Inflammation-related Diseases Research Articles

Low-grade systemic inflammation links heavy metal exposures to mortality: A multi-metal inflammatory index approach

Certain heavy metals have been correlated to an elevated risk of inflammation-related diseases and mortality. Nevertheless, the intricate relationships between metal exposure, inflammation and mortality remain unknown. We included 3741 adults with measurements of ten urinary heavy metals in the National Health and Nutritional Examination Survey (NHANES) 2005–2010, followed up to December 31, 2019. Low-grade systemic inflammation was evaluated by various markers, including C-reactive protein (CRP) and ratios derived from regular blood tests. We assessed associations between heavy metal and all-cause mortality using multivariate COX regressions. Then we assessed the mediation effect of low-grade systemic inflammation on the associations via Sobel Test. To gauge the systemic inflammatory potential of the multi-metal mixture and its correlation with all-cause mortality, a Metal Mixture Inflammatory Index (MMII) was developed using reduced rank regression (RRR) models. The association between MMII and all-cause mortality was explored via multivariate COX regressions. Cadmium, antimony and uranium displayed positive associations with mortality, with hazard ratios (HR) ranging from 1.18 to 1.46 (all P-FDR < 0.05). Mediation analyses revealed that the associations between specific heavy metals (cadmium and antimony) and mortality risk were slightly mediated by the low-grade systemic inflammation markers, with mediation proportions ranging from 3.11 % to 5.38 % (all P < 0.05). MMII, the weighted sum of 9 heavy metals, significantly predicted platelet-to-lymphocyte ratio (PLR) and CRP (β = 0.10 and 1.16, all P < 0.05), was positively associated with mortality risk (HR 1.28, 95 % CI 1.14 to 1.43). Exposure to heavy metals might increase all-cause mortality, partly mediated by low-grade systemic inflammation. MMII, designed to assess the potential systemic inflammatory effects of exposure to multiple heavy metals, was closely related to the all-cause mortality risk. This study introduces MMII as an approach to evaluating co-exposure and its potential health effects comprehensively.

Investigation of phytochemical contents and anticancer, antioxidant, antimicrobial activities of Cucurbita pepo leaves

Ethanol and acetone extracts of Cucurbita pepo leaves were in vitro analyzed to determine the vitamin contents, antioxidant, anticancer, and antimicrobial activity of the leaves. According to HPLC analyses, the leaves contained slight amounts of vitamin C, A, and E. The analysis for antioxidant activity revealed that both ethanol and acetone extracts exhibited high activity values against ABTS+•, OH•, and DPPH• radicals. The total phenols and flavonoid assay revealed high values for the extracts. The MTT test revealed that both ethanol and acetone extracts exhibited cytotoxic activity toward human breast cancer cells (MCF-7). But no significant activities observed against hepatocellular carcinoma cells (HepG-2). The antimicrobial activity assay revealed activity of the extracts towards selected Gram's positive and Gram's negative bacteria. These results have provided scientific motivation to use Cucurbita pepo leaves as a medicinal plant to treat oxidative and inflammatory-related diseases.

Understanding of Endomucin: a Multifaceted Glycoprotein Functionality in Vascular Inflammatory-Related Diseases, Bone Diseases and Cancers.

Endomucin (MUC14), encoded by EMCN gene, is an O-glycosylated transmembrane mucin that is mainly found in venous endothelial cells (ECs) and highly expressed in type H vessels of bone tissue. Its main biological functions include promoting endothelial generation and migration through the vascular endothelial growth factor (VEGF) signaling pathway and inhibiting the adhesion of inflammatory cells to ECs. In addition, it induces angiogenesis and promotes bone formation. Due to the excellent functions of Endomucin in the above aspects, it provides a new research target for the treatment of vascular inflammatory-related diseases and bone diseases. Based on the current understanding of its function, the research of Endomucin mainly focuses on the above two diseases. As it is known, the progression of cancer is closely related to angiogenesis. Endomucin recently is found to be differentially expressed in a variety of tumors and correlated with survival rate. The biological role of Endomucin in cancer is opaque. This article introduces the research progress of Endomucin in vascular inflammatory-related diseases and bone diseases, discusses its application value and prospect in the treatment, and collects the latest research situation of Endomucin in tumors, to provide meaningful evidence for expanding the research field of Endomucin.

