Search Results (41)

Systemic sclerosis (SSc) is an autoimmune disease marked by fibrosis in various organs, including the heart. Cardiac involvement influences prognosis, but the underpinning mechanisms remain unclear. This study investigates myocardial changes in a murine SSc model induced by subcutaneous injection of HOCl, with a specific focus on alterations in structural proteins and inflammatory markers, oxidative stress, and vascular remodeling. Hearts were collected from SSc mice after 6 weeks, and structural, inflammatory, and oxidative stress markers were evaluated by Hematoxylin and Eosin (H&E) staining, Masson’s Trichrome, and immunohistochemical analysis. Increased vimentin and α-SMA expression were detected in the vasculature, indicating endothelial dysfunction and myofibroblast activation, alongside a decrease in CD31 expression, consistent with an endothelial-to-mesenchymal transition (EndMT). Concomitant increases in macrophage (CD68, F4/80, EP29, EPR1) and inflammasome markers (Caspase-1, IL-1β and NLPR-3) were observed together with a remarkably augmented level of MMP3, MMP9, Collagen I and TGF-β, thus suggesting that inflammation and matrix remodeling correlate with endothelial dysfunction. Accordingly, the increased levels of NRF2 and HOMX1 suggested a compensatory protective response against oxidative stress. These data suggest that both immune cell- and inflammasome-mediated inflammation signaling play a key role in endothelial dysfunction by altering the balance between fibrosis and vascular remodeling markers. Full article

This study investigated the effects of potassium magnesium sulfate (PMS) on intestinal dissociation and absorption rate, immune function, and expression of the NOD-like receptor thermal domain-associated protein 3 (NLRP3) inflammasome, aquaporins (AQPs), and potassium and magnesium ion channels in weaned piglets. Experiment 1 involved the assessment of the dissociation rate of PMS in pig digestive fluid and the absorption rate of PMS in the small intestine using an Ussing chamber in vitro. In Experiment 2, 216 healthy 21-day-old weaned piglets were selected and randomly assigned to six groups (0%, 0.15%, 0.30%, 0.45%, 0.60%, and 0.75% PMS), with each group 6 replicates of six piglets per replicate. The in vitro Ussing chamber results indicated that the absorption of K⁺ and Mg²⁺ in the jejunum and ileum was significantly higher than that in the duodenum (p < 0.05). The in vivo study demonstrated that the addition of PMS resulted in a linear increase in serum K⁺, IgG, and interleukin (IL)-2 levels while simultaneously reducing serum IL-1β levels (p < 0.05). Dietary PMS significantly elevated serum IL-10 and Mg²⁺ levels in feces (p < 0.05). Furthermore, supplementation with 0.60% or 0.75% PMS significantly downregulated the mRNA expression of NLRP3 in the jejunum (p < 0.05). Dietary PMS supplementation linearly reduced the mRNA expression levels of cysteine protease 1 (Caspase-1) and IL-1β in both the jejunum and colon as well as the mRNA expression levels of two-pore domain channel subfamily K member 5 (KCNK5) in these regions (p < 0.05). Notably, supplementation with 0.15% PMS significantly decreased the mRNA expression of transient receptor potential channel 6 (TRPM6) in the jejunum and significantly increased the expression of TRPM6 in the colon (p < 0.05). Dietary addition of 0.45% and 0.60% PMS significantly increased the mRNA expression of aquaporin 3 (AQP3) in the colon (p < 0.05), whereas 0.75% PMS significantly increased the mRNA expression of aquaporin 8 (AQP8) in both the jejunum and colon. Moreover, the expression levels of AQP3 and AQP8 were significantly negatively correlated with the diarrhea rate observed between days 29 and 42. In conclusion, dietary PMS supplementation improved immune function, inhibited the activation of intestinal NLRP3, and modulated the expression of water and ion channels in weaned piglets, thereby contributing to the maintenance of intestinal water and ion homeostasis, which could potentially alleviate post-weaning diarrhea in piglets. The recommended supplemental level of PMS in the corn-soybean basal diet for weaned piglets is 0.30%. Full article

