR-4 binding plasma proteins and increased expression of IL-15, IL-18, IL-10 and Cox2, in cartilage. Chondrocytes in OA undergo hypertrophic and senescent transition; in these states, the expression of Sox-9, Acan and Col2a1 is suppressed, whereas the expression of RunX2, HIF-2α and MMP-13 is significantly increased. NF-kB, which triggers many pro-inflammatory cytokines, works with BMP, Wnt and HIF-2α to link hypertrophy and inflammation. Altered carbohydrate metabolism and the upregulation of GLUT-1 contribute to the formation of end-glycation products that trigger inflammation via the RAGE pathway. In addition, a glycolytic shift, increased rates of oxidative phosphorylation and mitochondrial dysfunction generate reactive oxygen species with deleterious effects. An important surveyor mechanism, the YAP/TAZ signaling system, controls chondrocyte differentiation, inhibits ageing by protecting the nuclear envelope and suppressing NF-kB, MMP-13 and aggrecanases. The inflammatory microenvironment and synthesis of key matrix components are also controlled by SIRT1 and mTORc. Senescent chondrocytes represent the functional end stage of hypertrophic differentiation and characteristically upregulate p16 and p21, but also a variety of inflammatory cytokines, chemokines and metalloproteinases, developing the senescence-associated secretory phenotype. Senolysis with dendrobin, miR29b-5p and other agents has been shown to be efficient under experimental conditions, and appears to be a promising tool for the treatment of OA, as it restores COL2A1 and aggrecan synthesis, suppressing NF-kB and destructive metalloproteinases.

Intestinal permeability and inflammatory features of juvenile age correlate with the eventual systemic autoimmunity in lupus-prone female SWR × NZB F1 (SNF1) mice.

The incidence of systemic lupus erythematosus (SLE) is about nine times higher in women than in men, and the underlying mechanisms that contribute to this gender bias are not fully understood. Previously, using lupus-prone (SWR × NZB)F1 (SNF1) mice, we have shown that the intestinal immune system could play a role in the initiation and progression of disease in SLE, and depletion of gut microbiota produces more pronounced disease protection in females than in males. Here, we show that the gut permeability features of lupus-prone female SNF1 mice at juvenile ages directly correlate with the expression levels of pro-inflammatory factors, faecal IgA abundance and nAg reactivity and the eventual systemic autoantibody levels and proteinuria onset. Furthermore, we observed that the disease protection achieved in female SNF1 mice upon depletion of gut microbiota correlates with the diminished gut inflammatory protein levels, intestinal permeability and circulating microbial DNA levels. However, faecal microbiota transplant from juvenile male and females did not result in modulation of gut inflammatory features or permeability. Overall, these observations suggest that the early onset of intestinal inflammation, systemic autoantibody production and clinical stage disease in lupus-prone females is linked to higher gut permeability in them starting at as early as juvenile age. While the higher gut permeability in juvenile lupus-prone females is dependent on the presence of gut microbes, it appears to be independent of the composition of gut microbiota.

Associations of serum cortisol and inflammatory marker features with depression and anxiety in young women with gynecologic cancer.

Serum cortisol and inflammatory markers may play a role in depression and anxiety, but little is known about whether various features of serum cortisol and inflammatory markers have different associations with depression and anxiety. This study examines the associations of serum cortisol and inflammatory marker features with depression and anxiety in young women with gynecologic cancer. Sixty-four young women with gynecologic cancer, aged 15-39 years, were recruited in a tertiary general hospital and a tertiary hospital specializing in oncology in China from May to December 2021. The Hospital Anxiety and Depression Scale was used to evaluate depression and anxiety. Blood samples were taken at 8 am, 4 pm, and 10 pm on the same day to examine the various features (average, variability, and diurnal patterns) of serum cortisol and inflammatory markers, namely C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). Young women with gynecologic cancer who reported depression/anxiety had significantly higher average levels of serum cortisol, IL-6 and TNF-α than those who did not. The dysregulations in the diurnal patterns of serum cortisol and IL-6 were associated with depression and anxiety. Serum cortisol levels were significantly higher in the depression/anxiety group at 10 pm. Depression and anxiety were associated with elevated levels of IL-6 and TNF-α at each time point. This study revealed various associations of serum cortisol and inflammatory marker features with depression and anxiety in young women with gynecologic cancer. Further research is needed to understand the role of serum cortisol and inflammatory marker features in the progression of depression and anxiety.

