The potentially risky effects of metabolites of phthalates (mPAEs) on inflammation and immune function have attracted much attention in recent years. However, direct studies on the relationship between these metabolites and the systemic immune inflammatory index (SII) and systemic inflammatory response index (SIRI) are limited.

This cross-sectional study used generalized linear regression models (GLM), restricted cubic splines (RCS), weighted quantile sum (WQS), and Bayesian kernel-machine regression (BKMR) to analyze data from 2,763 U.S. adults aged between 20 and 80 years, obtained from the U.S. National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2018. The study aimed to investigate the relationship between urine samples of nine mPAEs and levels of SII/SIRI in a single, nonlinear, and mixed relationship and explored the robustness of the findings under single and mixed effects using two sensitivity analyses for completeness. In addition, the effects of six variables (age, sex, BMI, the percentage of total daily energy intake from ultra-processed foods (UPFs), total vegetable intake, and dietary supplements) on the association results were explored through subgroup analyses to identify potentially important confounders.

In single exposure analyses, mono-n-butyl phthalate (MnBP), mono-ethyl phthalate (MEP), and monobenzyl phthalate (MBzP) were positively associated with SII/SIRI. The findings from the two mixed exposure models demonstrated a positive association between the collective concentrations of mPAEs and levels of SII/SIRI, with MBzP being identified as a significant contributor to the urinary levels of mPAEs. The subgroup analysis results of the effects of single and mixed exposures show that the association between mPAEs and SII/SIRI is more significant in females, overweight/obese populations, young/middle-aged populations, and populations with high levels of intake of UPFs.

Positive associations were identified between mPAEs and SII/SIRI. MBzP was determined to have the most significant impact. The association between mPAEs and SII/SIRI is significantly influenced by female groups, young and middle-aged populations, overweight and obese individuals, as well as those with a higher intake of UPFs.

Atherosclerosis is a leading cause of global mortality, driven by complex interactions between genetic, metabolic, and environmental factors. Among these, hyperhomocysteinemia (HHcy) has emerged as a significant and modifiable risk factor, contributing to endothelial dysfunction, oxidative stress, and vascular inflammation. Despite increasing recognition of its role in atherogenesis, the precise mechanisms and clinical implications of HHcy remain incompletely understood, necessitating a comprehensive review to connect recent mechanistic insights with practical applications.

We analyzed the various mechanisms whereby HHcy accelerates the progression of atherosclerosis, and conducted a comprehensive review of publications in the fields of HHcy and atherosclerosis.

HHcy promotes atherosclerosis through several mechanisms, including inflammation, oxidative stress, epigenetic modification, and lipoprotein metabolism alteration. Moreover, this discussion extends to current strategies for the prevention and clinical management of HHcy-induced atherosclerosis.

This review consolidates and elucidates the latest advancements and insights into the role of HHcy in atherosclerosis. The comprehensive narrative connects fundamental research with clinical applications. Contemporary studies highlight the complex interplay between HHcy and atherosclerosis, establishing HHcy as not only a contributing risk factor but also an accelerator of various atherogenic processes.

Silicosis represents a formidable occupational lung pathology precipitated by the pulmonary assimilation of respirable crystalline silica particulates. This condition engenders a cascade of cellular oxidative stress via the activation of bioavailable silica, culminating in the generation of reactive oxygen species (ROS). Such oxidative mechanisms lead to irrevocable pulmonary impairment. Contemporary scholarly examinations have underscored the substantial antioxidative efficacy of platinum nanoparticles (PtNPs), postulating their utility as an adjunct therapeutic modality in silicosis management. The physicochemical interaction between PtNPs and silica demonstrates a propensity for adsorption, thereby facilitating the amelioration and subsequent pulmonary clearance of silica aggregates. In addition to their detoxifying attributes, PtNPs exhibit pronounced anti-inflammatory and antioxidative activities, which can neutralize ROS and inhibit macrophage-mediated inflammatory processes. Such attributes are instrumental in attenuating inflammatory responses and forestalling subsequent lung tissue damage. This discourse delineates the interplay between ROS and PtNPs, the pathogenesis of silicosis and its progression to pulmonary fibrosis, and critically evaluates the potential adjunct role of PtNPs in the therapeutic landscape of silicosis, alongside a contemplation of the inherent limitations associated with PtNPs application in this context.

Managing inflammation with the commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) represents a critical challenge in modern medicine because of its strong influence on the cyclooxygenase-1 (COX-1) enzyme might induce substantial adverse effects. Therefore, there is urgent necessity for the exploration of safer alternatives, particularly cyclooxygenase-2 (COX-2) inhibitors. This study aimed to address this issue through the synthesis and evaluation of 19 new chalcone derivatives (2a-m and 4a-f) for their in vitro anti-inflammatory activity against various biotargets including iNOS, COX-2, 5-LOX, PGE2, and TNFα. Moreover, these compounds showed moderate to strong anti-inflammatory activity in the carrageenan rat paw edema test. Compounds 2a, 2f, 2 h, 2 m, and 4b are promising candidates for the treatment of inflammatory diseases. In particular, compound 4b was demonstrated to be the most effective derivative as a nitric oxide release inhibitor, exhibiting a 61.7 % inhibition rate. It exhibited substantial selectivity for COX-2 (IC50 = 1.933 μM) compared to COX-1 (IC50 = 5.526 μM). Compound 4b exhibited notable inhibitory activity against 5-LOX (IC50 = 2.112 μM) and demonstrated considerable inhibitory activity against iNOS, PGE2, and TNF-α biotargets in LPS-stimulated RAW cells, with IC50 values of 114.18, 37.13, and 58.15 nM, respectively. The in vivo anti-inflammatory effects demonstrated the significant efficacy of compound 4b, as evidenced by a notable edema inhibition rate of 37.05 %, along with minimal ulcerogenic activity observed in the histopathological findings. In silico experiments demonstrated that the intermolecular contacts of the most active chemical 4b with the biotargets COX-2, 5-LOX, and iNOS were analyzed by docking, revealing significant binding interactions. The stability of the interactions between compound 4b and the targets COX-2, 5-LOX, and iNOS was assessed using a standard 100 ns atomistic dynamic simulation method. Various parameters derived from MD simulation trajectories were adjusted and validated to confirm the stability of the generated complexes under dynamic settings. Ultimately, compound 4b exhibited favorable physicochemical properties and satisfactory drug-likeness, indicating its potential as an oral anti-inflammatory agent, warranting additional structure-activity relationship investigation and optimization.

