This research explores the impact of structural variations in laminarins derived from seaweed on their immunomodulatory properties. Laminarins from Laminaria digitata, L. hyperborea, and Saccharina latissima, were obtained using a two-step water extraction protocol, followed by structural characterization by FT-IR spectroscopy, 1H NMR, and MALDI-TOF MS. The laminarin backbones were confirmed as β-1,3-linked glucans with species-specific percentages of β-1,6-linkages (~10 %, ~4 %, and ~21 %, respectively). Each polymer chain consists of approximately 24 to 25 monomer units, while oligosaccharide fractions, produced using the enzyme LPHase, displayed distinct DP-ranges, degrees of β-1,6-branching and intrachain linkages. Laminarin from L. hyperborea and specific oligosaccharide fractions from L. hyperborea and S. latissima influenced cytokine secretion by dendritic cells (DCs). L. hyperborea laminarin and the fraction LhF5 (DP5-DP8) stimulated increased IL-6 and IL-10 secretion by DCs, suggesting a dual role in promoting inflammation and regulating the immune response. In contrast, LhF5, LhF4 (DP6-DP10), and S. latissima laminari-oligosaccharide fraction SlF3 (DP6-DP9) caused decreased TNFα secretion, reflecting anti-inflammatory potential. Co-culturing of treated DCs and CD4+ T-cells showed that L. hyperborea laminarin caused increased IL-17 and IL-10 secretion, whereas SlF3 caused reduced IL-12p40 and IFN-γ secretion. These findings show that DC maturation and T-cell activation are affected by laminarins of certain size-distribution and branching, implying therapeutic potential for the treatment of inflammatory diseases or vaccine enhancement.

Translocator protein 18 kDa (TSPO) has been a salient target for probing and monitoring inflammation in the central nervous system (CNS) and peripheral systems. Leveraging our previously developed, TSPO specific, modified acetamidobenzoxazolone derivative, the present work describes the synthesis and development of an optical probe for lung inflammation imaging: 2-(3,6-dihydroxy-9H-xanthen-9-yl)-5-(3-(3-(2-(methyl(phenyl)amino)-2-oxoethyl)-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)thioureido)benzoic acid (FITC-MBP). The FITC-MBP is prepared through facile methodology by conjugating MBP to fluorophore dye FITC. Spectral properties remained equivalent to FITC dye with absorption and emission wavelength at 486 and 520 nm, respectively. Cellular uptake studies established overexpression of TSPO in lipopolysaccharide (LPS)-induced inflammation in H1299 lung cells. Reduced mean fluorescence intensity (MFI) during blocking experiments with PK11195 in flow cytometry suggests the specificity of the fluorescent probe towards TSPO. In-vivo optical imaging analysis on LPS-induced lung-inflamed balb/c mice revealed major sequestration of FITC-MBP in the lungs compared to control at 25 min post-injection that significantly decreased on pretreatment with PK11195 due to competitive binding to TSPO. On ground of these findings, we believe the novel fluorescent probe (FITC-MBP) might be utilized to visualize the overexpressed TSPO.

Rhizomes of Curcuma wanenlueanga Saensouk, Thomudtha & Boonma have been used in Thai traditional medicine and are included as an ingredient in a Thai traditional liniment formula listed by the Ministry of Public Health of Thailand for treating symptoms related to joints and muscle inflammation. However, anti-inflammatory activity and bioactive constituents of C. wanenlueanga have not yet been investigated. Thus, this study aimed to investigate the anti-inflammatory activity and underlying mechanism of C. wanenlueanga rhizome extract and its responsible bioactive components.

The fractionation of bioactive compounds from C. wanenlueanga extract was guided by antioxidant activity on DPPH and Griess assays, and anti-inflammatory activity on LPS-induced RAW 264.7 cells. The biological activities of isolated compounds were first predicted by network pharmacology and further confirmed in cell-based assay with LPS-induced RAW 264.7 cells and enzyme-linked immunosorbent assay (ELISA) of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6).

The ethanolic extract of C. wanenlueanga rhizomes was proved to show anti-inflammatory activity on LPS-induced RAW 264.7 cells. Three curcuminoids including curcumin (1), demethoxycurcumin (2), dihydrodemethoxycurcumin (3), and two sesquiterpenoids, namely curcumenone (4), and zedoarondiol (5) were separated from anti-inflammatory fractions of C. wanenlueanga extract. The anti-inflammatory activity of these compounds to attenuate the productions of TNF-α and IL-6 was predicted by pharmacological network. The inflammatory assays, including the Griess assay for NO and ELISA for TNF-α and IL-6, confirmed that all isolated compounds reduced the production of these inflammatory mediators.

The present study shows the accordance between the results from pharmacological network and cell-based assays, which indicate the anti-inflammatory activity of C. wanenlueanga rhizomes and their bioactive constituents. This suggests the potential of bioactive compounds 1-5 to be used for quality assessment of C. wanenlueanga extract in the development of herbal products.

Pseudomonas aeruginosa is a prevalent opportunistic Gram-negative bacterial pathogen. One of its key virulence factors is pyocyanin, a redox-active phenazine secondary metabolite that plays a crucial role in the establishment and persistence of chronic infections. This review provides a synopsis of the mechanisms through which pyocyanin exacerbates pulmonary infections. Pyocyanin induces oxidative stress by generating reactive oxygen and nitrogen species which disrupt essential defense mechanisms in respiratory epithelium. Pyocyanin increases airway barrier permeability and facilitates bacterial invasion. Pyocyanin also impairs mucociliary clearance by damaging ciliary function, resulting in mucus accumulation and airway obstruction. Furthermore, it modulates immune responses by promoting the production of pro-inflammatory cytokines, accelerating neutrophil apoptosis, and inducing excessive neutrophil extracellular trap formation, which exacerbates lung tissue damage. Additionally, pyocyanin disrupts macrophage phagocytic function, hindering the clearance of apoptotic cells and perpetuating inflammation. It also triggers mucus hypersecretion by inactivating the transcription factor FOXA2 and enhancing the IL-4/IL-13-STAT6 and EGFR-AKT/ERK1/2 signaling pathways, leading to goblet cell metaplasia and increased mucin production. Insights into the role of pyocyanin in P. aeruginosa infections may reveal potential therapeutic strategies to alleviate the severity of infections in chronic respiratory diseases including cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).

Chronic aberrant inflammation is a crucial step in mediating cerebrovascular and neurodegenerative pathologies, including Alzheimer's and Parkinson's disease. Due to their exceptional antioxidant properties and ability to alter imbalance metabolism and reactive inflammation response, cocoa-derived flavanols are being investigated as potential bioactive substances to modulate and reverse these inflammation-associated disorders.