COVID myocarditis: a review of the literature.

Myocarditis is a potentially fatal complication of coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. COVID-19 myocarditis appears to have distinct inflammatory characteristics that distinguish it from other viral etiologies. COVID-19 myocarditis can present with symptoms ranging from dyspnea and chest pain to acute heart failure and death. It is critical to detect any cases of myocarditis, especially fulminant myocarditis, which can be characterized by signs of heart failure and arrhythmias. Serial troponins, echocardiography, and electrocardiograms should be performed as part of the initial workup for suspected myocarditis. The second step in detecting myocarditis is cardiac magnetic resonance imaging and endomyocardial biopsy. Treatment for COVID-19 myocarditis is still debatable; however, combining intravenous immunoglobulins and corticosteroids may be effective, especially in cases of fulminant myocarditis. Overall, more research is needed to determine the incidence of COVID-19 myocarditis , and the use of intravenous immunoglobulins and corticosteroids in combination requires large randomized controlled trials to determine efficacy. The purpose of this review is to summarize current evidence on the subject. This review aims to summarise current evidence on this topic.

The impact of saccharolytic and proteolytic fermentation products in the pathogenesis of metabolic associated diseases. Review

The article highlights the research data on the role of saccharolytic and proteolytic fermentation products in the pathogenetic mechanisms of the development of metabolically associated diseases. A brief description of the composition, number and function of the normal intestinal microbiome is given. Data on the peculiarities of saccharolytic and proteolytic fermentation in the intestines are given. The role of the gut microbiota in the formation of such metabolically associated diseases as obesity, type 2 diabetes mellitus and non‑alcoholic fatty liver disease has also been described. The influence of short‑chain fatty acids, namely propionate, succinate and butyrate, in regulating the metabolism and secretion of insulin, leptin, as well as satiety hormones, namely glucagon‑like peptide 1 and peptide YY, is given in detail. The effects of proteolytic fermentation products on the metabolism and functioning of the intestine‑liver axis, as well as on the processes of carbohydrate metabolism, are carefully described. Descriptions of the effects of protein fermentation products of intestinal microbiota on intestinal pro‑inflammatory reactions and the progression of non‑alcoholic fatty liver disease are provided. The combined data, obtained from rodent and human investigations, regarding effects of short‑chain fatty acids on adipose tissue metabolism. In particular, the ability of acetate to inhibit intracellular lipolysis in adipocytes has been proven. The effects of essential short‑chain fatty acids on intestinal permeability are also described. The most important role of short‑chain fatty acids in the development of inflammatory processes, in particular low‑grade inflammation characteristic of metabolically associated diseases, is emphasized. The data have been presented from investigations of the role of acetate, butyrate and propionate in non‑alcoholic fatty liver disease and type 2 diabetes mellitus.

Hemato-biochemical and inflammatory features in canine pyometra

Hemato-biochemical and inflammatory features in canine pyometra

Hepcidin as a key regulator of iron homeostasis triggers inflammatory features in the normal endometrium

Menstrual blood, containing high iron levels, can undergo retrograde transport into the abdominal cavity. Excess iron causes oxidative stress and inflammation. Iron metabolism is regulated by hepcidin, and serum hepcidin levels are increased in patients with endometriosis; however, the functions of hepcidin in normal endometrium remain unclear. We therefore aimed to examine hepcidin concentrations in patients with endometriosis and to determine if iron accumulation and hepcidin increased the production of reactive oxygen species (ROS) and inflammation in normal endometrial cells. We determined hepcidin levels in peritoneal fluid and menstrual blood from patients with and without endometriosis (25/16 and 15/15 patients, respectively). We also examined the effects of hepcidin on ferroportin expression, iron accumulation, and ROS generation in normal endometrial stromal cells (NESCs) from 20 women who underwent surgery for uterine leiomyoma, using immunohistochemistry and immunofluorescence analyses and analyzed its effect on the expression of inflammatory cytokines by real-time polymerase chain reaction. There was no significant difference in iron concentrations in menstrual blood or peritoneal fluid between women with and without endometriosis; however, women with endometriosis had significantly higher hepcidin levels in menstrual blood. Hepcidin reduced the expression of ferroportin in NESCs and promoted the accumulation of ferrous iron. Hepcidin plus ferrous iron increased the production of ROS and inflammatory cytokines compared with ferrous iron alone. These results indicate that women with endometriosis have high hepcidin levels in menstrual blood, leading to increased iron production, oxidative stress, and inflammation, which may, in turn, promote the development of endometriosis.