In this study, a series of novel ibuprofen (Ibu) hybrid molecules with aminothiazole heterocycles were designed, synthesized and evaluated for their anti-inflammatory potency in vitro and in vivo. Among all these derivatives, compounds 6 and 8 effectively inhibited the production of NO (with 87 %, 79 % NO-inhibitory rates, respectively) with minimal cytotoxic effect in RAW 264.7 macrophages. Anti-inflammatory mechanism studies revealed that representative compound 6 dose-dependently inhibited pro-inflammatory cytokines by blocking the activation of NF-κB signaling pathway in LPS stimulated RAW 264.7 macrophages. In vivo experiments showed that 10 mg/kg compound 6 had a good improvement effect in DSS-induced mouse acute colitis compared to Ibu. Our findings will provide new insights into the development of new drugs with anti-inflammatory functions.

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a critical player in cancer pathogenesis. Concurrently, inflammation, a key biological response to tissue injury or infection, significantly influences cancer development and progression. The interplay between ferroptosis and inflammation represents a promising yet underexplored area of research. This review synthesizes recent advances in understanding the molecular mechanisms governing their interaction, emphasizing how ferroptosis triggers inflammatory responses and how inflammatory mediators, such as TNF-α, regulate ferroptosis through iron metabolism and lipid peroxidation pathways. Key molecular targets within the ferroptosis-inflammation axis, including GPX4, ACSL4, and the NF-κB signaling pathway, offer therapeutic potential for cancer treatment. By modulating these targets, it may be possible to enhance ferroptosis and fine-tune inflammatory responses, thereby improving therapeutic outcomes. Additionally, this review explores the broader implications of targeting the ferroptosis-inflammation interplay in disease treatment, highlighting opportunities for developing innovative strategies to combat cancer. By bridging the gap in current knowledge, this review provides a comprehensive resource for researchers and clinicians, offering insights into the therapeutic potential of this intricate biological relationship.

Guided by the molecular modelling studies, here, we report the development of small molecules containing Pro-Pro, Gly-Pro-Pro ester motifs as dual inhibitors of COX-2 and 5-LOX enzymes. The synthesized compounds exhibited potent inhibitory activities against COX-2 and 5-LOX, with IC50 values in nanomolar range. Lineweaver-Burk plot analysis revealed that these molecules act as competitive inhibitors of COX-2 and 5-LOX. In vivo studies using the HET-CAM assay indicated that the compounds exhibit moderate to good anti-inflammatory effects. Hence, taking into account the physicochemical properties, including aqueous solubility, binding affinity to HSA and stability in blood plasma and liver microsomes, anti-inflammatory agents targeting dual pathways of arachidonic acid metabolism are identified.

Ganoderic acid A (GAA, C30H44O7) is one of the most abundant and active components of Ganoderic acids (GAs). GAs are highly oxidized tetracyclic triterpenoid compounds mainly derived from Ganoderma lucidum (Curtis) P. Karst (Chinese: ). GAA is primarily isolated from the fruiting body of Ganoderma lucidum. Modern pharmacological investigations have established the broad pharmacological effects of GAA, highlighting its notable influence on managing various conditions, including inflammatory diseases, neurodegenerative diseases, and cancer. This review provides a comprehensive summary of GAA's pharmacological activities.

The literature in this review were searched in PubMed and China National Knowledge Infrastructure (CNKI) using the keywords "Ganoderic acid A″, "Pharmacology" and "Pharmacokinetics". The literature cited in this review dates from 2000 to 2024.

According to the data, GAA exerts anti-inflammatory, antioxidant, antitumor, neuropsychopharmacological, hepatoprotective, cardiovascular, renoprotective, and lung protective effects by regulating a variety of signal transduction pathways, such as nuclear factor kappa-B (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), Toll-like receptor 4 (TLR4), nuclear factor erythroid 2-related factor-2 (Nrf2), phosphoinositide-3-kinase (PI3K)/AKT, mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), and Notch. Given its promising pharmacological activity, GAA holds excellent potential for treating human diseases. The pharmacokinetic properties of GAA have also been reviewed, revealing low bioavailability but high absorption and elimination rates. In addition, network pharmacology and molecular docking analyses verified that GAA plays a role in multiple diseases through MAPK3, tumor necrosis factor (TNF), caspase-3 (CASP3), peroxisome proliferator-activated receptor gamma (PPARG), and β-catenin (CTNNB1) signaling pathways.

GAA plays a pivotal role in various pathological and physiological processes, boasting broad application prospects. Furthermore, the network pharmacological results reveal the mechanisms of GAA in the treatment of multiple diseases. In the future, it is necessary to conduct further experiments to elucidate its specific mechanism of action, thus laying the foundation for the scientific utilization of GAA.

Steroidal and non-steroidal anti-inflammatory drugs are widely used for treating a spectrum of inflammatory conditions; however, their systemic adverse effects hinder their usage. Therefore, alternate therapeutic strategies are required to treat inflammatory disorders. Parthenin, a lactone derived from Parthenium hysterophorus, has demonstrated anti-inflammatory activity; however, its toxic nature limits its application. We proposed modifications of parthenin to enhance its efficacy while reducing toxicity. In this context, we screened parthenin derivatives for anti-inflammatory efficacy and identified dispiro-indanedione hybrid of parthenin (DIHP) as a potent anti-inflammatory agent. Macrophages were pre-treated with DIHP followed by LPS stimulation to evaluate the in-vitro anti-inflammatory and anti-oxidant activity. We assessed in-vivo anti-inflammatory effect of DIHP in carrageenan-induced paw edema and LPS-induced sepsis model. Our findings showed that DIHP exerts negligible effect on cell viability, effectively attenuates the production of inflammatory markers (NO, TNF-α, IL-6 &IL-1β) and down-regulates NF-κB, MAPK pathways in in-vitro and in-vivo system. Additionally, DIHP inhibited LPS-induced generation of prostaglandin E2, leukotriene B4, ROS and upregulated the expression of superoxide dismutase, catalase, nuclear factor-E2-related factor 2 and peroxisome proliferator-activated receptor gamma. Furthermore, DIHP effectively reduced carrageenan-induced paw edema and curtailed the levels of liver, and kidney damage markers (AST, ALT, CRE, and BUN), protected the lung, liver and kidney against pathological damage and enhanced the survival rate in LPS-challenged mice. DIHP demonstrated comparable efficacy to dexamethasone in reducing inflammatory markers. In conclusion, our study strongly suggests that DIHP curtailed inflammation and oxidative stress by down regulating NF-κB and MAPK pathways and enhanced anti-oxidant response.