The Role of Mesenchymal Stem/Stromal Cells Secretome in Macrophage Polarization: Perspectives on Treating Inflammatory Diseases.

Mesenchymal stem/stromal cells (MSCs) have exhibited potential for treating multiple inflammation- related diseases (IRDs) due to their easy acquisition, unique immunomodulatory and tissue repair properties, and immune-privileged characteristics. It is worth mentioning that MSCs release a wide array of soluble bioactive components in the secretome that modulate host innate and adaptive immune responses and promote the resolution of inflammation. As the first line of defense, macrophages exist throughout the entire inflammation process. They continuously switch their molecular phenotypes accompanied by complementary functional regulation ranging from classically activated pro-inflammatory M1-type (M1) to alternatively activated anti-inflammatory M2-type macrophages (M2). Recent studies have shown that the active intercommunication between MSCs and macrophages is indispensable for the immunomodulatory and regenerative behavior of MSCs in pharmacological cell therapy products. In this review, we systematically summarized the emerging capacities and detailed the molecular mechanisms of the MSC-derived secretome (MSC-SE) in immunomodulating macrophage polarization and preventing excessive inflammation, providing novel insights into the clinical applications of MSC-based therapy in IRD management.

Phytochemical screening and anti-inflammatory activities of different fractions from Citrullus lanatus leaves: A comprehensive study

Inflammation, a protective immune response, can contribute to maintaining homeostasis but can also cause harm when chronic or excessive. Citrullus lanatus has been suggested to possess antioxidant and anti-inflammatory activities that may aid in preventing and treating oxidative stress and inflammation. The main objective of this study was to evaluate the levels of phytochemicals, as well as the antioxidant and anti-inflammatory activities of Citrullus lanatus leaves extract. The ethyl acetate, hexane, butanol fraction and aqueous methanol extract were subjected to various standard quantitative phytochemical analysis, while the hexane fraction and aqueous methanol extract were subjected to standard in vitro anti-inflammatory assays. Spectrophotometric and gravimetric methods were used in this study. The in vitro anti-denaturation (stabilization) assay was used for detecting a wide range of antioxidant compounds. The ethyl acetate fraction had the highest flavonoid and polyphenol levels, followed by hexane, butanol, and aqueous methanol extract, respectively. Quantitative phytochemical analysis showed the levels of flavonoids, polyphenols, tannins, alkaloids and saponins present in the different fractions of C. lanatus. The human erythrocyte membrane stabilization assay showed that extracts were able to stabilize human red blood cell membrane against hypotonic-induced hemolysis in five different samples. The extract of Citrullus lanatus was found to have the highest antioxidant activity. This study has shown that the leaves of Citrullus lanatus can be used in ethnomedicine for the prevention and treatment of ailments caused by oxidative stress and inflammation-related diseases.

Polyvinylpyrrolidone-curcumin nanoparticles with immune regulatory and metabolism regulatory effects for the treatment of experimental autoimmune uveitis

Uveitis comprises a cluster of intraocular inflammatory disorders characterized by uncontrolled autoimmune responses and excessive oxidative stress leading to vision loss worldwide. In the present study, curcumin (CUR) was conjugated with polyvinylpyrrolidone (PVP) to form PVP-CUR nanoparticles with significantly elevated solubility and outstanding multiple radical scavenging abilities. In vitro studies revealed that PVP-CUR nanoparticles markedly mitigated oxidative stress and reduced apoptosis in a H2O2-induced human retinal pigment epithelial cell line (ARPE-19) and promoted phenotypic polarization from M1 to M2 in an LPS-induced human microglial cell line (HMC3). Further in vivo studies demonstrated the prominent therapeutic effects of PVP-CUR nanoparticles on experimental autoimmune uveitis (EAU), which relieved clinical and pathological progression, improved perfusion and tomographic manifestations of retinal vessels, and reduced blood–retinal barrier (BRB) leakage; these effects may be mediated by mitigating oxidative stress and attenuating macrophage/microglia-elicited inflammation. Notably, treatment with PVP-CUR nanoparticles was shown to regulate metabolite alterations in EAU rats, providing novel insights into the underlying mechanisms involved. Additionally, the PVP-CUR nanoparticles showed great biocompatibility in vivo. In summary, our study revealed that PVP-CUR nanoparticles may serve as effective and safe nanodrugs for treating uveitis and other oxidative stress- and inflammation-related diseases.