Macrophage-derived inflammation promotes pulmonary vascular remodeling in hypoxia-induced pulmonary arterial hypertension mice

The role of inflammation in pulmonary hypertension is gradually gaining increasing research attention. However, no previous study has evaluated the characteristics of inflammation during chronic hypoxia-induced pulmonary hypertension. Therefore, the aim of this study was to investigate the characteristics of the inflammatory process involved in hypoxia-induced pulmonary hypertension in mice. The current study evaluated from day 4 to day 28 of hypoxia, the PAAT and PAAT/PET decreased, accompanied by pulmonary vascular remodeling and right ventricular hypertrophy, as well as increased numbers of CD68 macrophages. The expression of the pro-inflammatory factors IL-1β and IL-33 increased, but decreased on day 28. The expression of IL-12 increased from day 4 to day 28, whereas that of the anti-inflammatory factor IL-10 in lung tissue decreased. Furthermore, the expression of the IL-33/ST2 signaling pathway also increased over time under hypoxic conditions. In conclusion, pulmonary artery remodeling in HPH mice worsens progressively in a time-dependent manner, with inflammatory cell infiltration predominating in the early stage and pulmonary vascular remodeling occurring in the later stage.

CETP Expression in Bone-Marrow-Derived Cells Reduces the Inflammatory Features of Atherosclerosis in Hypercholesterolemic Mice.

CETP activity reduces plasma HDL-cholesterol concentrations, a correlate of an increased risk of atherosclerotic events. However, our recent findings suggest that CETP expression in macrophages promotes an intracellular antioxidant state, reduces free cholesterol accumulation and phagocytosis, and attenuates pro-inflammatory gene expression. To determine whether CETP expression in macrophages affects atherosclerosis development, we transplanted bone marrow from transgenic mice expressing simian CETP or non-expressing littermates into hypercholesterolemic LDL-receptor-deficient mice. The CETP expression did not change the lipid-stained lesion areas but decreased the macrophage content (CD68), neutrophil accumulation (LY6G), and TNF-α aorta content of young male transplanted mice and decreased LY6G, TNF-α, iNOS, and nitrotyrosine (3-NT) in aged female transplanted mice. These findings suggest that CETP expression in bone-marrow-derived cells reduces the inflammatory features of atherosclerosis. These novel mechanistic observations may help to explain the failure of CETP inhibitors in reducing atherosclerotic events in humans.

Th1/17 polarization and potential treatment by an anti-interferon-γ DNA aptamer in Hunner-type interstitial cystitis

Hunner-type interstitial cystitis (HIC) is a rare, enigmatic inflammatory disease of the urinary bladder with no curative treatments. In this study, we aimed to characterize the unique cellular and immunological factors specifically involved in HIC by comparing with cystitis induced by Mycobacterium bovis bacillus Calmette-Guérin, which presents similar clinicopathological features to HIC. Here, we show that T helper 1/17+polarized immune responses accompanied by prominent overexpression of interferon (IFN)-γ, enhanced cGAS-STING cytosolic DNA sensing pathway, and increased plasma cell infiltration are the characteristic inflammatory features in HIC bladder. Further, we developed a mouse anti-IFN-γ DNA aptamer and observed that the intravesical instillation of the aptamer significantly ameliorated bladder inflammation, pelvic pain and voiding dysfunction in a recently developed murine HIC model with little migration into the blood. Our study provides the plausible basis for the clinical translation of the anti-IFN-γ DNA aptamer in the treatment of human HIC.

Potential subtype-specific therapeutic approaches in small cell lung cancer.

