A microenvironment responsive polyetheretherketone implant with antibacterial and osteoimmunomodulatory properties facilitates osseointegration.

Failure of intraosseous prostheses is primarily attributed to implant loosening and infections. Current primary therapeutic modalities, such as antibiotics and local debridement, not only face challenges in thoroughly eliminating obstinate adhered bacteria but also encounter difficulties in ameliorating undue inflammatory reactions and regenerating impaired peri-implant bone tissues. Polyetheretherketone (PEEK) has excellent mechanical and physicochemical characteristics and has been used extensively as a medical biomaterial. However, the limited bactericidal and osseointegrative activities of bioinert PEEK restrict its clinical application. Herein, a microenvironment responsive coating with immobilised immunomodulatory magnesium ions (Mg2+) and disinfectant cerium oxide nanoparticles (CNPs) is designed via ion coordination mediated by polydopamine (PDA) and electrospinning based on collagen structure-bionic silk fibroin (SF). By utilising the pH responsiveness of SF, CNPs exhibit potent antibacterial effects in an acidic environment (pH 5.0) caused by local bacterial infection. Due to the chelation interaction with PDA and the constraint of SF, Mg2+ is slowly released, ameliorating the local immune microenvironment and boosting osteogenesis by upregulating M2 phenotype macrophages. Bioinformatics analysis indicates that the inflammation is suppressed via the NF-κB signaling pathway. Overall, this SF-based coating maximizes the synergistic effect of CNPs and Mg2+, offering enhanced antibacterial and osteoimmunomodulatory bioactivity for successful implantation.

Structure analysis and immunomodulatory activity of novel oligosaccharide from Nicotiana tabacum roots.

A novel oligosaccharide (NTRP60-W-2) with an average molecular weight of 1377 Da was isolated and purified from Nicotiana tabacum roots. Its structural characteristics and immunomodulatory properties were investigated. Structural analysis revealed that NTRP60-W-2 was composed exclusively of glucose, featuring →1)-α-D-Glcp-(6→ backbone. Immunological assays demonstrated that NTRP60-W-2 significantly enhanced cell viability, nitric oxide production and cytokine secretion (IL-6 and TNF-α) in RAW264.7 cells. These findings provide a foundation for further exploration of Nicotiana tabacum carbohydrates and their potential biological activities.

Harnessing the Anti-Inflammatory Properties of Polyphenols in the Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) encompasses a spectrum of chronic inflammatory conditions affecting the gastrointestinal tract, notably ulcerative colitis (UC) and Crohn's disease (CD). Both UC and CD result from the interplay between genetic and environmental factors that trigger an exacerbated immune response against gut microorganisms, leading to non-resolving inflammatory damage in the mucosa of specific zones in the intestine. Despite extensive research, current treatments often entail invasive interventions with considerable adverse effects on patient well-being. Consequently, there is a pressing need to find alternative and complementary therapeutic strategies aimed at ameliorating chronic inflammation and restoring intestinal barrier integrity. Polyphenols are plant-based compounds formed naturally or as semi-synthetic/synthetic derivatives with proven health-promoting effects and translational applications in a broad spectrum of chronic diseases. Preclinical models of IBD largely support the efficacy of a broad variety of polyphenols due to their well-documented antioxidant and modulatory properties on the immune system and gut microbiota. Likewise, a growing number of studies using distinct types of polyphenols are being conducted in humans, although more efforts are still warranted. In the present review, the main polyphenols investigated in vitro and in vivo models of IBD will be summarized, as well as the available trials or observational data accessible in humans. Finally, the role of polyphenols in the clinical context of IBDs, along with the main problematics regarding their translational issues and concerns will be discussed, including bioavailability, their inclusion in healthy dietary patterns and foods, interaction with other drugs, and other important points to be addressed by future research.

Exploring the therapeutic potential of polysaccharide from Portulaca oleracea L.: A review of phytochemistry and immunomodulatory effect.

Portulaca oleracea L., a plant with both edible and medicinal properties, is traditionally valued for its diuretic, antipyretic, antiseptic, antispasmodic, and anthelmintic functions in folk medicine. P. oleracea polysaccharide (POP), a pivotal bioactive component, has various biological activities. Notably, their immunomodulatory capabilities have emerged as a significant area of research. The extraction, purification, monosaccharide composition, structure characterization, and biological activity of POP have been extensively investigated to identify the active components and to clarify their pharmacological actions and underlying molecular mechanisms. It aims to delineate the pharmacological mechanisms and molecular pathways associated with these polysaccharides, thereby underscoring their therapeutic promise and nutritional significance. Furthermore, the review critically examines the current research landscape of POP, identifying gaps and proposing innovative perspectives to enrich the scientific discourse surrounding these bioactive compounds.