Antidepressant Effect of Heracleum moellendorffii Extract on Behavioral Changes in Astrocyte Ablation Mouse Model of Depression by Modulating Neuroinflammation through the Inhibition of Lipocalin-2.

Astrocyte dysfunction and inflammation play a pivotal role in depression. In this study, we evaluated the antidepressant properties of Heracleum moellendorffii root extract (HME), which is traditionally used for inflammation-related diseases, in a mouse model with astrocyte depletion that resembles the prefrontal cortex pathology of depressive patients. Mice were divided into four groups, with 10 mice per group. To induce astrocyte ablation in the mice's prefrontal cortex (PFC), we used astrocytic toxin L-alpha-aminoadipic acid (L-AAA) and administered HME orally at 200 and 500 mg/kg for 22 days. We utilized the tail suspension test (TST) to assess depression-like behaviors and the open field test (OFT) to evaluate anxiety-like activities. Additionally, astrocytic and inflammatory markers in the PFC were evaluated using immunohistochemistry and ELISA. The results showed that infusion of L-AAA significantly decreased the expression of astrocytic glial fibrillary acidic protein (GFAP), which was accompanied by increased depression and anxiety-like behaviors. However, HME significantly reversed these effects by dose-dependently enhancing GFAP expression and modulating inflammatory markers, such as TNF-α, IL-6, and particularly lipocalin-2, a master proinflammatory mediator. These results imply that HME contributes to the alleviation of depression and anxiety-like behaviors by promoting astrocyte recovery and reducing neuroinflammation, especially through lipocalin-2 inhibition.

Anti-inflammatory in vitro activities of eleven selected caffeic acid derivatives based on a combination of pro−/anti-inflammatory cytokine secretions and principal component analysis – A comprehensive evaluation

Eleven compounds including caffeic acid (CA), 4 kinds of caffeoylquinic acid (CQA) and 6 kinds of dicaffeoylquinic acid (DCQA), were selected to evaluate the anti-inflammatory effectiveness using mouse primary peritoneal macrophages in the absence or presence of lipopolysaccharide (LPS). The optimal non-cytotoxic doses of each individual compound were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Pro-inflammatory (TNF-α, IL-1β, IL-6) and anti-inflammatory (IL-10) cytokines secreted by treated macrophages were analyzed using the enzyme-linked immunosorbent assay. Cytokine secretion profiles of each individual test sample at optimal non-cytotoxic doses were further analyzed using Principal Component Analysis (PCA). The results showed that CA and all selected CQAs exhibited lower cytotoxicity (IC50: >50 μmol/l). Both CA and 5-CQA were found to have the most significant contributions for inhibiting pro-inflammatory cytokines, but increasing anti-inflammatory cytokine secretions, evidencing that CA at 10 μmol/l and 5-CQA at 25 μmol/l can be qualified as potent anti-inflammatory agents for treating inflammation-related diseases.

Acute exercise activates the AHR in peripheral blood mononuclear cells in an intensity-dependent manner.