Small cell lung cancer (SCLC) remains one of the most aggressive thoracic malignancies with an especially dismal prognosis. While the detection of various targetable driver mutations and immune checkpoints have revolutionized the treatment of non-small cell lung cancer (NSCLC), there has been only modest therapeutic innovation over the past decades in SCLC. In this review, we aim to provide a brief summary on the clinical relevance of recent research findings, which could soon pave the way towards a more personalized and targeted management of SCLC patients. Substantial research on the biological and molecular heterogeneity of SCLC has been conducted in the last years. Recent results from comprehensive profiling studies have shown that unique major SCLC subtypes can be distinguished based on the relative expression of key transcription regulators (ASCL1, NEUROD1, POU2F3) or distinct inflammatory features. Understanding the differing molecular characteristics of these distinct subtypes has resulted in the identification of specific therapeutic vulnerabilities. The recently introduced molecular SCLC subtype classification represents a substantial progress towards a personalized and more efficacious approach in SCLC. The consequences of this paradigm shift provide hope for improved patient care and clinical outcomes in this exceptionally lethal thoracic malignancy.

Prevalence, risk indicators, and clinical characteristics of peri-implant mucositis and peri-implantitis for an internal conical connection implant system: A multicenter cross-sectional study.

Peri-implant disease prevalence is associated with a multifactorial etiology and distinct clinical characteristics of inflammation. The present study aimed to assess the prevalence of peri-implant diseases, identify related risk indicators, and associate specific clinical characteristics to peri-implant biological complications in the medium term. Peri-implant diseases were classified according to established case criteria. Patients' data, implant and/or prosthetic features, and maintenance records were collected. Clinical characteristics such as bleeding on probing (BOP), suppuration (SUPP), keratinized mucosa (KM), probing depth (PD), marginal recession (MR), and modified plaque index (mPI) were recorded. Ninety-nine patients with 266 implants with a mean functional duration of 30.26 months were evaluated. Peri-implant mucositis and peri-implantitis prevalence totaled to 49.5% and 15.15% (patient level), respectively. Peri-implant mucositis was associated with osteoporosis (odds ratio [OR] 6.09), age (OR 0.97), diabetes mellitus (OR 3.09), cemented-retained prosthesis (OR 3.81), and partial prosthesis (OR 2.21). Peri-implantitis was associated with osteoporosis (OR 7.74) and periodontitis (OR 2.74), cemented prosthesis (OR 10.12), partial and full arch prostheses (OR 12.35 and 19.86), implant diameter (OR 3.64), abutment transmucosal height (OR 3.39), and hygiene difficulty (OR 3.14). Furthermore, mPI score 3 (OR 3.27) and PD scores (OR 1.64) were associated with peri-implant mucositis, while mPI score 3 (OR 16.42), KM (OR 1.53), PD (OR 1.81), MR (OR 2.61), and the relationship between KM and PD (OR 0.63) were associated with peri-implantitis. In the medium term, peri-implant diseases were correlated with factors inherent to the patient's conditions, presurgical treatment plan, and hygiene maintenance care. The knowledge of the mentioned factors and featured clinical characteristics can be crucial for disease prevention and establishment of a superior implant therapy prognosis.

Novel frameshift variants expand the map of the genetic defects in IRF2BP2.

At present, the knowledge about disease-causing mutations in IRF2BP2 is very limited because only a few patients affected by this condition have been reported. As previous studies have described, the haploinsufficiency of this interferon transcriptional corepressors leads to the development of CVID. Very recently, a more accurate phenotype produced by truncating variants in this gene has been defined, manifesting CVID with gastrointestinal inflammatory symptoms and autoimmune manifestations. We analyzed 5 index cases with suspected primary immunodeficiency by high throughput sequencing. They were submitted for a genetic test with a panel of genes associated with immune system diseases, including IRF2BP2. The screening of SNVs, indels and CNVs fulfilling the criteria with very low allelic frequency and high protein impact, revealed five novel variants in IRF2BP2. In addition, we isolated both wild-type and mutated allele of the cDNA from one of the families. In this study, we report five novel loss-of-function (LoF) mutations in IRF2BP2 that likely cause primary immunodeficiency, with CVID as more frequent phenotype, variable expression of inflammatory gastrointestinal features, and one patient with predisposition of viral infection. All identified variants were frameshift changes, and one of them was a large deletion located on chromosome 1q42, which includes the whole sequence of IRF2BP2, among other genes. Both de novo and dominant modes of inheritance were observed in the families here presented, as well as incomplete penetrance. We describe novel variants in a delimited low-complex region, which may be considered a hotspot in IRF2BP2. Moreover, this is the first time that a large CNV in IRF2BP2 has been reported to cause CVID. The distinct mechanisms than LoF in IRF2BP2 could cause different phenotype compared with the mainly described. Further investigations are necessary to comprehend the regulatory mechanisms of IRF2BP2, which could be under variable expression of the disease.