Structural characterization and immunomodulatory activity of polysaccharides from the lateral roots of Aconitum carmichaelii.

Two polysaccharides, named FPS1-1 and FPS1-2, were separated from the neutral polysaccharides of the lateral roots of Aconitum carmichaelii, a widely used traditional Chinese medicine (Fuzi in Chinese). The monosaccharide composition analysis indicated that both FPS1-1 and FPS1-2 were glucans. However, further physicochemical analysis of FPS1-1 and FPS1-2 revealed distinct properties between the two glucans. FPS1-1 had a molecular weight (Mw) of 106.23 kDa with a spherical conformation, while FPS1-2 had a lower Mw of 19.23 kDa with a random coil conformation. The structure of FPS1-2 was further determined as a glucan whose backbone structure was composed of →4)-α-D-Glcp-(1→. The immunological activities of two polysaccharides were evaluated by a cyclophosphamide (CTX)-induced immunodeficiency model in mice. The result showed that FPS1-2 could restore CTX-induced immunosuppression by modulating CD4+ T cells differentiation and promoting cytokine secretion. Notably, FPS1-2 could modulate the colonic short-chain fatty acid (SCFA) levels and reverse the gut microbial dysbiosis induced by CTX. These findings reveal the potential benefits of Fuzi polysaccharides and provide evidences for developing immunologically functional products from Fuzi polysaccharides.

MBG/BSA Bone Grafts Immunomodulate Bone Regeneration by Releasing Bioactive Ions in Inflammatory Bone Defects.

Since the diseases that cause bone defects are mostly inflammatory diseases, the current bone grafts are unable to effectively regulate osteoimmune activity, leading to the impaired osteogenesis and unfavorable bone regeneration. In this study, inspired by bone composition, biomimetic mesoporous bioactive glass nanoparticle (MBG)/bovine serum albumin (BSA) bone grafts are designed for inflammatory bone defects. Systematically, MBG/BSA bone grafts are evaluated for characterization, bioactivity, anti-inflammatory, antioxidant activity, and osteogenic activity. MBG/BSA bone grafts are proved to be biocompatible and can release bioactive ions including calcium and silicon in a sustained manner. Furthermore, MBG/BSA reprograms the macrophage phenotype toward anti-inflammation that is beneficial for bone regeneration. The antioxidative activity is also validated under inflammation and the mechanism may be via the interleukin-4 (IL-4)/Signal transducer and activator of transcription 6 (STAT6) pathway. The osteogenic differentiation and mineralization are also facilitated due to the improved immunoregulation of MBG/BSA. Overall, this work suggests that the MBG/BSA bone grafts with improved immunomodulatory properties are an ideal material for inflammatory bone regeneration application.

Long-Term Outcomes of Pediatric Pars Planitis: Retrospective Cohort from a Single Tertiary Center in Turkey.

PURPOSE: To retrospectively analyze long-term outcomes of pediatric pars planitis (PP). METHODS: PP was defined as vitreal inflammation with snowbank or snowball formation in the absence of a related disease. Eighty-five eyes of 44 patients were included in this study. Demographic and clinical characteristics were obtained from medical records. RESULTS: Approximately 70% of the patients were males; the mean patient age was 10.4 ± 3.6 years at presentation, and the mean follow-up time was 42.8 ± 27.9 months. At presentation, the mean best corrected visual acuity (BCVA, logMAR) was 0.17 ± 0.27 in the right eyes and 0.27 ± 0.33 in the left eyes. Common symptoms included blurry vision (29 eyes, 65%), redness (17, 38%), pain (8, 18%), and floaters (5, 11%). Sight-threatening complications included optic disc edema/hyperemia (26, 30%), cataracts (16, 18%), macular edema (16, 18%), and glaucoma (15, 17%). All 38 patients who initially required systemic treatment received corticosteroids. During the follow-up, 24 patients were treated with azathioprine, 20 with methotrexate, 11 with cyclosporine, 20 with adalimumab, and 8 with infliximab. At the final examination, the mean BCVA of the right and left eyes improved significantly (0.08 ± 0.23 and 0.06 ± 0.17, p = 0.006 and p < 0.001, respectively). The severities of vitritis, anterior chamber inflammation, snowbank/snowball formation, and endotheliitis decreased (all p < 0.001). Thirty-one patients remained on systemic treatment, with only four patients still receiving corticosteroids. No life-threatening adverse effects were reported. CONCLUSION: Despite pediatric PP's mild course, severe vision-threatening complications can occur. Immunomodulatory or biologic agents are important for controlling inflammation and tapering corticosteroids. Further research could enhance understanding of optimal treatments.