This study investigated the protective effects of Garcinia biflavonoid 1 (GB1) against dextran sulfate sodium (DSS)-induced ulcerative colitis and its underlying mechanisms. Using wild-type (WT) and NLRP3 knockout (Nlrp3^-/-) mice, we demonstrated that GB1 administration significantly ameliorated colitis symptoms, as evidenced by improved body weight, disease activity index (DAI) scores, colon length, and histological damage in WT mice. Mechanistically, GB1 downregulated pro-inflammatory mediators (IL-6, NF-κB, and CD11b) while attenuating the expression of NLRP3 inflammasome components (ASC, Caspase-1, and IL-1β). Notably, these protective effects were abolished in Nlrp3^-/- mice, confirming the essential role of NLRP3 in GB1-mediated mitigation of colitis. Furthermore, GB1 reinforced intestinal barrier integrity by preserving tight junctions, reducing permeability, and attenuating mucosal inflammation. Collectively, our findings highlight GB1 as a promising therapeutic candidate for colitis treatment, primarily through NLRP3 inflammasome suppression and intestinal barrier restoration. Full article

Background: Acute pulmonary embolism (PE) is a condition with increased morbidity and mortality. It is important to identify patients with high mortality risk. Inflammation and thrombosis are interconnected in the pathophysiology of PE. The aim of the study was to investigate the prognostic value of multiple blood cellular indices such as neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte platelet ratio (NLPR), systemic immune–inflammation index (SII), systemic inflammation response index (SIRI) and aggregate index of systemic inflammation (AISI) in acute PE. Methods: A total of 157 patients with acute PE confirmed by chest computed tomographic angiography (CTPA) were enrolled. These patients were divided into two categories according to the simplified pulmonary embolism severity index (sPESI): high risk and low risk. Results: Univariate logistic regression analysis showed that right ventricle dysfunction, NLR, SII and SIRI were significantly associated with high risk of acute PE. NLR of 4.32 was associated with high-risk PE with a sensitivity of 57.4% and specificity of 65.7% (AUC = 0.635). SII of 1086.55 was associated with high-risk PE with a sensitivity of 55.7% and specificity of 71.4% (AUC = 0.614). SIRI of 2.87 was associated with high-risk PE with a sensitivity of 59% and specificity of 62.9% (AUC = 0.624). Multivariate logistic regression analysis demonstrated that right ventricle dysfunction, NLR, PLR and NLPR are independent predictors of high-risk acute PE. Secondly, NLR, NLPR, SII and SIRI were significantly correlated with in-hospital mortality of acute PE. Based on receiver-operating characteristic (ROC) curve values of 7.66 for NLR (AUC 0.911, sensitivity of 85.7% and sensibility of 83%), 0.02 for NLPR (AUC 0.871, sensitivity of 85.7% and sensibility of 70%), 1542.71 for SII (AUC 0.782, sensitivity of 71.4% and sensibility of 72%) and 5.72 for SIRI (AUC 0.788, sensitivity of 71.4% and sensibility of 73%) could predict in-hospital mortality. Conclusions: The blood cellular indices (NLR, NLPR, SII and SIRI) are associated with high-risk acute PE and in-hospital mortality. Right ventricular dysfunction, NLR and NLPR are independent predictors for high-risk acute PE. Full article

Rheumatoid arthritis (RA) is an autoimmune disorder that leads to severe cartilage deterioration and synovial impairment in the joints. Previous studies have indicated that the aberrant activation of the NLRP3 inflammasome in synovial macrophages plays a significant role in the pathogenesis of RA and has been regarded as a therapeutic target for the disease. In this study, we synthesized a novel canthin-6-one alkaloid, namely methyl canthin-6-one-2-carboxylate (Cant), and assessed its effects on NLRP3 inflammasome activation in macrophages. Our data reveal that exposure to Cant significantly suppressed the transcription and secretion of multiple pro-inflammatory mediators, including IL-1β, IL-6, IL-18, TNF-α, NO, and COX2, in a dose-dependent manner. These alterations were associated with changes in the activation of various signaling pathways, including NF-kB, MAPK, and PI3K-AKT pathways. Notably, pretreatment with Cant significantly reduced LPS/ATP-induced activation of the NLRP3 inflammasome, as evidenced by the decline in the cleaved forms of IL-1β and caspase-1 in cell culture supernatants of BMDMs. Regarding the mechanisms, our data show that Cant could enhance the expression of Nrf2 in macrophages, which play an inhibitory role in ROS production. Collectively, our data demonstrate that Cant might suppress the activation of the NLRP3 inflammasome by upregulating the production of Nrf2, suggesting that Cant could serve as a candidate for the further development of anti-RA drugs. Full article