This research was designed to explore the expression patterns and functional significance of hypoxia-inducible factor-1α (HIF-1α) in the inflammatory response associated with Aspergillus fumigatus (A. fumigatus) keratitis.

Mouse models of A. fumigatus keratitis were created by scraping the corneal epithelium and applying A. fumigatus on the corneal surface. In the in vitro experiments, human corneal epithelial cells (HCECs) and THP-1 macrophages stimulated by A. fumigatus were used to investigate the cellular responses. HIF-1α was inhibited using LW6. Western blot, immunofluorescence, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were performed to assess the expression levels of HIF-1α in A. fumigatus keratitis. The inflammatory response was evaluated using clinical scoring, corneal thickness measurements, hematoxylin and eosin (H&E) staining, corneal fluorescein sodium staining, and a cell scratch test. The polarization of macrophages was determined using flow cytometry. The molecular mechanisms of HIF-1α were assessed by qRT-PCR and Western blot.

In A. fumigatus keratitis, the expression of HIF-1α was significantly increased at both the mRNA and protein levels. Compared with the controls, HIF-1α inhibitor accelerated corneal epithelial repair, reduced the infiltration of macrophages, induced shift in macrophage polarization, and attenuated the inflammatory response. HIF-1α exerts a pro-inflammatory effect in A. fumigatus keratitis by modulating the expression of inflammatory mediators and engaging in pyroptosis via the caspase-8/GSDMD signaling pathway.

In conclusion, HIF-1α promotes A. fumigatus keratitis by inhibiting corneal epithelial repair and promoting inflammation, leading to increased severity of the disease.

Natural compounds have garnered significant attention as potential therapeutic agents due to their inherent properties. Their notable qualities, including safety, efficacy, favorable pharmacokinetic properties, and heightened effectiveness against certain diseases, particularly inflammatory conditions, make them particularly appealing. Among these compounds, curcumin has attracted considerable interest for its unique therapeutic properties and has therefore been extensively studied as a potential therapeutic agent for treating various diseases. Curcumin exhibits diverse anti-inflammatory, antioxidant, and antimicrobial effects. Curcumin's immune system regulatory ability has made it a promising compound for treatment of various inflammatory diseases, such as psoriasis, atherosclerosis, asthma, colitis, IBD, and arthritis. Among the signaling pathways implicated in these conditions, the CD40 receptor together with its ligand, CD40L, are recognized as central players. Studies have demonstrated that the interaction between CD40 and CD40L interaction acts as the primary mediator of the immune response in inflammatory diseases. Numerous studies have explored the impact of curcumin on the CD40:CD40L pathway, highlighting its regulatory effects on this inflammatory pathway and its potential therapeutic use in related inflammatory conditions. In this review, we will consider the evidence concerning curcumin's modulatory effects in inflammatory disease and its potential therapeutic role in regulating the CD40:CD40L pathway.

Formyl peptide receptor 2 (FPR2) is a G protein-coupled receptor with seven transmembrane domains, widely distributed in human cells. It plays a crucial role in inflammation-related diseases. Known for its "double-edged sword" nature, FPR2 can bind a variety of exogenous and endogenous ligands, mediating both pro-inflammatory and anti-inflammatory responses in tissues such as eyes, liver, joints, lungs, nerves, and blood vessels. FPR2's bioactivities are regulated by a complex network of genes and signaling pathways. However, the precise regulatory mechanisms governing its functions in different inflammatory conditions are still not well understood. This review summarizes the FPR2's activities in various inflammation-related diseases and looks into its potential as a therapeutic target. This review highlights recent advances in developing exogenous agonists for FPR2 and discusses receptor expression across species to support nonclinical research. Overall, this review aims to clarify FPR2's role in inflammation and provide insights for the development of new drugs against inflammatory diseases.

Host-directed therapies (HDTs) have been investigated as a potential solution to combat intracellular and drug-resistant bacteria. HDTs stem from extensive research on the intricate interactions between the host and intracellular bacteria, leading to a treatment approach that relies on immunoregulation. To improve the bioavailability and safety of HDTs, researchers have utilized diverse drug delivery systems (DDS) to encapsulate and transport therapeutic agents to target cells. In this review, we first introduce the three mechanisms of bactericidal action and intracellular bacterial evasion: autophagy, reactive oxygen species (ROS), and inflammatory cytokines, with a particular focus on autophagy. Special attention is given to the detailed mechanism of xenophagy in clearing intracellular bacteria, a crucial selective autophagy process that specifically targets and degrades intracellular pathogens. Following this, we present the application of DDS to modulate these regulatory methods for intracellular bacteria elimination. By integrating insights from immunology and nanomedicine, this review highlights the emerging role of DDS in advancing HDTs for intracellular bacterial infections and paving the way for innovative therapeutic interventions.

Disruption of local microbial irritation and host immune response can result in inflammation and tissue destruction in periodontitis. Studies on the modulation of macrophage polarization could help attenuate immune responses in periodontal tissues. To investigate the effect of ubiquitin-specific protease-7 (USP7) and its inhibitor P5091 on the polarization of macrophages in periodontitis, gene expression in periodontitis tissues and normal control were analyzed via single-cell RNA sequencing data and mice model experimental periodontitis. RAW264.7 cells were induced to M1 polarization with LPS + IFN-γ and M2 polarization with IL-4. USP7 was knocked down using lentivirus, and the effect of USP7 inhibitor P5091 on macrophage polarization was comparatively analyzed. The expression of Usp7 and polarization markers were detected by qRT-PCR. Western blot was used to examine the polarization markers and pathway-associated proteins. Results indicated that USP7 expression was elevated in tissues affected by periodontitis. Periodontitis macrophages and M1 polarized macrophages had higher USP7 expression. Knockdown of USP7 revealed an inhibition of both M1 and M2 macrophage polarization. Inhibition of USP7 with P5091 resulted in the decreased expression of M1 polarization markers and phosphorylation of P65, but the increased expression of M2 polarization markers and phosphorylation of STAT6. In conclusion, USP7 is involved in regulating macrophage polarization in periodontitis and its inhibitor P5091 may contribute to the prevention of periodontitis.