The present study will focus on the possible beneficial effects of cocoa-derived extract, enhanced with other bioactive phytochemicals such as spirulina and pineapple, on selected biomarkers of the inflammatory, metabolic, and neurodegenerative processes.

A mice model of inflammation was treated with cocoa-derived extract cocktail, and biomolecular data was obtained by performing immunohistochemical and biochemical analysis.

Results show that the cocoa-derived extract mitigates the neuroinflammatory processes triggered (decreased expression of macrophage CD11b) and prevents the escalade of subsequent neurodegeneration pathologies.

The results based on hypo-vitaminosis, neuroinflammation, and inmunoreactive analysis suggest that cocoa-derived extract is a powerful bioproduct for ameliorating neuroinflammatory processes that mediate metabolic and cerebrovascular diseases.

A bioassay-guided phytochemical study of the fruits of Cornus officinalis led to the isolation of six new iridoid glycoside dimers, named corndiridoside A-F (1-6), along with 11 analogs (7-17). The structure of these dimers was elucidated using HRESIMS, 1D and 2D NMR, IR, and UV spectra, as well as literature comparisons. The anti-inflammatory activity of all compounds was evaluated, revealing a significant inhibitory effect on all dimers on the production of NO in LPS-stimulated RAW 264.7 cells at concentrations of 25 and 50 μM. Of the six, compounds 2 and 3 showed the strongest anti-inflammatory activity.

Neuroinflammatory processes are directly involved in the pathogenesis of non-suicidal self-injury (NSSI) among adolescents. However, their role in predicting the outcome of adolescent NSSI is unknown. This study aimed to explore the relationship between inflammatory cytokines and their effect on NSSI treatment through a prospective investigation.

Thirty-two healthy adolescents and 199 adolescents who had engaged in NSSI were recruited. Blood samples were obtained from all participants to determine the concentration of inflammatory cytokines at enrollment. Thereafter, the NSSI group completed surveys on their NSSI behaviors after 3, 6, and 12 months. The outcomes of their NSSI behaviors were evaluated using the indexes of NSSI number and NSSI impulsivity.

The results showed that the mean NSSI number and NSSI impulsivity of the participants both showed a decline tendency over time. However, regarding the NSSI number, the significant treatment effect only emerged after 6 months. The abnormal rates of IL-1βand IL-8 levels of the NSSI group were significantly higher than those of healthy controls (χ2 = 3.945, 27.394; P < 0.05). In the regression models, high IL-8 level (β: 0.225, 95% CI: 0.001, 0.005; p = 0.001), high TNF-α level (β: 0.157, 95% CI: 0.023, 0.244; p = 0.018), and low IL-10 level (β: - 0.261, 95% CI: - 2.678, - 0.901; p = 0.017) could predict the treatment effect of NSSI number. High level of IL-8 (β: 0.233, 95% CI: 0.002, 0.009; p = 0.001) and long duration of medical treatment (β: 0.285, 95% CI: 0.234, 0.649; p < 0.001) could predict the treatment effect of NSSI impulsivity. When considering the two indexes together, the role of screened-out cytokines, IL-8 (OR = 1.065, 95% CI: 1.032,1.099; p < 0.001), TNF-α (OR = 1.839, 95% CI: 1.063, 3.182; p = 0.029) and IL-10 (OR = 0.031, 95% CI: 0.002, 0.541; p = 0.017), were still stable.

Employing the assessment of inflammatory cytokines among adolescents who engage in NSSI may be helpful in predicting their treatment outcome and designing other suitable treatment schemes in advance.

registered in https://www.medicalresearch.org.cn/ . Retrospectively registered: registered in https://www.chictr.org.cn/ .

ChiCTR2500097375. Date of registration: 18th February, 2025.

Periostin regulates angiogenesis, inflammation, and fibrosis, key processes in the pathophysiology of rheumatic diseases (RDs). However, its association with RDs has not been assessed. We conducted a systematic review and meta-analysis of studies reporting circulating periostin in RD patients and healthy controls. We searched electronic databases from inception to 30 November 2024 for relevant articles and assessed the risk of bias and the certainty of evidence using the JBI critical appraisal checklist and GRADE, respectively. In 12 eligible studies, there was a non-significant trend towards higher periostin concentrations in RD patients (standard mean difference, SMD = 0.46, 95% CI -0.07 to 0.98, p = 0.089; I2 = 94.2%, p < 0.001). The results were stable in sensitivity analysis. There were no significant associations between the SMD and age, male-to-female ratio, number of participants, or publication year. However, we observed significant periostin elevations in studies investigating systemic sclerosis and rheumatoid arthritis but not osteoarthritis. Significant periostin reductions were observed in studies investigating ankylosing spondylitis and dermatomyositis. Furthermore, the SMD was significant in studies conducted in America, but not Asia or Europe. Our study suggests significant periostin elevations in rheumatoid arthritis and systemic sclerosis. Such elevations may reflect a more pronounced dysregulation of angiogenesis and fibrosis when compared to other RDs. Further research is warranted to investigate periostin concentrations in a wide range of RDs with various inflammatory, angiogenic, and fibrotic features and whether periostin is useful for diagnosis, prognosis, and monitoring in this patient group (PROSPERO registration number: CRD42024623501).

Inflammation is a complex and necessary mechanism of an organ's response to biological, chemical and/or physical stimuli. In recent years, investigations on natural compounds with therapeutic actions for the treatment of different diseases have increased. Among these compounds, bromelain is highlighted, as a cysteine protease isolated from the Ananas comosus (pineapple) stem. This review aimed to evaluate the anti-inflammatory activity of bromelain, as well as its pathways on inflammatory mediators, through a systematic review with in vitro studies on different cell lines. The search was performed in PubMed, Science Direct, Scopus, Cochrane Library and Web of Science databases. Bromelain reduced IL-1β, IL-6 and TNF-α secretion when immune cells were already stimulated in an overproduction condition by proinflammatory cytokines, generating a modulation in the inflammatory response through prostaglandins reduction and activation of a cascade reactions that trigger neutrophils and macrophages, in addition to accelerating the healing process.