Hylotelephium telephium (L) H. Ohba leaves juice improves herpetic lesions: new findings from in vitro investigations.

The efficacy of Hylotelephium telephium (L.) H. Ohba (better known with its botanical synonym Sedum telephium L.) fresh leaf juice in the treatment of Herpes labialis wounds has been reported in traditional medicine in particular in Central regions of Italy; however, scientific insights are missing and the mechanism of action is not well understood. Aim of this study was to investigate the biological properties of S. telephium that underlie its ability to heal herpetic lesions. S. telephium fresh leaf juice (STJ) was analysed to obtain phytochemical information and tested in vitro to evaluate its antiviral activity against HSV-1 in Vero cells, then, according to computational predictions, immunomodulatory properties of STJ in human lympho-monocytes (PBMC), as well as its effect on cell viability in human keratinocytes (HaCaT cells), were also evaluated. Our results, at least in part, may explain the improvement of herpetic lesions empirically observed in patients treated with STJ: such improvement was not related to direct anti-viral effect of the juice but to its experimentally confirmed activity as cell viability booster and immunomodulatory agent.

Favorable Prognosis in Patients With Multiple Myeloma and Lenalidomide-Induced Skin Rash: A Multicenter Retrospective Study.

Although lenalidomide is an essential treatment for multiple myeloma (MM), skin rashes are a common adverse event. This retrospective study aimed to examine the association between skin rash development during lenalidomide treatment and the prognosis of relapsed/refractory MM. All patients who received lenalidomide at 10 hospitals between July 2009 and December 2015 were included in the study. The relationship of skin rash development with disease progression and survival was evaluated. Multivariate analysis was performed to identify factors affecting disease progression or survival, including skin rash. Of the 245 patients analyzed, 70 developed skin rashes. The median progression-free survival (PFS) of patients with skin rashes was 22.4 months, whereas the median PFS for patients who did not develop skin rashes was 10.5 months (p = 0.003). The median overall survival for patients with and without skin rash was 42.6 and 24.6 months, respectively (p = 0.013). Multivariate regression analysis showed that skin rash was an independent prognostic factor for PFS (p = 0.009). In this study, patients with skin rashes during lenalidomide treatment had significantly better PFS than those without such symptoms, indicating that lenalidomide-associated skin rashes may be a predictor of clinical outcomes in patients with MM.

Unveiling Stingless Bee Honey Anti-inflammatory Potential Through the Polarization of LPS-induced J774 Macrophages.

Macrophages play an important role during the inflammatory process. These cells can adopt either the pro- or anti-inflammatory phenotypes. While stingless bee honeys have demonstrated evidence of anti-inflammatory potential, their capacity to induce a shift from a pro-inflammatory state to an inflammation-resolution state has not been thoroughly investigated. In this study, the anti-inflammatory activity of two stingless bees (Scaptotrigona bicunctata-honey A and Melipona quadriasciata-honey G) honeys in J774 macrophages induced by LPS was evaluated. Both honeys exhibited non-cytotoxic effects and reduced nitrite and IL-4 levels. However, only honey G increased the levels of the anti-inflammatory cytokine IL-13, by 163.1 ± 14.8% (p < 0.05) and was further investigated for its immunomodulatory effect. This honey reduced the expression of TLR4 by 59.3 ± 3.5% (p < 0.001) and increased the mannose receptor levels by 67.3 ± 2.4% (p < 0.001). Moreover, it increased the phagocytic activity by 25.0 ± 7.7% (p < 0.01) and decreased the death of the macrophages by 32.1 ± 1.7% (p < 0.001). Collectively, these findings highlight stingless bee honey from Melipona quadriasciata bee has an important immunomodulatory effect, as it reduces the markers of the pro-inflammatory state of J774 cells and increases the markers of resolution or anti-inflammatory responses.