Ion channels, membrane proteins that facilitate the transport of various inorganic ions across hydrophobic cellular lipid membranes, are ubiquitous in a wide variety of cell and tissue types. They are involved in establishing the cell membrane potential and play a role in various physiological activities by regulating ion concentrations within the cell. Dendritic cells (DCs) are specialised antigen-presenting cells found mainly on the surface of the body (skin and mucous membranes), in the mesenchyme of most organs, in the T-cell compartment of the spleen and in lymph nodes. DCs exert an important influence on the regulation of inflammation by activating T cells and producing cytokines. Studies have shown that ion channels expressed in DCs contribute to the regulation of the immune response, making them a key component of the immune system. This review summarises the major scientific advances in understanding the functional impact of ion channels (calcium channels, sodium channels and aquaporin) in DCs, including the regulation of inflammatory responses, antigen presentation, maturation, migration and cytokine production, to inform ongoing studies of ion channel function in DCs.

Inflammation resolution is governed by specialized pro-resolving mediators (SPM), mainly formed from omega-3 polyunsaturated fatty acids (n-3 PUFA) by lipoxygenases (LOX), which terminate inflammatory processes and facilitate healing and tissue repair. Promoting endogenous SPM formation, besides therapeutic SPM application, is an innovative concept for intervention in inflammatory diseases, achievable by allosteric 15-LOX activation. Here, targeted screening of the 29 most frequently applied anti-inflammatory natural products using lipid mediator metabololipidomics uncovered the acylphloroglucinols hyperforin, arzanol, garcinol, Myrtucommulone A and the lignan magnolol as potent 15-LOX activators to elicit robust SPM production in resting human M2-like macrophages. Simultaneous n-3 PUFA supplementation synergistically enhanced SPM formation in these M2-like macrophages, most strikingly with magnolol. Comprehensive targeted metabololipidomics in activated human polymorphonuclear leukocytes, monocytes, and M1-/M2-like macrophages revealed shifts from pro-inflammatory cyclooxygenase (COX) and 5-LOX products to pro-resolving 15-LOX products by magnolol and acylphloroglucinols. Finally, using zymosan-induced peritonitis in mice, application of a magnolol/n-3 PUFA combination confirmed synergistic SPM elevation in vivo. Together, we established an approach based on synergism of natural allosteric 15-LOX activators and supplemented n-3 PUFA to accomplish SPM-based resolution pharmacology.

The intratumoral microbiota, as an important component of the tumor microenvironment, is increasingly recognized as a key factor in regulating responses to cancer immunotherapy. Recent studies have revealed that the intratumoral microbiota is not uniformly distributed but instead exhibits significant spatial heterogeneity, with its distribution patterns influenced by factors such as tumor anatomy, local immune status, and therapeutic interventions. This spatial heterogeneity not only alters the interactions between microbes and the host immune system but may also reshape the immunogenic and immunosuppressive landscapes of tumors. The enrichment or depletion of microbiota in different tumor regions can influence immune cell infiltration patterns, metabolic pathway activities, and immune checkpoint molecule expression, thereby driving the development of resistance to immunotherapy. Moreover, certain bacterial metabolites form concentration gradients between the tumor core and margins, thereby regulating immune cell function. Therefore, understanding and manipulating the spatial distribution of intratumoral microbiota, particularly in resistant patients, holds promise for developing new strategies to overcome immunotherapy resistance. In the future, precise modulation strategies targeting microbial spatial heterogeneity, such as engineered bacterial vectors, probiotic combinations, and phage therapy, may open new avenues for immunotherapy.

The severe adverse effects associated with imbalanced cyclooxygenase-2 (COX-2) inhibition continue to pose significant challenges in the development of contemporary anti-inflammatory drugs. In recent years, the approach to COX-2 inhibitor drug development has shifted from a focus on highly selective inhibition of COX-2 to a strategy that emphasizes more moderate selectivity. The amino acid sequence and structural similarities between inducible COX-2 and constitutive cyclooxygenase-1 (COX-1) isoforms present both substantial opportunities and challenges for the design of next generation of balanced COX-2 inhibitors. As part of our ongoing research into the discovering novel and safer COX-2 inhibitors, we reported herein a highly potent and balanced COX-2 inhibitor 21 d (IC50 value=1.35 μM, selectivity profile (IC50 (COX-1)/IC50 (COX-2)=22.34)). In vivo assays demonstrated that 21 d significantly alleviated histological damage and provided robust protection against dextran sulfate sodium (DSS)-induced acute colitis.

Naturally occurring furylidene tetronic acids were rare and structurally unique, typically with a furylidene connected to a furan-2,4-(3H, 5H)dione (tetronic acid moiety). In the current study, seven furylidene tetronic acid derivatives (1-7) were isolated and identified from the endophytic fungus Hypoxylon monticulosum ZZ14, including three new ones, hypoxytetronic acids A and B (1 and 2) and 2',3'-dihydronodulisporacid A methyl ester (3). Compounds 1 and 2 possess an unusual skeleton, with two tetrahydrofurans attached to the tetronic acid moiety. Their absolute configurations were elucidated by custom-DP4+ probability analysis of NMR chemical shifts and ECD calculations. Nodulisporacid A methyl ester (7) significantly inhibited the production of interleukin 6 (IL-6), interleukin 10 (IL-10), nitric oxide (NO), and inducible nitric oxide synthase (iNOS), comparable to the positive control dexamethasone. Several analogues of nodulisporacid A methyl ester were synthesized, and structure-activity relationship studies were performed, suggesting that the conjugated fragment of 1/2/3/1'/2'/3' and the methyl ester group may be the pharmacophores.