The kynurenine pathway (KP) of tryptophan degradation generates several metabolites such as kynurenine (KYN) or kynurenic acid (KA) that serve as endogenous ligands of the aryl hydrocarbon receptor (AHR). Due to its distinct biological roles particularly modulating the immune system, the AHR is a current therapeutic target across different inflammation-related diseases. Here, we show an acute exercise-induced increase in AHR ligand availability on a systemic level and a kynurenine pathway activation in peripheral blood mononuclear cells (PBMCs). Concurrently, the AHR is activated in PBMCs following acute exercise. Exercise effects on both, kynurenic acid and AHR activation in PBMCs were greater in response to high-intensity interval exercise (HIIE) (50 min, six 3-min intervals at 90% V̇o2peak, and 3-min intervals at 50% V̇o2peak in between) compared with workload-matched moderate-intensity continuous exercise (MICE) (50 min). In conclusion, these data indicate a novel mechanistic link in how exercise modulates the immune system through the kynurenine pathway-AHR axis, potentially underlying exercise-induced benefits in various chronic diseases.NEW & NOTEWORTHY The findings of this study show that acute endurance exercise activates a receptor that has been described to integrate metabolic signals into the immune system. We uncover a potential mechanistic link on how exercise modulates the immune system through the kynurenine pathway-AHR axis, potentially underlying exercise-induced benefits in various chronic diseases and of relevance for other cell types.

Capture and Storage of Cell-Free DNA via Bio-Informational Hydrogel Microspheres.

Excessive cell-free DNA (cfDNA) can induce chronic inflammation by activating intracellular nucleic acid sensors. Intervention in cfDNA-mediated "pro-inflammatory signaling transduction" could be a potential alleviating strategy for chronic inflammation, such as in diabetic wounds. However, effectively and specifically downgrading cfDNA concentration in the pathological microenvironment remains a challenge. Therefore, this work prepares free-standing polydopamine nanosheets through DNA-guided assembly and loaded them into microfluidic hydrogel microspheres. The π─π stacking/hydrogen bonding interactions between polydopamine nanosheets and the π-rich bases of cfDNA, along with the cage-like spatial confinement created by the hydrogel polymer network, achieved cfDNA capture and storage, respectively. Catechol in polydopamine nanosheets can also assist in reducing reactive oxygen species (ROS) levels. Efficient cfDNA binding independent of serum proteins, specific interdiction of abnormal activation of cfDNA-associated toll-like receptor 9, as well as down-regulation of inflammatory cytokines and ROS levels are shown in this system. The chronic inflammation alleviating and the pro-healing effects on the mice model with diabetic wounds are also investigated. This work presents a new strategy for capturing and storing cfDNA to intervene in cell signaling transduction. It also offers new insights into the regulatory mechanisms between inflammatory mediators and biomaterials in inflammation-related diseases.

An active peptide from yak inhibits hypoxia-induced lung injury via suppressing VEGF/MAPK/inflammatory signaling

Pulmonary vascular remodeling and inflammation play an important role in the hypoxic-induced lung diseases. Our previous investigations showed that peptide from yak milk residues could alleviate inflammation. In this study, our results suggest that peptide (LV) from yak milk residues peptide had protective effect of lung in the animal models of hypoxic-induced lung injury. LV Gavage could improve pulmonary vascular remodeling in the lung tissues of hypoxic mice. A comprehensive analysis of metabolomics and transcriptomics revealed that 5-KETE, 8,9-EET, and 6-keto-prostaglandin F1a might be potential targets to prevent lung injury in the hypoxic mice. These metabolites can be regulated by MAPK/VEGF and inflammatory pathways. Our data indicated that LV treatment could inhibit apoptosis and inflammation via Nrf2/NF-κB/MAPK/PHD-2 pathway and protected hypoxic-induced lung epithelial cells injury. Taken together, our results suggest that LV provides a novel therapeutic clue for the prevention of hypoxia-induced lung injury and inflammation-related lung diseases.