Comprehensive Grading System of Inflammatory Features of the Lumbar Facet Joints on Magnetic Resonance Imaging.

Retrospective. We aimed to describe a magnetic resonance imaging (MRI)-based grading system of inflammatory features of the lumbar facet joints using an atlas and assess its reliability. Chronic low back pain is often caused by facet joint arthropathy. Inflammatory features are often evident on MRI. While several grading systems of facet arthropathy have been described, there is scant data on the reliability of these systems, and none focus exclusively on inflammatory features. We describe a grading system that assesses facet joint effusion, bone marrow edema, and soft tissue edema. Each feature was graded from 0 to 3 (facet edema) or 0 to 2 (bone marrow edema intensity and extent, soft tissue edema intensity and extent). Four spine experts graded MRIs of 50 subjects at the bilateral L3/4, L4/5, and L5/S1 levels. All subjects had symptomatic facet arthropathy and received therapeutic facet joint injections. We assessed the intra-reader and inter-reader reliability of each feature at each joint and summarized across all six joints. The mean age of subjects was 56 years (SD = 17), and 48% were female. The injections occurred at the L3/4 level in 12% of cases, at L4/5 in 88%, and at L5/S1 in 80% of cases. The intra-reader reliability kappa's for each feature ranged from 0.42 to 0.81. In contrast, the inter-reader reliability kappa values for each feature ranged from 0.37 to 0.54. MRI inflammatory features of the lumbar facet joints are often noted in patients with low back pain. The proposed grading system is reliable and could serve as a research tool for studies assessing the clinical relevance and prognostic value of these features.

Asthmatics only sensitized to Staphylococcus aureus enterotoxins have more exacerbations, airflow limitation, and higher levels of sputum IL-5 and IgE.

Staphylococcus aureus Enterotoxins (SE) may act as superantigens and induce an intense T cell activation causing local production of polyclonal IgE and resultant eosinophil activation. To assess whether asthma with sensitization to SE but not to common aero-allergens (AA) displays different inflammatory characteristics. We conducted a prospective study on a series of 110 consecutive patients with asthma recruited from the University Asthma Clinic of Liege. We compared clinical, functional and inflammatory characteristics of this general population of asthmatics categorized in 4 groups according to sensitization to AA and/or SE. We also compared sputum supernatant cytokines in patients sensitized to SE or not. Asthmatics only sensitized to AA represented 30%, while 29% were sensitized to both AA and SE. One fifth of the population had no specific IgE. Sensitization to SE but not to AA (21%) was associated with later onset of disease, higher rate of exacerbations, nasal polyps and more severe airway obstruction. As for airway type-2 biomarkers, patients presenting with specific IgE against SE (SE-IgE) displayed higher FeNO, sputum IgE and sputum IL-5 levels but not IL-4. We confirm that the presence of SE-IgE is associated with elevated serum IgE to levels well above those observed in patients only sensitized to AA. Our study suggests that asthma specialists should measure SE-IgE during the phenotyping process as it may allow the identification of a subgroup of patients with more asthma exacerbations, more nasal polyposis and chronic sinusitis, lower lung function and more intense type-2 inflammation.