Glioblastoma (GBM) is the most aggressive primary intracranial tumor, with glioblastoma stem cells (GSCs) enforcing the intratumoral hierarchy. The inflammatory microenvironment influences tumor development at varying stages, while the underlying mechanism of GSCs facing pro-inflammatory stress remains unclear. Here, we show that, in human GBM, pro-inflammatory stress from pro-inflammatory macrophages (pTAMs) maintains GSC proliferation and self-renewal. Tumor necrosis factor alpha-induced protein 6 (TNFAIP6), as a responder in patient-derived GSCs to pro-inflammatory stress tumor necrosis factor alpha (TNF-α) from human pTAMs, promotes tumor growth through binding epidermal growth factor (EGF) and prolonging EGF receptor (EGFR)-phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling activation. Meanwhile, pro-inflammatory stress-induced patient-derived GSCs secrete TNFAIP6 to transform macrophage phenotype from pTAMs to inflammatory-suppressive macrophages (sTAMs). Collectively, pharmacological or genetic disruption of TNFAIP6 autocrine and paracrine communication between patient-derived GSCs and TAMs inhibited GSC proliferation and self-renewal in vitro and in patient-derived xenograft tumor-bearing mice, suggesting that TNFAIP6 is an effective target for GBM therapy.

Chemotherapy drugs used in inflammatory disorders and some cancers, while effective, often cause diverse side toxic effects, prompting research into alternatives to ameliorate damage in healthy tissues. One strategy is to encapsulate doxorubicin (DOX) chemotherapeutic agents into nano-vehicles, such as organic-functionalized mesoporous nanoparticles, to reduce systemic leakage and adverse effects, such as inflammation. This study analyzes the toxicological and anti-inflammatory effects of a drug-delivered system (DDS) based on MCM-41 mesoporous silica nanoparticles modified with a pH-sensitive poly(β-amino ester) named MCM-41-PbAE. The effects of both blank nanoparticles (MCM-41-PbAE) and those with encapsulated DOX (MCM-41-PbAE-DOX) were evaluated in LPS-stimulated mouse macrophages and in an in vivo inflammation model. Characterization of nanoparticles was carried out through TEM, DLS, FTIR Z-potential, and thermogravimetric tests. Macrophages were treated with MCM-41-PbAE and MCM-41-PbAE-DOX particles at several concentrations, and the production of proinflammatory and anti-inflammatory cytokines, nitric oxide (NO), and hydrogen peroxide (H2O2) levels were determined. Toxicological evaluation was performed in BALB/c mice and the in vivo anti-inflammatory effect was evaluated in a carrageenan-induced paw edema model and the measuring serum levels of pro-inflammatory cytokines. Results indicated that MCM-41-PbAE-DOX significantly reduces NO and H2O2 levels and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in dose-manner without affecting cell viability or causing toxicity in mice. Conversely, a reduction in carrageenan-induced paw edema and decreased levels of proinflammatory cytokines were noted, indicating the potential advantage of encapsulating DOX within MCM-41-PbAE nanoparticles, which could inhibit inflammation without compromising healthy cell viability.

The downstream signaling pathways of TLR activation involve a family of adaptor proteins, including MYD88, TIRAP, TRIF, TRAM, and SARM1. The first four proteins stimulate inflammatory and antiviral responses, playing crucial roles in innate immunity against various pathogens. In contrast, SARM1 promotes immunity to microorganisms in invertebrate animals independently of TLRs, and negatively regulates inflammatory responses in metazoan organisms. SARM1 inhibits TRIF, reduces the activation of various inflammasomes, and induces mitochondrial damage and cell death to eliminate hyperactivated cells. This regulation is essential to ensure timely control of immune responses and to prevent excessive inflammation. Recently, it was discovered that SARM1 can hydrolyze NAD, a critical component of cellular metabolism. The reduction of NAD levels by SARM1 is linked to the progression of Wallerian degeneration following neuronal injury and may also play a role in the immunoregulation of lymphoid and myeloid cells. Since SARM1 can be pharmacologically modulated, it presents promising opportunities for developing treatments for inflammatory and neurodegenerative diseases.

Type I interferons (IFNs) generate strong antiviral immunity following viral infection in mice and humans. These type I IFNs are encoded by at least 14 IFNα genes and a single IFNβ gene. We showed that the absence of one of the IFNα genes (IFNα2A-/-) affected latency levels in herpes simplex virus type 1 (HSV-1) ocularly infected mice but not in infected control mice, and the absence of IFNα2A did not affect viral reactivation in ocularly infected mice. Since the role of IFNβ in HSV-1 latency reactivation and the potential effect of latency-associated transcript (LAT) on IFNβ activity is not known, we ocularly infected IFNβ-/- mice with different doses of LAT-plus [LAT(+)] and LAT-minus [LAT(-)] viruses. Wild-type (WT) control mice and IFNβ-/- mice were infected similarly. Virus titers in the eye, viral and cellular transcripts in the eye and trigeminal ganglia (TG) of infected mice on days 3 and 5 post-infection, eye disease, survival, latency-reactivation levels, and T cell exhaustion were measured in latently infected mice. Virus replication and viral and cellular transcripts in the eye of infected IFNβ-/- mice were similar to those in WT mice, while eye disease and survival in IFNβ-/- mice differed significantly from WT mice. WT mice infected with LAT(-) virus showed reduced latency, slower reactivation, and less T cell exhaustion than mice infected with LAT(+) virus. However, using different doses of each virus, latency levels, time of reactivation, and T cell exhaustion were similar between LAT(+) and LAT(-) viruses. These results suggest that the absence of IFNβ expression compensates for the function of LAT with regard to levels of latency, T cell exhaustion, and reactivation but does not affect viral and cellular transcripts during primary infection.IMPORTANCEInterferon β (IFNβ) is a type I interferon that plays an important role in controlling primary herpes simplex virus type 1 (HSV-1) infection. To evaluate the importance of IFNβ on HSV-1 latency reactivation and its relationship to LAT, we infected IFNβ-/- mice with LAT(+) and LAT(-) viruses. In the absence of IFNβ, latency levels in mice infected with LAT(-) virus were similar to those of mice infected with LAT(+) virus. The absence of IFNβ also reduced the time of reactivation in mice infected with LAT(-) virus to that of LAT(+) virus. Our results show a strong correlation between the functions of LAT and IFNβ during latent but not primary stages of HSV-1 infection.