Diabetic peripheral neuropathy (DPN) is a debilitating complication of diabetes mellitus, characterized by progressive nerve damage driven by chronic hyperglycemia and systemic inflammation. The pathophysiology of DPN is significantly influenced by pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α. These cytokines promote oxidative stress, vascular dysfunction, and neuronal degeneration by activating important signaling pathways including NF-κB and MAPK. While IL-6 promotes a pro-inflammatory microenvironment, increasing neuronal damage and neuropathic pain, TNF-α and IL-1β worsen Schwann cell failure by compromising axonal support and causing demyelination. Immune cell infiltration and TLR activation increase the inflammatory cascade in DPN, resulting in a persistent neuroinflammatory state that sustains peripheral nerve injury. The main characteristics of DPN are axonal degeneration, decreased neurotrophic support, and Schwann cell dysfunction, which weaken nerve transmission and increase susceptibility to damage. Advanced glycation end-products, TNF-α, and CXCL10 are examples of biomarkers that may be used for early diagnosis and disease progression monitoring. Additionally, crucial molecular targets have been found using proteomic and transcriptome techniques, enabling precision medicine for the treatment of DPN. This review emphasizes the importance of cytokine signaling in the pathogenesis of DPN and how cytokine-targeted treatments might reduce inflammation, restore nerve function, and improve clinical outcomes for diabetic patients.

High basophil count levels are associated with an increased risk of gestational diabetes mellitus (GDM). We used two-sample Mendelian randomisation (MR) to explore a potential causal relationship. It also aims to offer genetic evidence supporting the link between basophil count and the development of gestational diabetes mellitus while addressing the potential issues of confounding and reverse causality commonly encountered in observational studies.

We utilized publically accessible summary information obtained from genome-wide association studies (GWAS) for conducting a two-sample Mendelian randomization (TSMR) study. The major analysis method employed was inverse variance weighted (IVW), whereas the other four methods, namely weighted median method, MR-Egger regression, simple model and weighted model, were used as supplemental analyses. We also investigated the relationship between GDM and basophil count in the opposite direction using directional validation of MR analysis. Furthermore, the R package "ClusterProfiler" to conduct an analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) terms was used. Additionally, with the help of the STRING database, we have constructed a network of protein-protein interactions (PPIs).

The Inverse Variance Weighted (IVW) method revealed a significant causal association between basophil count and gestational diabetes mellitus (OR, 0.84; 95% CI; 0.74-0.96; P, 0.01). A sensitivity analysis was performed to assess the reliability of the results, indicating no indication of pleiotropy or heterogeneity, hence strengthening the validity of the findings. The reverse causation of GDM predisposition on basophil counts was not supported by the results of the directional validation of the MR analysis.

The results of this study showed a causal relationship between high basophil counts and increased risk of GDM but did not support a causal relationship between genetic susceptibility to GDM and basophil counts.

Dipteryx alata Vogel., popularly known as "baru", is a native species of Brazilian cerrado used by "Ribeirinhos" in the North Araguaia microregion. In the traditional medicine, maceration of barks or leaves infusion are used to treat back and muscle pain, osteoporosis and rheumatism. However, few studies have demonstrated the pharmacological effects of this species.

The goal of this study was to perform phytochemicals studies of lyophilized infusion of D. alata leaves (LI-DA), as well as obtaining ethyl acetate fraction (EAF-DA) and hydromethanolic fraction (HMF-DA), and isolated flavonoids. The antioxidant of LI-DA, EAF-DA and HMF-DA, anti-inflammatory effects of LI-DA and quercetin-3-O-β-glucoside-7-O-α-rhamnoside (DA-1) and quercetin-7-O-α-rhamnoside (DA-2) were performed while in silico tests were used for absorption, distribution, metabolism, excretion and toxicity predictions of DA-1 and DA-2.

LI-DA, EAF-DA and HMF-DA were evaluated in antioxidant assays (2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid - ABTS; 2,2-diphenyl-1-picrylhydrazyl - DPPH; hydrogen peroxide - H2O2; reducing power and oxidation of β-carotene). The DA-1 and DA-2 were isolated from EAF-DA using chromatographic methods and characterized by Nuclear Magnetic Resonance (NMR) spectrometer. The Programs ProTox 3.0 and ADMETlab 2.0 were used for the prediction studies of DA-1 and DA-2. Mice received a single dose of LI-DA (3, 30, and 100 mg/kg), DA-1 (3 mg/kg) and DA-2 (3 mg/kg) and were subjected to inflammation induced by Complete Freund's Adjuvant (CFA) and in the zymosan-induced articular inflammation model.

DA-1 and DA-2 have been identified for the first time in the leaves of D. alata. LI-DA, EAF-DA and HMF-DA demonstrated a high level of antioxidant activity as measured by ABTS (IC50 ≤ 5.62 μg/mL) and DPPH (IC50 ≤ 11.45 μg/mL). Oral administration of LI-DA (3, 30 and 100 mg/kg), DA-1 (3 mg/kg) and DA-2 (3 mg/kg) showed significantly reduced edema, cold and mechanical allodynia in the CFA-induced inflammation model (24 h). LI-DA (3, 30, and 100 mg/kg) and DA-1 (3 mg/kg) reduced leukocytes migration into the joint cavity, mechanical allodynia, edema and NO production in mice (24 h) in the zymosan-induced articular inflammation model. Additionally, DA-2 (3 mg/kg) reduced leukocyte migration and LI-DA (30 mg/kg) reduced protein exudation (24 h) in zymosan model. DA-1 and DA-2 showed good oral bioavailability and low toxicity predicted by the ProTox model.

This is the first chemical and biological study performed of D. alata infusion and two quercetin glycoside derivatives. The results indicated promising potential for the treatment of inflammation, pain, and rheumatism, supporting the traditional use of the infusion obtained from the leaves of D. alata.

Neuronal guidance proteins (NGPs) have been demonstrated to guide the elongation of neuronal axonal growth cones in the developing central nervous system. Non-neuronal functions of NGPs have also been described, especially in relation to atherosclerosis.

Netrin-1 and repulsive guidance molecule a (RGMa) are NGPs that have been shown to regulate endothelial cell adhesion and angiogenesis, macrophage migration and apoptosis, smooth muscle cells (SMCs) phenotypic dedifferentiation and mobility, chemokine activities, and inflammatory responses during atherosclerosis initiation and progression.

However, mechanistic studies have generated controversy about the specific role of Netrin-1 in atherosclerosis due to the diversity of its structure, receptors and cell sources, and the actions of RGMa in atherosclerosis have not been reported in previous reviews. Therefore, the current work reviews the evidence for roles of Netrin-1 and RGMa in the initiation and progression of atherosclerosis and discusses potential therapeutic targets in the future.

Normal brain aging is associated with dopamine decline, which has been linked to age-related cognitive decline. Factors underlying individual differences in dopamine integrity at older ages remain, however, unclear. Here we aimed at investigating: (i) whether inflammation is associated with levels and 5-year changes of in vivo dopamine D2-receptor (DRD2) availability, (ii) if DRD2-inflammation associations differ between men and women, and (iii) whether inflammation and cerebral small-vessel disease (white-matter lesions) serve as two independent predictors of DRD2 availability.