Polycystic ovarian syndrome (PCOS) is a multifaceted metabolic and hormonal disorder in females of reproductive age, frequently associated with cardiac disturbances. This research aimed to explore the protective potential of adropin and/or tirzepatide (Tirze) on cardiometabolic aberrations in the letrozole-induced PCOS model. Female Wistar non-pregnant rats were allotted into five groups: CON; PCOS; PCOS + adropin; PCOS + Tirze; and PCOS + adropin+ Tirze. The serum sex hormones, glucose, and lipid profiles were securitized. Cardiac phosphorylated levels of AKT(pAKT), glycogen synthase kinase-3 beta (pGSK-3β), NOD-like receptor family pyrin domain containing 3 (NLPR3), IL-1β and IL-18 were assayed. The cardiac redox status and endoplasmic reticulum stress (ER) parameters including relative glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) gene expressions were detected. Finally, the immunoreactivity of cardiac NF-κB, Bcl2, and BAX were assessed. Our results displayed that adropin and/or Tirze intervention successfully alleviated the PCOS-provoked cardiometabolic derangements with better results recorded for the combination treatment. The synergistic effect of adropin and Tirze is mostly mediated via activating the cardiac Akt, which dampens the GSK3β/NF-κB/NLRP3 signaling pathway, with a sequel of alleviating oxidative damage, inflammatory response, ER stress, and related apoptosis, making them alluring desirable therapeutic targets in PCOS-associated cardiac complications. Full article

Background: Blunt thoracic trauma possesses unique physiopathological traits due to the complex interaction of immune and coagulation systems in the lung tissue. Hemogram-based ratios such as neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), neutrophil-to-lymphocyte × platelet (NLPR) ratios have been studied as proxies for immune dysregulation and survival in trauma. We hypothesized that blunt thoracic trauma patients exhibit distinct patterns of coagulation and inflammation abnormalities identifiable by the use of readily available hemogram-derived markers. Methods: The present study represents a retrospective observational analysis that included 86 patients with blunt thoracic trauma from a single high-volume level one trauma center. The primary outcome was mortality prediction in blunt thoracic trauma patients using these derived biomarkers. Secondary outcomes included phenotypes of the immune response and coagulopathy and the prediction of non-fatal adverse events. Results: A U-shaped distribution of mortality was found, with high rates of early deaths in patients with an NLPR value of <3.1 and high rates of late deaths in patients with NLPR > 9.5. A subgroup of blunt thoracic trauma patients expressing moderate inflammation and inflammation-induced hypercoagulation objectified as NLPR between 3.1 and 9.5 may have a survival benefit (p < 0.0001). The NLPR cut-off for predicting early deaths and the need for massive transfusion was 3.1 (sensitivity = 80.00% and specificity = 71.05%). Conclusions: These findings suggest that blunt thoracic trauma patients exhibit distinct phenotypes of the immune response and coagulopathy from the early stages. A controlled, balanced interaction of immune, coagulation, and fibrinolytic systems might effectively achieve tissue repair and increase survival in thoracic trauma patients and should be subject to further research. Full article