Gymnopodium floribundum Rolfe, known locally as "Dzidzilche" or "Ts'its'ilche," is a native species from Mexico and Central America. In Mayan communities, this plant is used to relieve inflammation and diverse respiratory diseases such as colds, catarrh, bronchitis, and asthma. Usually, a decoction of leaves or flowers is prepared and administered orally.

This research explores the anti-inflammatory effects of the methanol extract of Gymnopodium floribundum Rolfe leaves (MGF) using in vitro and in vivo animal models of inflammation.

MGF was characterized by GC-MS, and cytotoxicity was assessed using hemolysis and MTT assays. The antiphlogistic effect in vitro was measuring the release of cytokines, hydrogen peroxide, and nitric oxide in macrophages stimulated with LPS. Additionally, anti- and pro-inflammatory cytokines, prostaglandins, and leukotrienes in serum were quantified in carrageenan-induced mouse paw edema. Finally, 1-fluoro-2,4-dinitrobenzene (DNFB)-induced delayed-type hypersensitivity and TPA-induced ear edema models were analyzed.

Compounds found in MGF, such as D-pinitol and protocatechuic (3,4-dihydroxybenzoic) acid, are reported to exert anti-inflammatory effects. MGF showed no hemolytic or cytotoxic effects. Nevertheless, it displayed in vitro anti-inflammatory activity by decreasing the release of IL-6, IL-1β, TNF-α, hydrogen peroxide, and nitric oxide levels; on the other hand, it increased IL-10 production. Furthermore, the MGF significantly reduced inflammation in mouse models and reduced the release of leukotrienes, prostaglandins, and pro-inflammatory cytokines.

Gymnopodium floribundum Rolfe exhibits anti-inflammatory activity by suppressing pro-inflammatory mediators, altering cell migration mechanisms, and raising IL-10 production.

Myelodysplastic neoplasms (MDS) represent a heterogeneous group of malignant hematopoietic stem and progenitor cell (HSPC) disorders characterized by cytopenia, ineffective hematopoiesis, as well as the potential to progress to acute myeloid leukemia (AML). The pathogenesis of MDS is influenced by intrinsic factors, such as genetic insults, and extrinsic factors, including altered bone marrow microenvironment (BMM) composition and architecture. BMM is reprogrammed in MDS, initially to prevent the development of the disease but eventually to provide a survival advantage to dysplastic cells. Recently, inflammation or age-related inflammation in the bone marrow has been identified as a key pathogenic mechanism for MDS. Inflammatory signals trigger stress hematopoiesis, causing HSPCs to emerge from quiescence and resulting in MDS development. A better understanding of the role of the BMM in the pathogenesis of MDS has opened up new avenues for improving diagnosis, prognosis, and treatment of the disease. This article provides a comprehensive review of the current knowledge regarding the significance of the BMM to MDS pathophysiology and highlights recent advances in developing innovative therapies.

The relationship between the innate immune signal and the start of the adaptive immune response is the central idea of this theory. By controlling the inflammatory and tissue-repair reactions to damage, the Toll-like receptors (TLRs), as a family of PRRs, have attracted increasing attention for its function in protecting the host against infection and preserving tissue homeostasis. Microbial infection, damage, inflammation, and tissue healing have all been linked to the development of malignancies, especially gastrointestinal (GI) cancers. Recently, increased studies on TLR recognition and binding, as well as their ligands, have significantly advanced our knowledge of the various TLR signaling pathways and offered therapy options for GI malignancies. Upon activation by pathogen-associated or damage-associated molecular patterns (DAMPs and PAMPs), TLRs trigger key pathways like NF-κB, MAPK, and IRF. NF-κB activation promotes inflammation, cell survival, and proliferation, often contributing to tumor growth, metastasis, and therapy resistance. MAPK pathways similarly drive uncontrolled cell growth and invasion, while IRF pathways modulate interferon production, yielding both anti-tumor and protumor effects. The resulting chronic inflammatory environment within tumors can foster progression, yet TLR activation can also stimulate beneficial anti-tumor immune responses. However, the functions of TLR expression in GI cancers and their diagnostic and prognostic along with therapeutic value have not yet entirely been elucidated. Understanding how TLR activation contributes to anti-cancer immunity against GI malignancies may hasten immunotherapy developments and increase patient survival.

The aim of our study was to examine the stability of pentraxin 3 (PTX3) in serum and urine samples during 4-week storage at -20 °C.

Ten routine leftover serum and urine samples were used in this study. The samples were stored at -20 °C over 4 weeks and analyzed each week in a single batch using the Human pentraxin 3 ELISA kit (BioVendor Group). Stability was expressed as a percentage difference between the initial measurement and the measurements taken weekly. Total error (33%) was used as the performance criterion for stability.

The concentration of PTX3 decreases with time during storage at -20 °C in both serum and urine. The percentage difference exceeded the set criterion in serum samples at the third week of storage (percentage difference = -23.5% [95% CI, -36.6% to -10.5%]) and at the first week of storage in urine samples (percentage difference = -41.5% [95% CI, -63.1% to ‒19.8%]).

Pentraxin 3 can be stored in serum samples for a maximum of 2 weeks at -20 °C before analysis to measure representative results. Because PTX3 is not stable in urine samples, such samples should be analyzed on the day of sample collection.

α-Mangostin, a bioactive xanthone derived from the Garcinia mangostana L. Clusiaceae (G. mangostana) fruit, has demonstrated significant anti-inflammatory and immunomodulatory properties. Chronic inflammation plays a critical role in the pathogenesis of various diseases, including metabolic disorders, autoimmune conditions, and cancer. Conventional anti-inflammatory therapies, such as non-steroidal anti-inflammatory drugs (NSAIDs), often carry undesirable side effects, prompting the need for safer, natural alternatives. This review consolidates the existing literature on the mechanisms by which α-mangostin exerts its anti-inflammatory effects, including the suppression of pro-inflammatory cytokines, modulation of immune cell activity, and inhibition of key signaling pathways such as nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). Additionally, α-mangostin exhibits immunomodulatory properties by influencing both innate and adaptive immune responses, affecting macrophage polarization, T cell differentiation, and cytokine production. Its efficacy has been observed in numerous disease models, including joint disorders, digestive and metabolic conditions, hepatic diseases, neurological disorders, and respiratory ailments. The potential therapeutic applications of α-mangostin as an anti-inflammatory agent warrant further investigation through preclinical and clinical studies to validate its efficacy and safety.