Unraveling the Pharmacological Intricacies of Kurarinone in Osteoporosis: Insights from a Network Pharmacology Approach

Background Kurarinone, a compound derived from Sophora flavescens, has been widely studied for its anti-inflammatory properties, as well as its potential in treating autoimmune encephalomyelitis and inflammation-related musculoskeletal diseases. However, the specific molecular mechanisms by which Kurarinone affects osteoporosis are still not fully understood. Objectives To explore the potential pharmacological targets and molecular mechanisms underlying the therapeutic effects of Kurarinone on osteoporosis. Materials and Methods To confirm the impact of Kurarinone on osteoporosis, network pharmacology techniques were used to analyze the mechanisms of Kurarinone on osteoporosis. Molecular docking was performed to examine the binding of Kurarinone to key targets involved in osteoporosis. Then, we conducted TRAcP staining, quantitative polymerase chain reaction (q-PCR), and Western blot experiments to validate the results. Results Utilizing network pharmacology approaches coupled with docking analysis, our investigation revealed that Kurarinone was involved in the osteoclast differentiation and MAPK signaling pathways. According to in vitro experiments, Kurarinone was found to inhibit osteoclast formation through the p38/MAPK pathway. Conclusion This study suggests that Kurarinone may treat osteoporosis by inhibiting MAPK phosphorylation and inhibiting osteoclast formation.

Schistosoma japonicum cystatin alleviates paraquat poisoning caused acute lung injury in mice through activating regulatory macrophages

BackgroundParaquat (PQ) is a widely used herbicide that poisons human by accident or intentional ingestion. PQ poisoning causes systemic inflammatory response syndrome (SIRS) resulting in acute lung injury (ALI) with an extremely high mortality rate. Blood trematode Schistosoma japonicum-produced cystatin (Sj-Cys) is a strong immunomodulatory protein that has been experimentally used to treat inflammation related diseases. In this study, Sj-Cys recombinant protein (rSj-Cys) was used to treat PQ-induced lung injury and the immunological mechanism underlying the therapeutic effect was investigated. MethodsPQ-induced acute lung injury mouse model was established by intraperitoneally injection of 20 mg/kg of paraquat. The poisoned mice were treated with rSj-Cys and the survival rate was observed up to 7 days compared with the group without treatment. The pathological changes of PQ-induced lung injury were observed by examining the histochemical sections of affected lung tissue and the wet to dry ratio of lung as a parameter for inflammation and edema. The levels of the inflammation related cytokines IL-6 and TNF-α and regulatory cytokines IL-10 and TGF-β were measured in sera and in affected lung tissue using ELISA and their mRNA levels in lung tissue using RT-PCR. The macrophages expressing iNOS were determined as M1 and those expressing Arg-1 as M2 macrophages. The effect of rSj-Cys on the transformation of inflammatory M1 to regulatory M2 macrophages was measured in affected lung tissue in vivo (EKISA and RT-PCR) and in MH-S cell line in vitro (flow cytometry). The expression levels of TLR2 and MyD88 in affected lung tissue were also measured to determine their role in the therapy of rSj-Cys on PQ-induced lung injury. ResultWe identified that treatment with rSj-Cys significantly improved the survival rate of mice with PQ-induced lung injury from 30 % (untreated) to 80 %, reduced the pathological damage of poisoning lung tissue, associated with significantly reduced levels of proinflammatory cytokines (IL-6 from 1490 to 590 pg/ml, TNF-α from 260 to 150 pg/ml) and increased regulatory cytokines (IL-10 from360 to 550 pg/ml, and TGF-β from 220 to 410 pg/ml) in both sera (proteins) and affected lung tissue (proteins and mRNAs). The polarization of macrophages from M1to M2 type was found to be involved in the therapeutic effect of rSj-Cys on the PQ-induced acute lung injury, possibly through inhibiting TLR2/MyD88 signaling pathway. ConclusionsOur study demonstrated the therapeutic effect of rSj-Cys on PQ poisoning caused acute lung injury by inducing M2 macrophage polarization through inhibiting TLR2/MyD88 signaling pathway. The finding in this study provides an alternative approach for the treatment of PQ poisoning and other inflammatory diseases.