RGB-D (depth) Salient Object Detection (SOD) seeks to identify and segment the most visually compelling objects within a given scene. Depth data, known for their strong discriminative capability in spatial localization, provide an advantage in achieving accurate RGB-D SOD. However, recent research in this field has encountered significant challenges due to the poor visual qualities and disturbing cues in raw depth maps. This issue results in indistinct or ambiguous depth features, which consequently weaken the performance of RGB-D SOD. To address this problem, we propose a novel pseudo depth feature generation-based RGB-D SOD Network, named PDFNet, which can generate some new and more distinctive pseudo depth features as an extra supplement source to enhance the raw depth features. Specifically, we first introduce an RGB-guided pseudo depth feature generation subnet to synthesize more distinctive pseudo depth features for raw depth feature enhancement, since the discriminative power of depth features plays a pivotal role in providing effective contour and spatial cues. Then, we propose a cross-modal fusion mamba (CFM) to effectively merge RGB features, raw depth features, and generated pseudo depth features. We adopt a channel selection strategy within the CFM module to align the pseudo depth features with raw depth features, thereby enhancing the depth features. We test the proposed PDFNet on six commonly used RGB-D SOD benchmark datasets. Extensive experimental results validate that the proposed approach achieves superior performance. For example, compared to the previous cutting-edge method, AirSOD, our method improves the F-measure by 2%, 1.7%, 1.1%, and 2.2% on the STERE, DUTLF-D, NLPR, and NJU2K datasets, respectively. Full article

Cholesterol crystal embolism (CCE) is an underrecognized multisystemic disease caused by the displacement of cholesterol crystals from atheromatous aortic plaques to distal vascular beds, leading to ischemic injury of target organs, particularly the kidneys, i.e., atheroembolic renal disease (ARD). According to recent research, cellular necrosis, induced by crystal-induced cytotoxicity, enhances the autoinflammatory cascade of the NLPR3 inflammasome, leading in turn to the so-called “necroinflammation”. The purported involvement of the latter in CCE offers a rationale for the therapeutic approach with anti-inflammatory drugs such as glucocorticoids, the use of which has long been a matter of debate in CCE. Diagnostic delay and no consistent evidence regarding efficacious treatment, leading to inconsistency in clinical practice, may worsen the already poor prognosis of ARD. The possible role of glucocorticoids in the treatment of ARD is thereby herein explored in a narrative fashion, analyzing the limited data from case reports and clinical trials. Full article

Objective: There is increasing evidence for the effect of inflammation on the etiology of febrile seizure (FS) patients. We aimed to investigate the role of easily accessible inflammatory markers such as the neutrophil–lymphocyte ratio (NLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil–lymphocyte–platelet ratio (NLPR), and pan-immune-inflammation value (PIV) in febrile seizure. Methods: A total of 300 children, including 100 with febrile convulsions (FS), 100 febrile controls (FCs), and 100 healthy controls (HCs), were included in this retrospective study. The FS group was compared with the FC and HC groups in terms of these inflammatory indexes. Results: Between the FS group and the FC group, the neutrophil count was significantly higher in the FS group (p = 0.001) and the lymphocyte count was significantly lower (p < 0.001). The NLR (p < 0.001), SII (p < 0.001), SIRI (p < 0.001), NLPR (p < 0.001), and PIV (p < 0.001) were significantly higher in the FS group than in both the FC and healthy control groups. The optimal cut-off values for predicting FS in febrile conditions were 3.59> for NLR, >870.47 for SII, >1.96 for SIRI, 0.96> for NLPR, and >532.75 for PIV. Conclusions: The inflammatory indices are inexpensive, easily accessible hematological markers that can contribute to the diagnosis of FS. Full article