Immunomodulatory effect of Tityus sp. in mononuclear cells extracted from the blood of rheumatoid arthritis patients.

Background: Pathophysiological mechanisms of rheumatoid arthritis arise because of a proinflammatory environment, generated by the interaction of autoreactive lymphocytes and proinflammatory mediators. Current strategies to mitigate the progression of the disease produce adverse effects, so there is a need for new therapeutic strategies and molecular targets to treat this disease. In this context, evidence suggests that scorpion venoms could modulate the immune response and some important cellular mechanisms of pharmacological interest. To evaluate the immunomodulatory effect of the venom of Tityus sp. (a possible new species close to Tityus metuendus) peripheral blood mononuclear cells of women diagnosed with RA were compared to cells of a control group. Methods: A case-control study was conducted with a sample of 10 women with a confirmed diagnosis of RA and controls matched by sex and age. The cytotoxicity of the venom was evaluated to find sublethal concentrations of the venom, and subsequently, their immunomodulatory capacity in terms of percentage of proliferation, cell activation, and cytokines production. Results: the venom of Tityus sp. produced a decrease in the percentage of proliferation in the CD3+, CD3+CD4+, and CD3+CD8+ cell subpopulations of RA patients and healthy controls, at concentrations of 252 and 126 µg/mL. However, the venom did not induce significant differences in the percentage of cell activation markers. The venom caused a decrease in IL-10 at a concentration of 252 µg/mL compared to untreated cells from patients and controls. The remaining cytokines did not show significant differences. Conclusion: the venom of Tityus sp. is a potential source of molecules with immunomodulatory ability in CD4 and CD8 T lymphocytes. This result directs venom characterization studies to identify pharmacological targets with immunomodulatory capacity in T lymphocytes to enhance research in the treatment of autoimmune disorders such as RA.

The Structure Characterization of Polysaccharides from Codonopsis pilosula and the Structure-activity Relationship with Immune-regulation on THP-1 Cells.

In recent years, polysaccharides from Codonopsis pilosula (CPs) have received increasing attention for their excellent behaviors in immune-regulation. However, the relationship between the structure and immunomodulatory activity has rarely been reported. In this work, four fractions purified from crude CPs (CPW, CPS0.2, CPS0.5, CPS1) by chromatographic column separation were explored with both structure and immunomodulatory effects by THP-1 cells. The results showed that the monosaccharide composition, chain conformation, molecular weight (Mw) and aggregated state of CPs were different. At the same time, the immunomodulatory effects of CPs were also varied depend on structure differences, as indicated by the released cytokines of TNF-α and IL-1ß by LPS-induced THP-1 cells. Finally, we summarized and concluded that the spherical structure and smaller particle size of CPs were the key factors attributed to better immune-enhancing effects. The results showed that the monosaccharide combination differences of polysaccharides might lead to anti-inflammatory or pro-inflammatory activity. Moreover, the higher percentage of glucose, the relatively large particle size, as well as the extended chain conformation of CPs might be the key factors attributed to better immune-enhancing effects. This study aims to provide a theoretical basis for establishing the structure-activity relationship of CPs.

Immunohistochemical Expression of Immune Regulatory Proteins in Interface Dermatoses.

Cutaneous immune-related adverse events (irAEs) of immunotherapies, such as anti-programmed cell death protein-1 (PD-1), suggest that immune checkpoint factors may contribute to the pathobiology of lichenoid interface dermatitis in immunotherapy-naïve patients. Our study aimed to describe innate and adaptive immune markers via immunohistochemical (IHC) staining of lichenoid interface dermatoses. We studied the staining patterns of PD-L1, STING, IL-36 gamma, CD8, PD-1, and LAG-3 in five interface dermatoses: oral lichen planus (LP) (n = 10), cutaneous LP (n = 10), chronic cutaneous lupus erythematosus (CLE) (n = 11), erythema multiforme (EM) (n = 11), and toxic epidermal necrolysis (TEN) (n = 13), by immunohistochemistry (IHC) analysis. Expression was evaluated semi-quantitively according to the percentage of keratinocytes and dermal lymphocytes stained compared to keratinocytes and resident pericapillary lymphocytes in normal human skin. All interface dermatoses evaluated showed increased expression of PD-L1 on keratinocytes and LAG-3 in lymphocytes. STING was increased on the keratinocytes of most specimens. Expression of IL-36 gamma, in basal layer keratinocytes was more extensive in oral LP and cutaneous LP and varied in CLE, EM, and TEN. Lymphocytic infiltration expressing PD-1 was elevated in oral LP, cutaneous LP, and CLE. Current thinking is that interface dermatitis is the result of a cell-mediated immune reaction involving cytotoxic CD8+ T-cell-mediated apoptosis of keratinocytes. The findings of this study suggest that in addition to cell-mediated immunity, innate immune factors may contribute to pathobiology.