Novel Mechanism of SIRT3 Regulation in Cardiac Inflammatory Injury: The Key Role of MITOL

Background: Myocardial injury is a common heart disease that involves various forms of cell death, including pyroptosis. Lipopolysaccharide (LPS) can simulate the inflammatory response of cardiomyocytes, resulting in their damage. Sirtuin 3 (SIRT3), a mitochondrial deacetylase, has been shown to play a role in cardiac protection. This study aimed to investigate whether SIRT3 mitigates inflammation-induced cardiomyocyte pyroptosis and alleviates LPS-induced myocardial injury via the mitochondrial ubiquitin ligase (MITOL)-dependent mechanism. Methods: Mouse and H9C2 cardiomyocyte models were used to simulate myocardial inflammatory injury by LPS treatment. Cardiac ultrasound, protein expression analysis, mRNA expression detection, and serum biochemical indicators were used to assess the extent of myocardial injury. The EdU experiment was conducted to detect cell proliferation capacity. DCFH-DA fluorescence was used to measure Reactive Oxygen Species (ROS) levels. JC-1 probe analysis was used to assess the aggregate/monomer ratio in different treatment groups. Furthermore, SIRT3 treatment and MITOL silencing experiments were conducted to explore the impact of SIRT3 on cardiomyocyte pyroptosis and whether it functions through MITOL. Scanning electron microscopy experiments were conducted to assess the reversal of the protective effect of SIRT3 by silencing MITOL. Results: The experimental results showed that LPS treatment significantly impaired mouse cardiac function, increased the expression of pyroptosis-related proteins in cardiomyocytes, elevated serum myocardial injury indicators, and increased the mRNA expression of inflammatory factors (tumor necrosis factor-alpha (TNFα) and interleukin-1β (IL-1β)). SIRT3 treatment significantly reduced LPS-induced myocardial injury, improved cardiac function, reduced the expression of pyroptosis-related proteins, and decreased inflammatory factors. Silencing MITOL reversed the protective effect of SIRT3 on cardiomyocyte injury, suggesting that SIRT3 exerted its therapeutic effect through MITOL. Conclusion: This study revealed that SIRT3 mitigated inflammation-induced cardiomyocyte pyroptosis via a MITOL-dependent mechanism, thereby alleviating LPS-induced myocardial injury. This finding provides a new molecular target for the treatment of myocardial inflammation-related diseases and lays a theoretical foundation for the development of cardiac protection strategies. Future research can further explore the potential application of the SIRT3-MITOL axis in cardiac diseases, providing effective treatment methods for cardiac patients.

Associations between common contraceptive use and circulating inflammatory biomarkers.

Ovarian cancer incidence has declined in recent decades, due in part to oral contraceptive (OC) use and tubal ligation. However, intrauterine device (IUD) use has increasingly replaced OC use. As ovarian cancer is an inflammation-related disease, we examined the association of OC use, IUD use, and tubal ligation with plasma levels of C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor α receptor 2 (sTNFR2), in the Nurses' Health Study (NHS) and NHSII. After adjusting for reproductive, hormonal, and lifestyle factors, and mutual adjustment for other methods of contraception, there were no differences in inflammatory markers between ever and never use of each method. However, CRP levels decreased from an average 30.4% (-53.6, 4.4) with every 5 years since initial IUD use (P-trend=0.03), while CRP increased an average 9.9% (95% CI: 5.7, 14.3) with every 5 years of use of OC (P-trend<0.0001) as well as differences by BMI and menopausal status. Our results suggest IUD use and tubal ligation are not associated with higher circulating inflammatory markers long term, although long duration of OC use may increase generalized inflammation, which may in part explain why its protective effect wanes over time.

A Single-Cell Transcriptome Profiling of Triptolide-Induced Nephrotoxicity in Mice.