Analyses were performed in a sample of healthy adults > 60 years assessed at two measurement occasions separated by 5 years. At both occasions, DRD2 availability was estimated by 11C-raclopride PET, and white-matter lesions by MRI. Inflammation was assessed by two C-reactive protein-associated DNA methylation scores at study baseline.

Individuals with higher DNA methylation scores at baseline showed reduced striatal DRD2 availability. An interaction was found between DNA methylation scores and sex in relation to striatal DRD2 availability, such that associations were found in men but not in women. DNA methylation scores at study entrance were not significantly associated with 5-year striatal DRD2 decline rates. No significant association was found between DNA methylation scores and white-matter lesions, but higher scores as well as higher lesion burden were independently associated with reduced striatal DRD2 availability in men.

These findings suggest negative associations between one proxy of inflammation and DRD2 availability in older adults, selectively for men who had higher DNA methylation scores. Future studies should investigate other inflammatory markers in relation to dopamine integrity.

Background/Objectives: Inflammation is a vital response of the immune system, frequently linked to the development and progression of numerous chronic and autoimmune diseases. Targeting inflammation represents an attractive strategy to prevent and treat these pathologies. In this context, many pathways, including pro-inflammatory cytokines secretion, NFκB activation, reactive oxygen species (ROS) production, inflammasome activation and arachidonic acid metabolism could be highlighted and addressed. Several plant materials have traditionally been used as effective and non-harmful anti-inflammatory agents. However, well-established scientific evidence is lacking, and their mechanisms of action remain unclear. The current article compares the effects of seven plant extracts, including Quercus robur L. (Oak), Plantago lanceolata L. (narrowleaf plantain), Plantago major L. (broadleaf plantain), Helichrysum stoechas L. (immortelle or helichrysum), Leontopodium nivale alpinum Cass. (edelweiss), Medicago sativa L. (alfafa) and Capsella bursa-pastoris Moench (shepherd's purse) on different inflammatory pathways. Results: All of the plant extracts significantly affected ROS production, but their action on cytokine production was more variable. As the Quercus robur extract showed the highest efficacy in our models, it was subsequently assessed on several inflammatory signaling pathways. Quercus robur significantly decreased the secretion of IFNγ, IL-17a, IL-12, IL-2, IL-1β and IL-23 in stimulated human leucocytes, and the expression of TNFα, IL-6, IL-8, IL-1β and CXCL10 in M1-like macrophages. Additionally, a significant reduction in PGE2 secretion, COX2, NLRP3, caspase1 and STAT3 expression and NFκB p65 phosphorylation was observed. Conclusions: Our results clearly indicate that Quercus robur has a potent anti-inflammatory effect, making it a promising candidate for both the treatment and prevention of inflammation and related diseases, thereby promoting overall well-being.

Flavones are natural compounds that are broadly distributed in our diet. Their unique properties provide the possibility to control the immune system and the process of inflammation. A high intake of flavonoids, including flavones, may offer protection against reactive oxygen species, inflammation, and chronic diseases. In this research, we evaluated the anti-inflammatory effect of five methylflavones, 2'-methylflavone (5C), 3'-methylflavone (6C), 4'-methylflavone (7C), 6-methylflavone (8C), and 6-methyl-8-nitroflavone (12C), in lipopolysaccharide (LPS) stimulated RAW 264.7 cells (murine macrophage cell line). We estimated the nitrite concentration and detected reactive oxygen species using the chemiluminescence method. Moreover, we measured the production of pro-inflammatory cytokines using the Bio-Plex Magnetic Luminex Assay. As a result of our findings, we have established that some of the methyl derivatives of flavone inhibit nitric oxide (NO) production and chemiluminescence generated by LPS-stimulated macrophages, but they also have an influence on pro-inflammatory cytokines production. This study showed that 2'-methylflavone (5C) and 3'-methylflavone (6C) possess the strongest anti-inflammatory activity among all tested derivatives of flavone. In conclusion, our study demonstrated that methylflavones may be potentially valuable compounds for the alleviation of inflammatory reactions.

Seaweeds are natural sources of sulfated polysaccharides (SPs), biopolymers with remarkable pharmacological properties, including biological actions capable of attenuating components of the inflammatory process such as edema, cytokines, cell migration and pain. Our results confirm that SPs obtained from Gracilaria domingensis (SP-GD) are agarans, primarily composed of residues of β-d-galactopyranose 6-sulfate and 3,6-anhydro-α-l-galactopyranose. Specifically, SP-GD at a dose of 10 mg/kg was effective in significantly reducing paw edema induced by carrageenan or histamine, serotonin, bradykinin, 48/80 and prostaglandin E2. SP-GD (10 mg/kg) was also able to reduce neutrophil migration and the activity of the myeloperoxidase enzyme in carrageenan-induced peritonitis, as well as conserve glutathione concentration and reduce malondialdehyde levels in the animals' peritoneal fluid. Furthermore, it showed antinociceptive action in the abdominal writhing test induced by acetic acid and in the paw licking test induced by formalin. Thus, the results obtained allow us to infer that SPs extracted from G. domingensis at a dose of 10 mg/kg have anti-inflammatory effects by reducing neutrophil migration and modulating the activity of vasoactive mediators and antinociceptive effects by acting, at least in part, through a peripheral mechanism dependent on the negative modulation of inflammatory mediators.

Interleukin-4 (IL-4), which is traditionally associated with inflammation, has emerged as a key player in tissue regeneration. Produced primarily by T-helper 2 (Th2) and other immune cells, IL-4 activates endogenous lymphocytes and promotes M2 macrophage polarization, both of which are crucial for tissue repair. Moreover, IL-4 stimulates the proliferation and differentiation of various cell types, contributing to efficient tissue regeneration, and shows promise for promoting tissue regeneration after injury. This review explores the multifaceted roles of IL-4 in tissue repair, summarizing its mechanisms and potential for clinical application. This review delves into the multifaceted functions of IL-4, including its immunomodulatory effects, its involvement in tissue regeneration, and its potential therapeutic applications. We discuss the mechanisms underlying IL-4-induced M2 macrophage polarization, a crucial process for tissue repair. Additionally, we explore innovative strategies for delivering IL-4, including gene therapy, protein-based therapies, and cell-based therapies. By leveraging the regenerative properties of IL-4, we can potentially develop novel therapies for various diseases, including chronic inflammatory disorders, autoimmune diseases, and organ injuries. While early research has shown promise for the application of IL-4 in regenerative medicine, further studies are needed to fully elucidate its therapeutic potential and optimize its use.