Background and Objectives: Differentiation between brucella spondylodiscitis and Modic type I changes (MC1) includes difficulties. Hematological inflammatory indices (HII) such as neutrophil to lymphocyte ratio (NLR) and aggregate index of systemic inflammation (AISI) are suggested as indicators of inflammation and infection and have diagnostic, prognostic, and predictive roles in various diseases. This study aimed to evaluate differences between brucella spondylodiscitis and MC1 in terms of HII. Materials and Methods: Thirty-five patients with brucella spondylodiscitis and thirty-seven with MC1 were enrolled in the study. Brucella spondylodiscitis and MC1 were diagnosed by microbiological, serological, and radiological diagnostic tools. HII (NLR, MLR, PLR, NLPR, SII, SIRI, AISI) were derived from baseline complete blood count. Results: The two groups were similar for age (p = 0.579) and gender (p = 0.092), leukocyte (p = 0.127), neutrophil (p = 0.366), lymphocyte (p = 0.090), and monocyte (p = 0.756) scores. The Brucella spondylodiscitis group had significantly lower pain duration (p < 0.001), higher CRP and ESR levels (p < 0.001), and lower platelet count (p = 0.047) than the MC1 group. The two groups had similarity in terms of HII: NLR (p = 0.553), MLR (p = 0.294), PLR (p = 0.772), NLPR (p = 0.115), SII (p = 0.798), SIRI (p = 0.447), and AISI (p = 0.248). Conclusions: Increased HII can be used to differentiate infectious and non-infectious conditions, but this may be invalid in brucellosis. However, pain duration, CRP and ESR levels, and platelet count may be useful to distinguish brucella spondylodiscitis from MC1. Full article

Inflammasomes are multiprotein complexes that trigger processes through caspase-1 activation, leading to the maturation of proinflammatory cytokines, such as IL-1β and IL-18. The gene encoding the inflammasome stimulatory protein NLRP3 is conserved in canines. Caspase-1/4 homologues have been identified in multiple carnivores, including canines, and caspase-1 activity has been shown in humans. The NLRP3 inflammasome has also been described in some canine inflammatory diseases. Andrographolide, a labdane diterpene, is the principal active ingredient in the herb Andrographis paniculate. The objective of this study was to determine the effect of andrographolide on the gene expression of the components of the NLRP3 inflammasome, proinflammatory cytokines, and IL-1β secretion in canine peripheral blood mononuclear cells. For this, MTT assays and real-time PCR were employed to assess the cytotoxicity and gene expression. Further, an ELISA test was performed to measure the IL-1β concentration. The findings reveal that andrographolide significantly reduces the expression of NLRP3, caspase-1/4, IL-1β, and IL-18. Additionally, it decreases the secretion of IL-1β and other proinflammatory cytokines, including IL-6, IL-8, and TNF-α. The results show that andrographolide decreases the expression of NLRP3, caspase-1/4, IL-1β, and IL-18. Andrographolide also reduces proinflammatory cytokines expression, and decreases IL-1β secretion. This indicates that andrographolide can interfere with the activation and function of the inflammasome, resulting in a decrease in the inflammatory response in canines. Research in this area is still budding, and more studies are necessary to fully understand andrographolide’s mechanisms of action and its therapeutic potential in relation to the NLRP3 inflammasome in dogs. Full article

Background: Premature newborns are at a significant risk for Systemic Inflammatory Response Syndrome SIRS, a condition associated with high morbidity and mortality. This study aimed to evaluate the predictive and diagnostic capability of laboratory markers like Neutrophil to Lymphocyte Ratio (NLR), derived Neutrophil to Lymphocyte Ratio (dNLR), Platelet-to-Lymphocyte Ratio (PLR), and Neutrophil-to-Lymphocyte-to-Platelet Ratio (NLPR) in diagnosing SIRS in premature newborns. Methods: Premature newborns with and without SIRS were evaluated in a prospective design during a one-year period. Among 136 newborns, early and 72 h post-birth analyses were performed. Results: At 24 h, NLR’s cutoff value was 8.69, yielding sensitivity and specificity rates of 52.77% and 83.47% (p = 0.0429), respectively. The dNLR showed a cutoff of 5.61, with corresponding rates of 63.27% and 84.15% (p = 0.0011), PLR had a cutoff of 408.75, with rates of 51.89% and 80.22% (p = 0.1026), and NLPR displayed a cutoff of 0.24, with rates of 75.85% and 86.70% (p = 0.0002). At 72 h, notable sensitivity and specificity improvements were observed, particularly with NLPR having a cutoff of 0.17, showing sensitivity of 77.74% and specificity of 95.18% (p < 0.0001). NLR above the cutoff indicated a 33% increase in SIRS risk, with a hazard ratio (HR)of 1.33. The dNLR was associated with a twofold increase in risk (HR 2.04). NLPR demonstrated a significant, over threefold increase in SIRS risk (HR 3.56), underscoring its strong predictive and diagnostic value for SIRS development. Conclusion: Integrating these findings into clinical practice could enhance neonatal care by facilitating the early identification and management of SIRS, potentially improving outcomes for this vulnerable population. Full article