More than 90% of drug candidates used in the drug development pipeline and about 40% of drugs on the market are poorly soluble in water based on the definition of the biopharmaceutical classification system. The advent of drug delivery approaches has represented a striking tool to overcome the challenges associated with the use of hydrophobic drugs, such as their low bioavailability and off-target effects. Drug carrier formulations composed of biodegradable and biocompatible polymers, such as polypeptides, have been explored as platforms to host poorly water-soluble drugs to prolong drug circulation, enhance their safety, reduce their immunogenicity, and promote their controlled release. In this work, we evaluated three strategies-co-precipitation, post-encapsulation, and conjugation-to incorporate a hydrophobic model drug, i.e., curcumin (CUR), into biodegradable multilayer capsules fabricated via a layer-by-layer (LbL) approach. Poly(L-lysine) (PLys) and poly(L-glutamic acid) (PGlu) were adopted as building blocks and alternately assembled onto calcium carbonate (CaCO3) microparticles to build a polypeptide-multilayer membrane, which acted as a barrier to control the release of the drug. The application of our three formulations in in vitro inflammatory models of THP-1 derived human macrophages and murine microglia showed a reduction of the inflammation with the suppression of three pivotal pro-inflammatory cytokines (i.e., interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α). Moreover, the intracellular release of CUR detected upon uptake studies on activated microglia suggested that our systems could represent a potential therapeutic approach to reduce acute neuroinflammation and modulate microglia phenotype.

Flap necrosis post-operation disturbs surgeons during plastic and reconstructive surgery. This is caused by hypoperfusion and subsequent ischemia-reperfusion injury, where restricted blood flow followed by restored circulation paradoxically exacerbates tissue damage. Mesenchymal stem cells, which show multidirectional differentiation, provide hematopoietic support and are involved in immune regulation and anti-fibrosis, have inspired research on improving the blood supply of flaps.

Primary human umbilical cord mesenchymal stem cells (HuMSCs), were obtained and subcultured for expansion. The cells of the third generation were incubated in a gelatin sponge. Thirty Kunming mice were randomly divided into three groups, and saline, HuMSCs, and HuMSCs-CM were injected preoperatively into the skin of the back. The vessel density was assessed on the tenth day. Forty-eight Kunming mice were divided into two groups. Group A was subdivided into the saline group, HuMSCs, and HuMSCs-CM groups and pretreated as described above. In Group B, the intervention was changed from injection to subcutaneous embedding. Random flaps were made on the back in both groups on the tenth day after pretreatment. The survival rate of the flap was calculated on the seventh day.

HuMSCs-CM significantly increased the microvessel density on the tenth day after pretreatment. The flap survival rate was higher in the cell and CM groups, rising from approximately 13% to 60% in Group A, and to about 75% in Group B. Moreover, subcutaneous embedding of cell-carrying gelatin sponges improved flap survival compared to other interventions.

Improved cell incubation conditions can enhance its utility. The application of HuMSCs and their conditioned medium promoted the survival of the flap by inducing neovasculogenesis.

Psoriasis and atopic dermatitis (AD) are both chronic inflammatory skin diseases. Their pathogenesis remains incompletely understood. The polarization states of macrophages, as a crucial part of the innate immune system, are influenced by various factors such as cytokines, inflammatory mediators, and epigenetics. Research has demonstrated that macrophages play a "double-edged sword" role in the pathological process of inflammatory skin diseases: they both drive inflammation progression and participate in tissue repair. This article summarizes the roles of macrophages in the inflammatory development and tissue homeostasis of psoriasis and atopic dermatitis. It explores the impact of different factors on macrophages and inflammatory skin diseases. In conclusion, understanding the classification and plasticity of macrophages is crucial for a deeper understanding of the pathogenesis of psoriasis and AD and the development of personalized treatments.

In the treatment of infectious keratitis, therapeutic strategies often prioritize enhancing bactericidal efficacy. However, endotoxins released from Gram-negative bacteria cause inflammatory reaction, leading to corneal structural damage and scar formation. Given that polymyxin B (PMB) can bind and neutralize lipopolysaccharide (LPS), this study employs large-pore mesoporous silica nanoparticles (lMSNs) grafted with PMB as carriers for cationic antibacterial carbon quantum dots (CQDs) to prepare CQD@lMSN-PMB, which enables synchronous sterilization and endotoxin neutralization. In the acidic infectious microenvironment, the accelerated release of CQDs eliminates 99.88% bacteria within 2 h, effectively substituting immune mediated sterilization. Notably, CQD@lMSN-PMB exhibits exceptional LPS neutralization performance (2.22 µg LPS/mg CQD@lMSN-PMB) due to its high specific surface area. In an infectious keratitis model, inflammation subsides significantly within the first day of CQD@lMSN-PMB intervention and is completely resolved by day 3. By day 2, interleukin-1β, interleukin-6 and tumor necrosis factor-α in CQD@lMSN-PMB group decrease by 86.99%, 91.15%, and 77.56%, respectively, compared to the CQDs-only sterilization group. Ultimately, corneal integrity and transparency are preserved, with suppressed expressions of fibrosis-related factors including matrix metalloproteinase 9, transforming growth factor-β and α-smooth muscle actin. Therefore, this synchronous sterilization and endotoxin neutralization strategy outperforms monotherapy strategies focused solely on sterilization or endotoxin neutralization.

There is increasing apprehension regarding the rising prevalence of microplastics (MPs) in aquatic ecosystems. Although MPs cause toxicological effect on fish via diverse pathways, the precise immunotoxicological mechanism is yet to be fully understood. Utilizing zebrafish in early developmental stages and zebrafish embryonic fibroblast (ZF4) as models, this study delved into the immune response elicited by polystyrene MPs (PS-MPs). It was observed that larvae predominantly accumulate 3 μm PS-MPs in their intestines through ingestion, leading to notable changes in locomotor behavior and histopathological alterations. Further investigation revealed that short-term exposure to PS-MPs triggers oxidative stress (OS) and inflammation in zebrafish. This is evidenced by the upregulation of OS and inflammation-related genes, increased levels of reactive oxygen species (ROS), malonaldehyde (MDA), and inflammatory cytokines, altered activities of antioxidant enzymes, along with induced recruitment of leukocyte in larvae. Cellular assays confirmed that PS-MPs elevate intracellular ROS in ZF4 cells and enhance the nuclear translocation of NF-κB P65. Notably, the activation of NF-κB and the upsurge in inflammatory cytokines can be mitigated by inhibiting ROS. This research highlights the significance of the ROS-triggered NF-κB signaling cascade in PS-MPs-mediated inflammation within zebrafish, illuminating the possible processes that underlie the innate immune system of fish toxicity caused by MPs.