Skin wounds can drive global impacts, socially and economically, in parallel with their elevated incidence rate. Therefore, utilizing the dual-activity of Brassica Oleracea (Red Cabbage) extract, of being pH-sensitive and biologically active in designing novel, therapeutic, and pH-sensitive wound dressings with an easily stripped-off feature, is critical. Wound dressings were designed using two separate hydrogels based on chitosan (CS) and hydroxyethylcellulose (HEC), each loaded with RCE. The pH sensitivity of prepared bandages exhibited a noticeable visual change in color during wound treatment. Wound closure has reached 99.69 % for CS/RCE dressings. Results showed that RCE had raised the hydroxyproline and collagen content in the healed skin. Histopathological investigation proves that skin returned to its regular thickness within 10 days of treatment. RCE showed marked improvement in the healing quality by acting as an antioxidant, anti-inflammatory, and antimicrobial agent. Therefore, dual-function dressings are potential candidates to sense and cure skin wounds.

The objective of this study was to evaluate the utility of inflammation-based prognostic scores (IBPS) in predicting ORN among patients undergoing superselective intra-arterial chemoradiotherapy (SSIACRT). This retrospective cohort study examined the medical records of 54 patients with advanced oral cancer (stage 3 or 4) treated with SSIACRT. The predictor variable was IBPS. The main outcome variable was onset of ORN. Covariates comprised sex, median age, tooth status, tumor size, and pretreatment tooth extraction with professional oral care (pretreatment tooth extraction). For each factor, cumulative incidence and univariate and multivariate analyses of ORN incidence were performed. The cumulative incidence of ORN in patients with pre-treatment lymphocyte-to-monocyte ratio (LMR < 4.95vs LMR ≥4.95, P = 0.01) and pretreatment tooth extraction (no vs. yes, P = 0.03) was significantly different. Univariate and multivariate analyses identified pre-treatment LMR cutoff values < 4.95 and pre-treatment tooth extraction as significantly associated with the development of ORN. Pretreatment tooth extraction reduced the incidence of ORN in low LMR group (P = 0.04). LMR is a useful biomarker to predict ORN in SSIACRT. Pretreatment tooth extraction was a useful treatment to prevent ORN. Pretreatment extraction with LMR may be important for the prevention of ORN in SSIACRT.

Male fertility results from a complex interplay of physiological, environmental, and genetic factors. It is conditioned by the properly developed anatomy of the reproductive system, hormonal regulation balance, and the interplay between different cell populations that sustain an appropriate and functional environment in the testes. Unfortunately, the mechanisms sustaining male fertility are not flawless and their perturbation can lead to infertility. Inflammation is one of the factors that contribute to male infertility. In the testes, it can be brought on by varicocele, obesity, gonadal infections, leukocytospermia, physical obstructions or traumas, and consumption of toxic substances. As a result of prolonged or untreated inflammation, the testicular resident cells that sustain spermatogenesis can suffer DNA damage, lipid and protein oxidation, and mitochondrial dysfunction consequently leading to loss of function in affected Sertoli cells (SCs) and Leydig cells (LCs), and the formation of morphologically abnormal dysfunctional sperm cells that lay in the basis of male infertility and subfertility. This is due mainly to the production and secretion of pro-inflammatory mediators, including cytokines, chemokines, and reactive oxygen species (ROS) by local immune cells (macrophages, lymphocytes T, mast cells) and tissue-specific cells [SCs, LCs, peritubular myoid cells (PMCs) and germ cells (GCs)]. Depending on the location, duration, and intensity of inflammation, these mediators can exert their toxic effect on different elements of the testes. In this review, we discuss the most prevalent inflammatory factors that negatively affect male fertility and describe the different ways inflammation can impair male reproductive function.

One of the important markers affecting aging processes is the increase in inflammatory markers. Many chronic diseases are associated with inflammation and chronic inflammation increases with aging. Inflammation can change with dietary components. Foods, compounds and nutrients that have anti-inflammatory or proinflammatory properties attract attention. According to the Dietary Inflammatory Index, positive scores are obtained if the nutrient has a proinflammatory effect on cytokines, and negative scores are obtained if it has an anti-inflammatory effect.

A higher proinflammatory diet is associated with cardiometabolic diseases, neurodegenerative disease, cancers and musculoskeletal health and related mortality. In this study, its relationship with type 2 diabetes mellitus, obesity, metabolic syndrome, musculoskeletal diseases, dementia, depression and cancer, which are more common in older adults and known to be associated with inflammation, was examined. Although studies involving under 65 years old are more prevalent, research involving older adults and Dietary Inflammatory Index (DII) is more limited. It is known that chronic inflammation increases with aging. Diet is one of the factors affecting inflammation. In the light of these investigations, the topics of anti-inflammatory nutrition and DII for the treatment of inflammation-related diseases in older adults are strong and open to development topics of discussion. Despite the significant interest in the potential positive effects of anti-inflammatory nutrition on diseases, contributing to clearer evidence of its protective effects on health necessitates further randomized controlled trials, in vivo, in vitro, cell, animal, human and case-control studies for better risk assessment.

Hesperidin is a kind of flavonoids, which has the biological activities of antioxidation, anti-inflammation, antibacterial, anti-virus, anti-allergy, anti-cancer, heart protection and neuroprotection. More and more studies have begun to pay attention to the therapeutic prospect of hesperidin in central nervous system (CNS) diseases. This paper describes its current role in the treatment of central nervous system diseases, especially stroke, and discusses its bioavailability, so as to provide a theoretical basis for the clinical application of hesperidin.

Exosomes have garnered attention as a potential cell-free therapy for inflammatory diseases due to their immunomodulatory and anti-inflammatory properties. Exosome-like nanoparticles isolated from Arbutus unedo were characterized and analyzed for their anti-inflammatory potential. The results revealed that the isolated exosomes exhibited a spheroid morphology, with an approximate modal size of 190 nm. Exposure to these exosomes significantly reduced the mRNA expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), the glycoprotein CD80, the transcription factor STAT1, and pro-inflammatory cytokine genes like IL-1b and IL-6, in lipopolysaccharide (LPS)-induced protein RAW264.7 cells. In addition, exosomes reduced the LPS-induced protein levels of PSTAT1 and STAT1, IRF1 and RelB, which are key transcription factors in the control of proinflammatory gene expression. LC-MS analysis identified the presence of carotenoids, mainly β-carotene, with known anti-inflammatory activity, related to its ROS-scavenging activity, suggesting its potential contribution to the anti-inflammatory activity of the exosomes isolated from A. unedo fruits.