Systemic Inflammatory Response Syndrome (SIRS) is associated with significant morbidity and mortality in full-term newborns. This study aimed to evaluate the predictive value of the Neutrophil-to-Lymphocyte Ratio (NLR), Derived Neutrophil-to-Lymphocyte Ratio (dNLR), Platelet-to-Lymphocyte Ratio (PLR), Neutrophil, Lymphocyte, and Platelet Ratio (NLPR), AST-to-Platelet Ratio Index (APRI), and Systemic Immune–Inflammation Index (SII) in identifying the risk for SIRS development in full-term newborns. Conducted between January 2023 and January 2024, this observational cohort study compared full-term newborns diagnosed with SIRS with newborns without SIRS, measuring the inflammatory markers within the first day of life and three days post-birth. The study included 229 newborns, 81 with SIRS and 148 controls without SIRS. Statistically significant differences were observed in NLR (3.81 vs. 2.20, p < 0.0001), PLR (68.12 vs. 52.30, p < 0.0001), and liver enzymes (AST 40.96 U/L vs. 31.58 U/L, ALT 34.66 U/L vs. 22.46 U/L, both p < 0.0001) between the groups. The NLPR demonstrated substantial diagnostic value, with a sensitivity of 78.36% and specificity of 83.52% at 72 h (p < 0.0001). Regression analysis highlighted that the NLPR and SII were strongly predictive of SIRS, with the NLPR showing over three-times higher SIRS risk (HR 3.29, p < 0.0001) and SII indicating nearly 3.5 times the risk (HR 3.47, p < 0.0001). The NLPR, APRI, and SII showed similar prediction values to CRP levels measured on the first and third days of life (HR 3.16). Inflammatory markers like NLR, PLR, and systemic indices such as NLPR and SII, alongside liver function tests, are significant predictors of SIRS in full-term newborns. These findings support the integration of these markers into routine neonatal care, allowing for early identification and potentially improved management of newborns at risk for SIRS, thereby enhancing clinical outcomes. Full article

Microglial cells have been demonstrated to be significant resident immune cells that maintain homeostasis under physiological conditions. However, prolonged or excessive microglial activation leads to disturbances in the resolution of inflammation (RoI). Formyl peptide receptor 2 (FPR2) is a crucial player in the RoI, interacting with various ligands to induce distinct conformational changes and, consequently, diverse biological effects. Due to the poor pharmacokinetic properties of endogenous FPR2 ligands, the aim of our study was to evaluate the pro-resolving effects of a new ureidopropanamide agonist, compound AMS21, in hippocampal organotypic cultures (OHCs) stimulated with lipopolysaccharide (LPS). Moreover, to assess whether AMS21 exerts its action via FPR2 specifically located on microglial cells, we conducted a set of experiments in OHCs depleted of microglial cells using clodronate. We demonstrated that the protective and anti-inflammatory activity of AMS21 manifested as decreased levels of lactate dehydrogenase (LDH), nitric oxide (NO), and proinflammatory cytokines IL-1β and IL-6 release evoked by LPS in OHCs. Moreover, in LPS-stimulated OHCs, AMS21 treatment downregulated NLRP3 inflammasome-related factors (CASP1, NLRP3, PYCARD) and this effect was mediated through FPR2 because it was blocked by the FPR2 antagonist WRW4 pre-treatment. Importantly this beneficial effect of AMS21 was only observed in the presence of microglial FPR2, and absent in OHCs depleted with microglial cells using clodronate. Our results strongly suggest that the compound AMS21 exerts, at nanomolar doses, protective and anti-inflammatory properties and an FPR2 receptor located specifically on microglial cells mediates the anti-inflammatory response of AMS21. Therefore, microglial FPR2 represents a promising target for the enhancement of RoI. Full article