Inflammation processes can cause mild to severe damage in the human body and can lead to a large number of inflammation-related diseases (IRD) such as cancer, neural, vascular, and pulmonary diseases. Limitations of anti-inflammatory drugs (AID) application are reflected in high therapeutic doses, toxicity, low bioavailability and solubility, side effects, etc. Polymeric nanosystems (PS) have been recognized as a safe and effective technology that is able to overcome these limitations by AID encapsulation and is able to answer to the specific demands of the IRD treatment. PS are attracting great attention due to their versatility, biocompatibility, low toxicity, fine-tuned properties, functionality, and ability for precise delivery of anti-inflammatory drugs to the targeted sites in the human body. This article offers an overview of three classes of polymeric nanosystems: a) dendrimers, b) polymeric micelles and polymeric nanoparticles, and c) polymeric filomicelles, as well as their properties, preparation, and application in IRD treatment. In the future, the number of PS formulations in clinical practice will certainly increase.

In this study, epicatechin gallate (ECG), a natural anti-inflammatory agent, was conjugated onto dialdehyde starch (DAS) to achieve high physiological stability. The anti-inflammatory effect of DAS-ECG conjugate was evaluated by lipopolysaccharide (LPS)-stimulated RAW264.7 cells and dextran sulfate sodium (DSS)-induced colitis mice models. Results showed that 25-800 μg/mL of DAS-ECG conjugate was non-cytotoxic to RAW264.7 cells. DAS-ECG conjugate effectively inhibited the abnormal morphology, the production of nitric oxide, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and reactive oxygen species, and the apoptosis of LPS-stimulated RAW264.7 cells in a dose-dependent manner. DAS-ECG conjugate significantly reduced the disease activity index, thymus atrophy, spleen enlargement, colon shortening and colon damage of DSS-induced colitis mice. Meanwhile, DAS-ECG conjugate remarkably reduced the levels of TNF-α, IL-6, IL-1β and malondialdehyde but increased the levels of superoxide dismutase and glutathione in the colon tissue of DSS-induced colitis mice. Moreover, DAS-ECG conjugate increased the relative abundance of beneficial bacteria (Akkermansia, Candidatus_Saccharimonas, unclassified_f_Muribaculaceae, Alistipes and Parabacteroides), promoted the production of short-chain fatty acids, and decreased the relative abundance of harmful bacterium (norank_f_Ruminococcaceae) in DSS-induced colitis mice. Therefore, DAS-ECG conjugate could be considered as a promising anti-inflammatory agent.

The most prevalent and bioactive cucurbitacin is Cucurbitacin B (CuB, C32H46O8), which is a tetracyclic triterpene chiefly present in the Cucurbitaceae family. CuB has a wide spectrum of pharmacological properties namely antioxidant, anticancer, hepatoprotective, anti-inflammatory, antiviral, hypoglycaemic, insecticidal, and neuroprotective properties, owing to its ability to regulate several signaling pathways, including the Janus kinase/signal transducer and activator of transcription-3 (JAK/STAT3), AMP-activated protein kinase (AMPK), nuclear factor (NF)-κB, nuclear factor erythroid 2-related factor-2/antioxidant responsive element (Nrf2/ARE), phosphoinositide 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK), Hippo-Yes-associated protein (YAP), focal adhesion kinase (FAK), cancerous inhibitor of protein phosphatase-2A/protein phosphatase-2A (CIP2A/PP2A), Wnt and Notch pathways. The present review highlights the medicinal attributes of Cucurbitacin B (CuB) with special emphasis on their signaling pathways to provide key evidence of its therapeutic utility in the near future.

Osteoimmunomodulation is a strategy to promote bone regeneration in implants by modifying the immune environment. CpG-containing oligonucleotides type C (CpG ODN C) and Polyinosinic:polycytidylic acid (Poly[I:C]) are analogs of microbial nucleic acids that have been studied for various immunotherapeutic applications. This research investigates the potential of CpG ODN C and Poly(I:C) as an osteoimmunomodulatory agent for bone regenerative purposes. We encapsulated each nucleic acid in a lipid-based nanoparticle to facilitate the delivery into intracellular pathogen recognition receptors in immune cells. The lipid-based nanoparticles were ±250 nm in size with a negative charge (-36 to -40 mV) and an encapsulation efficiency of ±60 %. Lipid-based nanoparticles containing nucleic acids, Lip/CpG ODN C and Lip/Poly(I:C), increased the production of TNF, IL-6, and IL-10 by primary human macrophages compared to free-form nucleic acids. Conditioned medium from macrophages treated with CpG ODN C (10 µg/ml) and Lip/CpG ODN C (0.1, 1, and 10 µg/ml) promoted osteoblast differentiation of human mesenchymal stromal cells by 2.6-fold and 3-fold, respectively; no effect was seen for Lip/Poly(I:C). Bone implants were prepared, consisting of a biphasic calcium phosphate scaffold, bone morphogenetic protein (BMP) 2, and lipid-based nanoparticles suspended in gelatin methacryloyl (GelMA) hydrogel. Implants were evaluated for de novo bone formation in an extra-skeletal implantation model in rabbits for 5 weeks. Based on the particles suspended in GelMA, six groups of implants were prepared: Lip/CpG ODN C, Lip/Poly(I:C), Lip (empty), CpG ODN C, Poly(I:C), and a control group consisting of empty GelMA. After 5 weeks, healthy bone tissue formed in all of the implants with active osteoblast and osteoclast activity, however, the amount of new bone volume and scaffold degradation were similar for all implants. We suggest that the working concentrations of the nucleic acids employed were inadequate to induce a relevant inflammatory response. Additionally, the dosage of BMP-2 used may potentially mask the immune-stimulatory effect. Lip/CpG ODN C holds potential as a bioactive agent for osteoimmunomodulation, although further in vivo demonstration should corroborate the current in vitro findings.