Triptolide (TP), an active component isolated from the traditional Chinese herb Tripterygium wilfordii Hook F (TWHF), shows great promise for treating inflammation-related diseases. However, its potential nephrotoxic effects remain concerning. The mechanism underlying TP-induced nephrotoxicity is inadequately elucidated, particularly at single-cell resolution. Hence, single-cell RNA sequencing (scRNA-seq) of kidney tissues from control and TP-treated mice is performed to generate a thorough description of the renal cell atlas upon TP treatment. Heterogeneous responses of nephron epithelial cells are observed after TP exposure, attributing differential susceptibility of cell subtypes to excessive reactive oxygen species and increased inflammatory responses. Moreover, TP disrupts vascular function by activating endothelial cell immunity and damaging fibroblasts. Severe immune cell damageand the activation of pro-inflammatory Macro_C1 cells are also observed with TP treatment. Additionally, ligand-receptor crosstalk analysis reveals that the SPP1 (osteopontin) signaling pathway targeting Macro_C1 cells is triggered by TP treatment, which may promote the infiltration of Macro_C1 cells to exacerbate renal toxicity. Overall, this study provides comprehensive information on the transcriptomic profiles and cellular composition of TP-associated nephrotoxicity at single-cell resolution, which can strengthen the understanding of the pathogenesis of TP-induced nephrotoxicity and provide valuable clues for the discovery of new therapeutic targets to ameliorate TP-associated nephrotoxicity.

A near-infrared lysosomal probe for dynamic sulfur dioxide monitoring in inflammation

Inflammation is a complex physiological response involving various cellular and molecular events. Sulfur dioxide (SO2), recognized as both an endogenous signaling molecule and anti-inflammatory agent, plays a crucial role in modulating inflammation and maintaining cellular homeostasis. To gain deeper insights into the dynamics of inflammation-related processes, real-time monitoring of SO2 concentrations within cellular organelles is imperative. Here, we developed a near-infrared fluorescent probe, R2, equipped with lysosomal targeting features. R2 effectively monitors dynamic SO2 concentration changes during inflammation. The fluorescence intensity at 703 nm of R2 shows a strong linear correlation with the concentration of SO2, displaying a rapid response time to SO2 within 10 s and maintaining excellent photostability. The successful application of R2 in elucidating dynamic SO2 concentration changes in lysosomal during cellular and rat inflammatory processes underscores its significant potential as a tool for understanding the pathogenesis of inflammation-related diseases.

Characterization of the Volatilomic Fingerprint of Culinary Aromatic Herbs: A Comparative Study Based on Chemometric Analysis

Culinary aromatic herbs (CAHs), used worldwide for culinary and industrial purposes, are recognized for their wide range of beneficial health effects including antimicrobial, antioxidant, anti-hyperlipidemic, anti-inflammatory, anti-type 2 diabetes mellitus, antitumorigenic and anticarcinogenic, and anti-hypertensive properties, in addition to glucose- and cholesterol-lowering activities as well as properties that affect mental health and cognition via their phytochemical constituents, such as polyphenols (flavonoids and non-flavonoids), sulfur- and nitrogen-containing compounds, alkaloids, minerals, and vitamins. Moreover, the volatile organic metabolites (VOMs) found in CAHs offer unique analytical biosignatures linked to their sensory qualities and organoleptic characteristics. This study aimed to establish the volatilomic pattern of CAHs commonly used in Europe and in the Mediterranean region, oregano (Origanum vulgare L.) and two savory species: savory (Satureja hortensis L.) and lemon savory (Satureja montana L. var. citriodora). The volatilomic pattern of CAHs was established using headspace solid-phase microextraction (HS-SPME) followed by gas chromatography–mass spectrometry (GC-MS) determination. This is a powerful strategy to unravel the potential health benefits related to the most important VOMs identified in each aromatic herb. This comprehensive understanding will aid in establishing the authenticity of these herbs, while also safeguarding against possible fraudulent activities and adulterations. A total of 112 VOMs from different chemical families were identified. Terpenoids amounted to the major chemical family in the investigated aromatic herbs accounting for 96.0, 95.1, and 79.7% of the total volatile composition for savory, lemon savory, and oregano, respectively. Apart from contributing to flavor profiles, certain identified VOMs also possess bioactive properties, opening interesting avenues for potential application in the food, pharmaceutical, and cosmetic sectors. The volatilomic pattern combined with unsupervised principal component analysis facilitated the differentiation of the aromatic herbs under investigation, revealing the most related VOMs in each sample, which can be used as markers for the authentication of these valuable aromatic herbs, such as caryophyllene oxide (103), camphene (6), p-cymene (23), and borneol (74), among others. In addition, some VOMs have a high influence on the aromatic herb’s bioactive potential, helping to prevent certain diseases including cancer, inflammatory-related diseases, diabetes, and cardiovascular diseases.