Immunomodulatory effects and multi-omics analysis of Codonopsis Pilosula Extract in septic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Codonopsis Pilosula (CP), as a well-known traditional Chinese medicine (TCM) with medicinal and edible herb, is one of the most representative tonic Chinese herbal medicine. It has been widely used for regulating immune function with hardly any adverse effects in clinical practice. AIM OF THE STUDY: This study aimed to elucidate the immunomodulatory effect and to explore probable mechanism of Codonopsis Pilosula Extract (CPE) in septic rats. MATERIALS AND METHODS: The model of septic rat was established by cecal ligation and perforation (CLP). The thymus index, spleen index and cerebral index were calculated. Histological changes were observed by Hematoxylin-eosin (HE). The positive expression of CD4+ T cells was determined in the thymus and spleen by immunohistochemical (IHC). The expression level of 24 h CD4 was corroborated by real-time quantitative polymerase chain reaction (RT-QPCR). Infectious factors, immune factors and inflammatory factors were determined by enzyme-linked immunosorbent assay (ELISA). Blood cells were detected by automatic biochemical analyzer. The metabolite changes and gene expression levels, the potential targets and pathways of CPE in regulating immune function of thymus were analyzed by integrative analysis of transcriptomic and metabolomic methods. RESULTS: High dose of CPE increased the thymus index and spleen index of septic rats at different stages, and the brain index at different stages could be increased at medium dose and high dose. Medium and high doses of CPE reduced the pathological changes of thymus, spleen and brain tissue. CPE promoted the expression levels of CD4 in the thymus and spleen. CPE improved the levels of red blood cells (RBC), lymphocytes (LYM) and hemoglobin (HGB), and decreased the levels of neutrophils (NEUT), NLR (NEUT/LYM) and PLR (PLT/LYM). CPE dynamically regulated the levels of white blood cells (WBC) and PLT (platelet). CPE dynamically regulated the expression levels of infectious factors, immune factors, and inflammatory factors related to disease severity. CONCLUSION: CPE has the ability to dynamically modulate the expression levels of infectious factors, immune factors, and inflammatory factors related to disease severity, and alleviate the damages of immune organs. The research has provided a global view of the integration of metabolomics and transcriptomics to elucidate the immunomodulatory effects and mechanisms of CPE. CPE could affect a series of biological processes in glycerophospholipid metabolism by interfering with the B cell receptor (BCR) signaling pathway in the thymus, to maintain immune homeostasis of septic rats on the whole, especially humoral immunity.

Recent advancements in cGAS-STING activation, tumor immune evasion, and therapeutic implications.

The cGAS-STING signaling pathway is indeed a pivotal component of the immune system and serve as a crucial link between innate and adaptive immune responses. STING is involved in the cellular response to pathogen invasion and DNA damage, and which has important consequences for host defense mechanisms and cancer regulation. Ongoing research aiming to modulate the cGAS-STING pathway for improved clinical outcomes in cancer and autoimmune diseases is underway. Indeed, the interaction between the cGAS-STING pathway and immune evasion mechanisms is a complex and critical aspect of cancer biology. Pathogens and various host factors can exploit this pathway to reduce the effectiveness of cancer therapies, particularly immunotherapies. Thus, immunotherapies or combination therapies may assist in overcoming the immune suppression and improving clinical outcomes. This review explores recent advancements in understanding the cGAS-STING signaling pathway, with particular emphasis on its activation mechanisms and role in tumor immune evasion. The dual role of the pathway in boosting immune responses while simultaneously enabling tumors to evade the immune system makes it a crucial target for innovative cancer treatment approaches.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 2 Given name: [Md Mazedul] Last name [Islam], Author 3 Given name: [Mst Rubaiat Nazneen] Last name [Akhand] and Author 5 Given name: [Md Rashedunnabi] Last name [Akanda]. Also, kindly confirm the details in the metadata are correct.AQ1: Here Author 4 given name: [Byung-Yong] Last name [Park] is missing. Metadata are correct.