The Oxidative Balance Score (OBS), which reflects overall oxidation through diet and lifestyle, has been linked to sleep, but few studies have clarified this relationship. We investigated the association between OBS and sleep duration, and whether oxidative stress (OS) and inflammation mediate the underlying mechanisms.

Data were obtained from the National Health and Nutrition Examination Survey spanning the years 2007 to 2018. Multivariable logistic regression analyses were used to evaluate the association between OBS and the risk of sleep duration. Mediation analyses were conducted to investigate the role of OS and inflammatory markers.

A significant negative association was found between OBS and sleep duration (p < 0.01). Meanwhile, compared to participants in OBS tertile 1, the ORs (95% CIs) of incident short sleep duration were 0.78 (0.72-0.86) and 0.72 (0.67-0.79) (both p < 0.01) for OBS tertile 2 and 3, respectively. And the ORs (95% CIs) of incident long sleep duration were 0.83 (0.73, 0.95) and 0.66 (0.57, 0.75) (both p < 0.01) for OBS tertiles 2 and 3 after adjustment for multivariate variables. A linear relationship between OBS and short/long sleep duration (p for non-linearity = 0.69/0.94, both p < 0.01) were revealed. Mediation analysis showed absolute neutrophil count, serum total bilirubin mediated the association between OBS and short/long sleep duration with 5.72, 13.41% proportion of mediation, respectively (both p < 0.001).

OBS is negatively associated with sleep duration. OS and inflammatory biomarkers mediate the relationship.

Methotrexate (MTX) is a folic acid reductase inhibitor that manages various malignancies as well as immune-mediated inflammatory chronic diseases. Despite being frequently prescribed, MTX's severe multiple toxicities can occasionally limit its therapeutic potential. Intestinal toxicity is a severe adverse effect associated with the administration of MTX, and patients are significantly burdened by MTX-provoked intestinal mucositis. However, the mechanism of such intestinal toxicity is not entirely understood, mechanistic studies demonstrated oxidative stress and inflammatory reactions as key factors that lead to the development of MTX-induced intestinal injury. Besides, MTX causes intestinal cells to express pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which activate nuclear factor-kappa B (NF-κB). This is followed by the activation of the Janus kinase/signal transducer and activator of the transcription3 (JAK/STAT3) signaling pathway. Moreover, because of its dual anti-inflammatory and antioxidative properties, nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) has been considered a critical signaling pathway that counteracts oxidative stress in MTX-induced intestinal injury. Several agents have potential protective effects in counteracting MTX-provoked intestinal injury such as omega-3 polyunsaturated fatty acids, taurine, umbelliferone, vinpocetine, perindopril, rutin, hesperidin, lycopene, quercetin, apocynin, lactobacillus, berberine, zinc, and nifuroxazide. This review aims to summarize the potential redox molecular mechanisms of MTX-induced intestinal injury and how they can be alleviated. In conclusion, studying these molecular pathways might open the way for early alleviation of the intestinal damage and the development of various agent plans to attenuate MTX-mediated intestinal injury.

Inflammation-driven diseases encompass a wide array of pathological conditions characterised by immune system dysregulation leading to tissue damage and dysfunction. Among the myriad of mediators involved in the regulation of inflammation, histamine has emerged as a key modulatory player. Histamine elicits its actions through four rhodopsin-like G-protein-coupled receptors (GPCRs), named chronologically in order of discovery as histamine H1, H2, H3 and H4 receptors (H1-4R). The relatively low affinity H1R and H2R play pivotal roles in mediating allergic inflammation and gastric acid secretion, respectively, whereas the high affinity H3R and H4R are primarily linked to neurotransmission and immunomodulation, respectively. Importantly, however, besides the H4R, both H1R and H2R are also crucial in driving immune responses, the H2R tending to promote yet ill-defined and unexploited suppressive, protective and/or resolving processes. The modulatory action of histamine via its receptors on inflammatory cells is described in detail. The potential therapeutic value of the most recently discovered H4R in inflammatory disorders is illustrated via a selection of preclinical models. The clinical trials with antagonists of this receptor are discussed and possible reasons for their lack of success described.

Background: Metabolic inflammation (MI), long COVID (LC) and systemic lupus erythematosus (SLE) share some metabolic common manifestations and inflammatory pathophysiological similarities. Health-related quality of life (HRQoL) and metabolic age are indicators of health status. The "METAINFLAMMATION-CM Y2020/BIO-6600" project, a prospective controlled study, aimed to identify differential diagnostic tools and clinical features among three inflammatory conditions by comparing obesity status (low BMI vs. high BMI). Methods: A total of 272 adults of both Caucasian and Hispanic descent, diagnosed with MI, LC or SLE, and a range of BMI, were recruited. Clinical and phenotypic traits were measured to analyze body composition, metabolic and inflammatory markers, HRQoL data, metabolic age and lifestyle habits using a 3 × 2 (disease × BMI) factorial design. Results: Some inflammatory related variables, such as fibrinogen, RDW (red cell blood distribution width), ESR (erythrocyte sedimentation rate) and NLR (neutrophil/lymphocyte ratio), showed effect modifications depending on the BMI and disease type. In relation to HRQoL, the Physical Component Summary (PCS12) showed no relevant changes, while the Mental Component Summary (MCS12) showed a significant effect modification according to the disease type and BMI (p < 0.05). Furthermore, a significant interaction was identified between the disease type and BMI in relation to metabolic age (p = 0.02). Conclusions: Assessing the impact of BMI on these three inflammatory diseases may help to prevent clinical complications and to design personalized treatments, especially for patients with SLE, who have a worse prognosis with an increased BMI compared to the other two inflammatory diseases.

The processes of apoptosis and inflammatory responses, which are defensive strategies used by cells to confront external substances, can give rise to diverse diseases when prolonged or disrupted, such as cancer, Alzheimer's disease, and Parkinson's disease. Here we engineered a live-cell imaging fluorescent probe for nitric oxide (NO) based on naphthalimide and o-phenylenediamine, enabling the sensitive detection of NO in cancer cells and thereby live-monitoring of the doxorubicin-induced apoptosis and lipopolysaccharide-triggered inflammation reactions. Importantly, we found that the level of released NO can sensitively indicate the early stages of both cellular inflammatory responses and apoptotic processes. This suggested that cellular NO in fact behaves as a new class of signaling molecule for inflammatory responses and apoptosis processes, providing a potent tool for live-monitoring cellular physiological reactions.