A novel clinical-radscore nomogram for predicting ruptured intracranial aneurysm

ObjectivesOur study aims to find the more practical and powerful method to predict intracranial aneurysm (IA) rupture through verification of predictive power of different models. MethodsClinical and imaging data of 576 patients with IAs including 192 ruptured IAs and matched 384 unruptured IAs was retrospectively analyzed. Radiomics features derived from computed tomography angiography (CTA) images were selected by t-test and Elastic-Net regression. A radiomics score (radscore) was developed based on the optimal radiomics features. Inflammatory markers were selected by multivariate regression. And then 4 models including the radscore, inflammatory, clinical and clinical-radscore models (C–R model) were built. The receiver operating characteristic curve (ROC) was performed to evaluate the performance of each model, PHASES and ELAPSS. The nomogram visualizing the C–R model was constructed to predict the risk of IA rupture. ResultsFive inflammatory features, 2 radiological characteristics and 7 radiomics features were significantly associated with IA rupture. The areas under ROCs of the radscore, inflammatory, clinical and C–R models were 0.814, 0.935, 0.970 and 0.975 in the training cohort and 0.805, 0.927, 0.952 and 0.962 in the validation cohort, respectively. ConclusionThe inflammatory model performs particularly well in predicting the risk of IA rupture, and its predictive power is further improved by combining with radiological and radiomics features and the C–R model performs the best. The C–R nomogram is a more stable and effective tool than PHASES and ELAPSS for individually predicting the risk of rupture for patients with IA.

Enrichment of Activated Fibroblasts as a Potential Biomarker for a Non-Durable Response to Anti-Tumor Necrosis Factor Therapy in Patients with Crohn's Disease.

We investigated whether the response to anti-tumor necrosis factor (anti-TNF) treatment varied according to inflammatory tissue characteristics in Crohn's disease (CD). Bulk RNA sequencing (RNA-seq) data were obtained from inflamed and non-inflamed tissues from 170 patients with CD. The samples were clustered based on gene expression profiles using principal coordinate analysis (PCA). Cellular heterogeneity was inferred using CiberSortx, with bulk RNA-seq data. The PCA results displayed two clusters of CD-inflamed samples: one close to (Inflamed_1) and the other far away (Inflamed_2) from the non-inflamed samples. Inflamed_1 was rich in anti-TNF durable responders (DRs), and Inflamed_2 was enriched in non-durable responders (NDRs). The CiberSortx results showed that the cell fraction of activated fibroblasts was six times higher in Inflamed_2 than in Inflamed_1. Validation with public gene expression datasets (GSE16879) revealed that the activated fibroblasts were enriched in NDRs over Next, we used DRs by 1.9 times pre-treatment and 7.5 times after treatment. Fibroblast activation protein (FAP) was overexpressed in the Inflamed_2 and was also overexpressed in the NDRs in both the RISK and GSE16879 datasets. The activation of fibroblasts may play a role in resistance to anti-TNF therapy. Characterizing fibroblasts in inflamed tissues at diagnosis may help to identify patients who are likely to respond to anti-TNF therapy.

Integration of scRNA-Seq and bulk RNA-Seq uncover perturbed immune cell types and pathways of Kawasaki disease.

Kawasaki disease (KD) is an acute febrile illness primarily affecting children and characterized by systemic inflammation and vasculitis that can lead to coronary artery complications. The aim of this study was to gain a comprehensive understanding of immune dysregulation in KD. To this end, we employed integration of single-cell RNA sequencing (scRNA-Seq) and bulk RNA sequencing (bulk RNA-Seq) data. Furthermore, we conducted flow cytometry analysis for a cohort of 82 KD patients. Our analysis revealed significant heterogeneity within immune cell populations in KD patients, with distinct clusters of T cells, B cells, and natural killer (NK) cells. Importantly, CD4+ naïve T cells in KD patients were found to predominantly differentiate into Treg cells and Th2 cells, potentially playing a role in the excessive inflammation and vascular damage characteristic of the disease. Dysregulated signaling pathways were also identified, including the mTOR signaling pathway, cardiomyopathy pathway, COVID-19 signaling pathway, and pathways involved in bacterial or viral infection. These findings provide insights into the immunopathogenesis of KD, emphasizing the importance of immune cell dysregulation and dysregulated signaling pathways. Integration of scRNA-Seq and bulk RNA-Seq data offers a comprehensive view of the molecular and cellular alterations in KD and highlights potential therapeutic targets for further investigation. Validation and functional studies are warranted to elucidate the roles of the identified immune cell types and pathways in KD pathogenesis and to develop targeted interventions to improve patient outcomes.