Longitudinal safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine in children aged 4-11 years with juvenile-onset autoimmune inflammatory rheumatic diseases: A prospective multicenter study.

This prospective, longitudinal, multicenter study assessed the safety and efficacy of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine among children 4-11 years-old with autoimmune inflammatory rheumatologic disease (AIIRD), compared to healthy controls. The study was conducted from 11/2021-12/2022 at 4 tertiary pediatric rheumatology units in Israel. Participants received at least 2 vaccine doses. Safety analysis included adverse events and disease activity measures. Efficacy was assessed by COVID-19 infection rates. Immunogenicity was evaluated in a subset of participants using anti- receptor binding domain antibody titers. Thirty-one children with AIIRD and 45 immunocompetent controls with similar baseline characteristics were included. Safety profile was favorable, with mild or no adverse events reported. The adverse event rates were similar in the AIIRD and control groups after the first (27 (60 %) vs. 14 (45.2 %), p = 0.2977) and the second vaccine doses (22 (49.0 %) vs. 18 (58.1 %), p = 0.5799), respectively. AIIRD activity remained stable and low after vaccination. Breakthrough COVID-19 infection rates were similar between groups, with 15 (48.4 %) in the AIIRD vs. 25 (55.6 %) in the control group (p = 0.7029). All reported COVID-19 infections in the AIIRD group and 18 (72 %) in the control group were symptomatic (p = 0.033), although symptoms were generally mild, with no severe disease. The safety of the BNT162b2 COVID-19 vaccine was excellent in children ages 4-11 years with AIIRD and healthy controls. Efficacy between groups was similar.

Immunostimulatory Activity of a Mixture of Platycodon grandiflorum, Pyrus serotine, Chaenomeles sinensis, and Raphanus sativus in RAW264.7 Macrophages.

In this study, a mixture of Platycodon grandiflorum, Pyrus serotina, Chaenomeles sinensis, and Raphanus sativus (PPCRE) was investigated for their immuno-enhancing effects, as well as the molecular mechanism of PPCRE in RAW264.7 cells. PPCRE dramatically increased nitric oxide (NO) and prostaglandin E2 (PGE2) generation depending on the concentration while exhibiting no cytotoxicity. PPCRE markedly upregulated the mRNA and protein expression of immune-related cytotoxic factors such as cyclooxygenase (COX)-1, COX-2, and inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha (TNF-α), as well as the mRNA level of IL-4. PPCRE increased the mitogen-activated protein kinase (MAPK) signaling pathway by upregulating the phosphorylation of extracellular signal-regulated kinase (ERK), stress-activated protein kinase/Jun N-terminal-kinase (SAPK/JNK), and p38. Furthermore, PPCRE considerably activated the nuclear factor kappa B (NF-κB) signaling pathway by increasing phosphorylation of NF-κB-p65. PPCRE-stimulated RAW264.7 cells increased macrophage phagocytic capacity. In conclusion, our study found that PPCRE improved immune function by modulating inflammatory mediators and regulating the MAPK and NF-κB pathway of signaling in macrophages.

Biocompatible Poly(ε-Caprolactone) Nanocapsules Enhance the Bioavailability, Antibacterial, and Immunomodulatory Activities of Curcumin.

Curcumin (Cur), the primary curcuminoid found in Curcuma longa L., has garnered significant attention for its potential anti-inflammatory and antibacterial properties. However, its hydrophobic nature significantly limits its bioavailability. Additionally, adipose-derived stem cells (ADSCs) possess immunomodulatory properties, making them useful for treating inflammatory and autoimmune conditions. This study aims to verify the efficacy of poly(ε-caprolactone) nanocapsules (NCs) in improving Cur's bioavailability, antibacterial, and immunomodulatory activities. The Cur-loaded nanocapsules (Cur-NCs) were characterized for their physicochemical properties (particle size, polydispersity index, Zeta potential, and encapsulation efficiency) and stability over time. A digestion test simulated the behavior of Cur-NCs in the gastrointestinal tract. Micellar phase analyses evaluated the Cur-NCs' bioaccessibility. The antibacterial activity of free Cur, NCs, and Cur-NCs against various Gram-positive and Gram-negative strains was determined using the microdilution method. ADSC viability, treated with Cur-NCs and Cur-NCs in the presence or absence of lipopolysaccharide, was analyzed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay. Additionally, ADSC survival was assessed through the Muse apoptotic assay. The expression of both pro-inflammatory (interleukin-1ß and tumor necrosis factor-α) and anti-inflammatory (IL-10 and transforming growth factor-ß) cytokines on ADSCs was evaluated by real-time polymerase chain reaction. The results demonstrated high stability post-gastric digestion of Cur-NCs and elevated bioaccessibility of Cur post-intestinal digestion. Moreover, Cur-NCs exhibited antibacterial activity against Escherichia coli without affecting Lactobacillus growth. No significant changes in the viability and survival of ADSCs were observed under the experimental conditions. Finally, Cur-NCs modulated the expression of both pro- and anti-inflammatory cytokines in ADSCs exposed to inflammatory stimuli. Collectively, these findings highlight the potential of Cur-NCs to enhance Cur's bioavailability and therapeutic efficacy, particularly in cell-based treatments for inflammatory diseases and intestinal dysbiosis.