Chronic inflammatory diseases pose a substantial health challenge globally, significantly contributing to morbidity and mortality. Addressing this issue requires the use of effective anti-inflammatory strategies with fewer side effects than those provoked by currently used drugs. In this study, a range of phytochemicals (phenolic di-caffeoylquinic acid (Di-CQA), flavonoid cyanidin-3,5-diglucoside (Cy3,5DiG), aromatic isothiocyanate sinalbin (SNB) and aliphatic isothiocyanate sulforaphane (SFN)) sourced from vegetables and fruits underwent assessment for their potential anti-inflammatory activity. An in vitro model of human macrophage-like cells treated with a low dose of LPS to obtain a low degree of inflammation that emulates a chronic inflammation scenario revealed promising results. Cell viability and production of the key pro-inflammatory cytokines were assessed in the presence of various phytochemicals. The compounds Di-CQA and Cy-3,5-DiG, within low physiologically relevant doses, demonstrated notable anti-inflammatory effects by significantly reducing the production of key pro-inflammatory cytokines TNF-α and IL-6 without affecting cell viability. These findings underscore the potential of plant-derived bioactive compounds as valuable contributors to the prevention or treatment of chronic inflammatory diseases. These results suggest that these compounds, whether used individually or as part of natural mixtures, hold promise for their inclusion in nutritional interventions designed to mitigate inflammation in associated pathologies.

Coumarin, a naturally occurring compound found in various plants, has a rich history of use in traditional medicine. Recent research has highlighted its anti-inflammatory properties, positioning it as a promising candidate for treating inflammatory disorders such as rheumatoid arthritis, asthma, and inflammatory bowel disease. This narrative review aims to comprehensively summarize the current knowledge regarding coumarin's pharmacological effects in alleviating inflammatory conditions by analyzing preclinical and clinical studies. The review focuses on elucidating the mechanisms through which coumarin exerts its anti-inflammatory effects, including its antioxidant activity, inhibiting pro-inflammatory cytokine production, and modulation of immune cell functions. Additionally, the paper addresses potential limitations of using coumarin, such as concerns about toxicity at high doses or with prolonged use. Before widespread clinical application, further investigation is needed to fully understand coumarin's potential benefits and risks.

Previous studies have shown that stroke patients exhibit greater neuroimaging-derived biological "brain age" than control subjects. This difference, known as the brain age gap (BAG), is calculated by comparing the chronological age with predicted brain age and is used as an indicator of brain health and aging. However, whether stroke accelerates the process of brain aging in patients with small-volume infarcts has not been established. By utilizing longitudinal data, we aimed to investigate whether small-volume infarctions can significantly increase the BAG, indicating accelerated brain aging.

A total of 123 stroke patients presenting with small-volume infarcts were included in this retrospective study. The brain age model was trained via established protocols within the field of machine learning and the structural features of the brain from our previous study. We used t-tests and regression analyses to assess longitudinal brain age changes after stroke and the associations between brain age, acute stroke severity, and poststroke outcome factors.

Significant brain aging occurred between the initial and 6-month follow-ups, with a mean increase in brain age of 1.04 years (t = 3.066, p < 0.05). Patients under 50 years of age experienced less aging after stroke than those over 50 years of age (p = 0.245). Additionally, patients with a National Institute of Health Stroke Scale score >3 at admission presented more pronounced adverse effects on brain aging, even after adjusting for confounders such as chronological age, sex, and total intracranial volume (F 1,117 = 7.339, p = 0.008, η 2 = 0.059). There were significant differences in the proportional brain age difference at 6 months among the different functional outcome groups defined by the Barthel Index (F 2,118 = 4.637, p = 0.012, η 2 = 0.073).

Stroke accelerates the brain aging process, even in patients with relatively small-volume infarcts. This phenomenon is particularly accentuated in elderly patients, and both stroke severity and poststroke functional outcomes are closely associated with accelerated brain aging. Further studies are needed to explore the mechanisms underlying the accelerated brain aging observed in stroke patients, with a particular focus on the structural alterations and plasticity of the brain following minor strokes.

Inflammation serves as an intricate defense mechanism for tissue repair. However, overactivation of TLR4-mediated inflammation by lipopolysaccharide (LPS) can lead to detrimental outcomes such as sepsis, acute lung injury, and chronic inflammation, often associated with cancer and autoimmune diseases. This study delves into the anti-inflammatory properties of "Aspergillus unguis isolate SP51-EGY" on LPS-stimulated RAW 264.7 macrophages. Through real-time qPCR, we assessed the expression levels of pivotal inflammatory genes, including iNOS, COX-2, TNF-α, and IL-6. Remarkably, our fungal extracts significantly diminished NO production and showed noteworthy reductions in the mRNA expression levels of the aforementioned genes. Furthermore, while Nrf2 is typically associated with modulating inflammatory responses, our findings indicate that the anti-inflammatory effects of our extracts are not Nrf2-dependent. Moreover, the chemical diversity of the potent extract (B Sh F) was elucidated using Q-TOF LC-HRMS, identifying 54 compounds, some of which played vital roles in suppressing inflammation. Most notably, compounds like granisetron, fenofibrate, and umbelliprenin were found to downregulate TNF-α, IL-1β, and IL-6 through the NF-κB signaling pathway. In conclusion, "Aspergillus unguis isolate SP51-EGY", isolated from the Red Sea, Egypt, has been unveiled as a promising TLR4 inhibitor with significant anti-inflammatory potentials, presenting novel insights for their potential therapeutic use in inflammation.

Erythrocyte Sedimentation Rate (ESR) is an easy test used to diagnose and monitor inflammatory and infectious diseases. The aim of this study was the evaluation of the performance of three ESR automated analyzers, VES-MATIC 5, CUBE 30 TOUCH, and MINI-CUBE, involving four Italian polyclinics in Rome, Siena, Como, and Arezzo, as well as inter-site variability assessment to detect possible device-dependent and operator-dependent influences.

Accuracy analysis was carried out by analyzing the same samples with all three instruments and comparing them with the Westergren method. Precision was assessed with quality control material through intra-run and inter-run precision. Repeatability was estimated by reanalyzing fresh blood samples belonging to three ESR ranges (low, intermediate, and high) six times.

The results showed a strong correlation (Spearman coefficients R2) between the manual method and VES-MATIC 5 (0.978), CUBE 30 TOUCH (0.981), and MINI-CUBE (0.974). The accuracy of all clinics was excellent, with coefficients of variation (CVs) of less than 10% for all instruments. Repeatability confirmed an excellent level for all ESR ranges, with CVs below 10%.