Salivary calprotectin and neutrophils in inflammatory bowel disease in relation to oral diseases

AbstractObjectiveCalprotectin is elevated in saliva from inflammatory bowel disease (IBD) patients, but it is also affected by oral disease. We assessed the salivary concentration of calprotectin in IBD patients, in relation to intestinal and oral diseases. Furthermore, we investigated the phenotype of salivary neutrophils from IBD patients, and their ability to secrete calprotectin.Materials and MethodsThirty IBD patients and 26 controls were orally examined and sampled for stimulated saliva. Twenty‐five IBD patients provided fresh fecal samples. Calprotectin concentrations in saliva and feces were determined by an enzyme‐linked immunosorbent assay. Expression of CD11b, CD15, and CD16 on oral neutrophils was assessed by flow cytometry. Secretion of calprotectin was evaluated in cultured oral neutrophils.ResultsCalprotectin was significantly elevated in saliva of IBD patients compared to controls, particularly in Crohn's disease, irrespective of caries or periodontitis. Salivary calprotectin did not correlate to fecal calprotectin. CD11b expression was significantly reduced in salivary neutrophils from IBD patients. Salivary neutrophils from IBD patients tended to secrete more calprotectin than controls.ConclusionsSalivary calprotectin is elevated in IBD regardless of oral diseases. Furthermore, salivary neutrophils secrete calprotectin, and display lower CD11b expression in IBD.

Proteomic Analysis of Signaling Pathways Modulated by Fatty Acid Binding Protein 5 (FABP5) in Macrophages.

Although acute inflammation serves essential functions in maintaining tissue homeostasis, chronic inflammation is causally linked to many diseases. Macrophages are a major cell type that orchestrates inflammatory processes. During inflammation, macrophages undergo polarization and activation, thereby mobilizing pro-inflammatory and anti-inflammatory transcriptional programs that regulate ensuing macrophage functions. Fatty acid binding protein 5 (FABP5) is a lipid chaperone highly expressed in macrophages. FABP5 deletion is implicated in driving macrophages toward an anti-inflammatory phenotype, yet signaling pathways regulated by macrophage-FABP5 have not been systematically profiled. We leveraged proteomic and phosphoproteomic approaches to characterize pathways modulated by FABP5 in M1 and M2 polarized bone marrow-derived macrophages (BMDMs). Stable isotope labeling by amino acids-based analysis of M1 and M2 polarized wild-type and FABP5 knockout BMDMs revealed numerous differentially regulated proteins and phosphoproteins. FABP5 deletion impacted downstream pathways associated with inflammation, cytokine production, oxidative stress, and kinase activity. Toll-like receptor 2 (TLR2) emerged as a novel target of FABP5 and pharmacological FABP5 inhibition blunted TLR2-mediated activation of downstream pathways, ascribing a novel role for FABP5 in TLR2 signaling. This study represents a comprehensive characterization of the impact of FABP5 deletion on the proteomic and phosphoproteomic landscape of M1 and M2 polarized BMDMs. Loss of FABP5 altered pathways implicated in inflammatory responses, macrophage function, and TLR2 signaling. This work provides a foundation for future studies seeking to investigate the therapeutic potential of FABP5 inhibition in pathophysiological states resulting from dysregulated inflammatory signaling. SIGNIFICANCE STATEMENT: This research offers a comprehensive analysis of fatty acid binding protein 5 (FABP5) in macrophages during inflammatory response. The authors employed quantitative proteomic and phosphoproteomic approaches to investigate this utilizing bone marrow-derived macrophages that were M1 and M2 polarized using lipopolysaccharide with interferon γ and interleukin-4, respectively. This revealed multiple pathways related to inflammation that were differentially regulated due to the absence of FABP5. These findings underscore the potential therapeutic significance of macrophage-FABP5 as a candidate for addressing inflammatory-related diseases.