The synergistic immunomodulatory activity of Lycium barbarum glycopeptide and isochlorogenic acid A on RAW264.7 cells.

BACKGROUND: Regulation of the immune system to maintain homeostasis in the organism has become a focus of research, and the synergistic effect of multi-component complexes will effectively improve the immunomodulatory activity. The present study aimed to investigate the interaction and synergistic immunomodulatory activity of isochlorogenic acid A (IAA) and Lycium barbarum glycopeptide (LbGp). RESULTS: The results obtained indicated that non-covalent intermolecular interactions were employed to form the LbGp-IAA complex, with a binding ratio of 135.15 mg g-1. The formation of LbGp-IAA complex altered the conformation of LbGp, and IAA was mainly bound to LbGp by van der Waals forces and hydrogen bonds. In addition, LbGp-IAA promoted the proliferation of RAW264.7 cells. The IAA and LbGp interaction had a synergistic effect on the promotion of phagocytosis and the expression of nitric oxide, tumor necrosis faction-α and interleukin-1ß, which improved the immunomodulatory effect of LbGp. Furthermore, the combination of LbGp and IAA synergistically inhibited lipopolysaccharide-induced inflammatory response. CONCLUSION: In summary, the binding of IAA enhanced the immunomodulatory activity of LbGp and coordinated the immune response, and did not trigger an inflammatory response, which was potentially attributed to the alteration of spatial structure of LbGp through the binding of IAA. The results provide new perspectives for the study of glycopeptide-polyphenol interactions. © 2024 Society of Chemical Industry.

Serum inflammatory biomarkers associated with disease severity and response to dupilumab treatment in bullous pemphigoid: A cluster analysis.

BACKGROUND: Dupilumab, a novel therapy targeting the T helper (Th) 2-mediated inflammation, is showing clinical benefits in treating bullous pemphigoid (BP). However, limited research investigated the serum biomarkers that reflect the inflammation alterations throughout the disease course. OBJECTIVES: To explore the changes of the serum inflammatory biomarkers under dupilumab therapy in BP and establish their correlations with disease severity and clinical outcomes. METHODS: This exploratory study evaluated serum samples from 40 patients with BP at baseline, 30 of these patients following 16-week dupilumab therapy, and 20 senior healthy controls. Serum levels of 29 cytokines and chemokines were quantified using the Magnetic Luminex Assay. RESULTS: Two distinct clusters based on serum inflammatory profiles were identified. The first cluster, characterized by elevated levels of inflammatory activation, exhibited worse disease severity and poorer remission outcomes. Following the 16-week dupilumab therapy regimen, a significant suppression of Th2-mediated inflammation in the serum was observed, alongside a relative upregulation of Th1 responses. Patients treated with adjuvant systemic steroids exhibited an enhanced suppression of B cell activating factor compared to those receiving dupilumab alone. Significant correlations were unveiled between Th2 biomarkers and clinical scores, eosinophil counts, and anti-BP180 immunoglobulin G levels. Baseline levels of CCL18, Periostin, interleukin (IL)-6, and IL-16 constitute an optimal combination to distinguish between inflammatory clusters. CONCLUSIONS: Cluster analysis of serum inflammatory biomarkers provided novel insights into the heterogeneity of the inflammation profiles in BP. Baseline levels of CCL18, Periostin, IL-6, IL-16 emerged as effective predictors for disease severity and therapy response to dupilumab.