The study proved that all three automated instruments offer optimal performance for accuracy and precision and are suitable for both large and small facilities without influences of the laboratory environment.

Dental pulp inflammation, often initiated by Gram-negative microorganisms and lipopolysaccharides (LPS), can lead to pulpitis and, subsequently, dental pulp necrosis, compromising tooth structure and increasing susceptibility to fracture. Asiatic acid, derived from Centella asiatica, has demonstrated pharmacological properties, including anti-inflammatory and antioxidant effects, making it a potential candidate for mitigating LPS-induced pulp inflammation. This in vivo study aims to investigate the impact of Asiatic acid on the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in Rattus norvegicus with LPS-induced pulp inflammation.

This quasi-laboratory experimental in vivo study employed a post-test-only control group design to investigate the effects of Asiatic acid on LPS-induced pulp inflammation in Wistar rats. Thirty rats were randomly divided into six groups subjected to various interventions. LPS was administered to all groups for 6 h except the standard control group (CG, n = 5). The negative control group (NCG, n = 5) received only glass ionomer cement. The positive control group (PCG, n = 5) received Eugenol with glass ionomer cement. Intervention groups 1, 2, and 3 (IG1, IG2, IG3; n = 5 each) received Asiatic acid at concentrations of 0.5%, 1%, and 2%, respectively, with glass ionomer cement. Dental pulp inflammation was confirmed through immunological (tumor necrosis factor alpha (TNF-α) levels), histopathological (inflammatory parameters), and physiological (pain assessment using the rat grimace scale) analyses. Additionally, Nrf2 levels were examined using enzyme-linked immunosorbent assay (ELISA).

Asiatic acid administration significantly influenced Nrf2 levels in rats with LPS-induced pulp inflammation. Nrf2 levels were significantly higher in groups treated with 0.5% (IG1) (8.810 ± 1.092 ng/mL; p = 0.047), 1.0% (IG2) (9.132 ± 1.285 ng/mL; p = 0.020), and 2.0% (IG3) (11.972 ± 1.888 ng/mL; p = 0.000) Asiatic acid compared to NCG (7.146 ± 0.706). Notably, Nrf2 levels were also significantly higher in the 2.0% Asiatic acid group (IG3) compared to the PCG treated with Eugenol (8.846 ± 0.888 ng/mL; p = 0.001), as well as IG1 (p = 0.001) and IG2 (p = 0.002). However, no significant difference was observed between administering 0.5% Asiatic acid (IG1), 1.0% Asiatic acid (IG2), and Eugenol (PCG).

This research showed that Asiatic acid significantly impacted the Nrf2 levels in rats with LPS-induced pulp inflammation. This suggests that it has the potential to be used as a therapeutic agent for reducing dental pulp inflammation. These findings support the need to further explore Asiatic acid as a promising intervention for maintaining dental pulp health.

This study investigated the anti-inflammatory effect of hydrophilic and lipophilic extracts from juçara fruits (Euterpe edulis Martius) through measurement of nitric oxide (NOx) and cytokines (IL-12p70, TNF-α, INF-γ, MCP-1, IL-6, and IL-10). J774 macrophages were stimulated with lipopolysaccharides (1 µg/mL) and treated with various concentrations (1-100 µg/mL) of juçara fruits extracts from crude extracts, and hexane, dichloromethane, ethyl acetate, and butanol fractions. Potential relationships between the phenolic composition of the extracts determined by LC-ESI-MS/MS and their anti-inflammatory capacity were also evaluated. Hexane and dichloromethane fractions inhibited NOx and IL-12p70 while increased IL-10. Hexane fractions also decreased IL-6 and IFN-γ production. Hexane and dichloromethane fractions showed a higher number of phenolic compounds (32 and 34, respectively) than the other extracts tested and were also the only ones that presented benzoic acid and pinocembrin. These results suggest juçara fruits compounds as potential anti-inflammatory agents, especially those of a more apolar nature.

Inflammation has been postulated as a mediating factor in the development of Alzheimer's disease (AD) pathology. We investigated candidate inflammatory markers related to conversion to AD among patients with depression.

A longitudinal study was conducted with older women with depression who were at least 55 years of age, with a mean follow-up period of 5.73 years. At baseline, 9 inflammatory cytokines were measured using the immunoreactivity method. During follow-up, patients with depression who complained of cognitive impairment were evaluated and diagnosed with AD conversion. Association of the cytokines with conversion to AD was analyzed using multivariable Cox proportional hazards regression with adjusting covariates. For clinical applicability, the optimal cutoff value was determined using the minimum p value approach for the conversion to AD and was used to plot an AD-free survival curve.

Among 132 participants, 34 patients with depression (25.76%) developed AD during their follow-up period. Higher levels of interleukin (IL) 1β at baseline (hazard ratio = 3.30 [95% CI, 1.11-9.78], p = .031) and lower levels of IL-10 (p < .001) were significantly associated with an increased risk of progression to AD. The survival curve plotted by the cutoff value of ≥0.25 pg/mL for IL-1β and ≤0.15 pg/mL for IL-10 suggested adjusted hazard ratios of 8.96 (95% CI, 3.48-23.09; p < .001) for IL-1β and 10.99 (p < .001) for IL-10, respectively.

This study demonstrated that IL-1β and IL-10 were associated with conversion to AD among patients with late-life depression, suggesting their potential as predictive markers of the transition to AD from depression.

This study employed a ligand-based pharmacophoric approach to design and synthesize 33 novel semisynthetic labdane-appended triazolyl isatins to discover potential anti-inflammatory agents. The anti-inflammatory efficacy of the derivatives was evaluated by their ability to inhibit the production of NO, TNF-α, and IL-6, in lipopolysaccharide-induced RAW264.7 macrophages. The initial screening revealed that compound 7a ((1-(2-(2,3-dioxoindolin-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl (E)-3-formyl-5-((1S,4aS,8aS)-5,5,8a-trimethyl-2-methylenedecahydronaphthalen-1-yl)pent-3-enoate) exhibited an anti-inflammatory effect (NO inhibition, IC50 = 3.13 μΜ), surpassing both the positive control indomethacin (NO inhibition, IC50 = 7.31 μΜ) and the parent compound labdane dialdehyde. Notably, 7a reduced the levels of pro-inflammatory cytokines TNF-α and IL-6 while increasing the levels of the anti-inflammatory cytokine IL-10. Mechanistic studies revealed that 7a downregulated the expression of COX-2 and iNOS by inhibiting the NF-κB signaling pathway. In silico molecular modeling studies on NF-κB proteins support these findings, suggesting that 7a is a promising candidate for developing into a potent anti-inflammatory clinical agent.