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Bacterial infection, peri-implant inflammation, and poor osseointegration are primary causes of failure in titanium (Ti)-based implants. Surface functionalization provides a simple and effective strategy to overcome these challenges. In this study, we developed a multifunctional coating based on porous graphdiyne (GDY) nanofilm loaded with shikonin (Skn). GDY was synthesized on Ti surfaces via a copper-catalyzed reaction to form a porous nanostructure. Following Skn loading, a composite layer of tannic acid (TA) and poly (N-isopropylacrylamide) (pNIPAM) was applied, resulting in the Ti-GDY@Skn-TP system. Upon near-infrared (NIR) irradiation, the GDY coating induced localized photothermal effects sufficient to eradicate bacteria. Concurrently, the thermo-responsive release of Skn suppressed early inflammation and promoted osseointegration by regulating macrophage polarization and inflammatory cytokine secretion. In vivo studies confirmed that Ti-GDY@Skn-TP implants effectively eliminated bacterial infections, attenuated acute inflammation, and enhanced bone tissue regeneration and implant integration. This multifunctional approach offers a promising strategy for the surface modification of Ti-based biomedical implants. [Display omitted] •Porous graphdiyne nanofilm formed on Ti via copper-catalyzed synthesis.•Shikonin-loaded GDY coating enables thermo-responsive drug release.•NIR-triggered photothermal effect achieves efficient antibacterial activity.•Shikonin modulates macrophage polarization to reduce inflammation.•Enhanced osseointegration and bone regeneration on modified Ti implants.

Mushrooms have a long history of uses for their medicinal and nutritional properties. They have been consumed by people for thousands of years. Edible mushrooms are collected in the wild or cultivated worldwide. Recently, mushroom extracts and their secondary metabolites have acquired considerable attention due to their biological effects, which include antioxidant, antimicrobial, anti-cancer, anti-inflammatory, anti-obesity, and immunomodulatory activities. Thus, in addition to phytochemists, nutritionists and consumers are now deeply interested in the phytochemical constituents of mushrooms, which provide beneficial effects to humans in terms of health promotion and reduction of disease-related risks. In recent years, scientific reports on the nutritional, phytochemical and pharmacological properties of mushroom have been overwhelming. However, the bioactive compounds and biological properties of wild edible mushrooms growing in Southeast Asian countries have been rarely described. In this review, the bioactive compounds isolated from 25 selected wild edible mushrooms growing in Southeast Asia have been reviewed, together with their biological activities. Phytoconstituents with antioxidant and antimicrobial activities have been highlighted. Several evidences indicate that mushrooms are good sources for natural antioxidants and antimicrobial agents

Hypericum androsaemum, also known as Tutsan, is a small evergreen shrub common in the Mediterranean basin where it is traditionally used as diuretic and hepatoprotective herbal drug. This plant possesses the peculiarity to produce fleshy and berry-like fruits that ripen from red to shiny black. In the present work, the chemical constituents of methanolic extracts and infusions of red and black fruits were analyzed by HPLC, and correlated with their antioxidant properties which were evaluated by the DPPH, β-Carotene/linoleic acid, and hypochlorous acid tests. In addition, the red pigment of the fruit was isolated by column chromatography and structurally elucidated by NMR. Results showed that H. androsaemum fruits contain high amounts of shikimic and chlorogenic acids, while their color was given by a tetraoxygenated-type xanthone, reported for the first time in Hypericum species. The red berries infusion gave the highest content of total phenolic compounds, DPPH, and hypochlorous acid scavenging activity, and β-carotene bleaching. Cytotoxicity of the berries extracts on three human tumor cell lines (malignant melanoma, breast adenocarcinoma, and colon carcinoma) was evaluated by MTT assay, and relevant inhibition on colon carcinoma cells (IC50 value of 8.4 μg/mL) was found. Finally, the effects of red berries extract on the immune system were evaluated by peripheral blood mononuclear cell (PBMC) proliferation assay that revealed a strong stimulation on lymphocytes at low doses (0.4-6 μg/mL).

The immunomodulatory potential of Lycium barbarum polysaccharides (LBP) is well-established, yet the intricate structure-activity relationships (SAR) underlying these effects require clarification to advance therapeutic applications. This review synthesizes current knowledge on how specific structural parameters of LBP, including molecular weight, monosaccharide composition, glycosidic linkage types, and chemical modifications influence its immunoregulatory functions. Key findings reveal a non-linear dependence of LBP’s immunomodulatory activity on molecular weight. Fractions within the medium molecular weight range (10 5 –10 6 Da) often demonstrate optimal efficacy, which is attributed to their capacity for facilitating multivalent binding to pattern recognition receptors (PRRs). Furthermore, a high content of arabinose and galactose is a critical structural determinant, with arabinogalactan-like motifs serving as key recognition elements for immune cell activation. Mechanistically, LBP orchestrates immune responses through multi-target pathways. It directly modulates macrophage polarization via the STAT1/STAT6 pathways, promotes dendritic cell maturation through NF-κB and Notch signaling, and influences T-cell differentiation. Concurrently, LBP exerts indirect immunomodulatory effects via the gut microbiota-immune axis by enriching beneficial bacteria and their immunoregulatory metabolites, such as short-chain fatty acids. Despite robust preclinical evidence, clinical translation is hampered by the heterogeneity of LBP preparations. This review underscores the necessity of standardizing LBP based on SAR insights to develop precision immunomodulators for therapeutic applications.

Polysaccharides, which can be affected by different preparations, play a crucial role in the biological function of Paecilomyces hepiali (PHPS) as a health food. To explore high-valued polysaccharides and reduce the negative influence of human involvement, a green tailorable deep eutectic solvent (DES) was applied to optimize the extraction of polysaccharides (PHPS-D), followed by the evaluation of the structural properties and immunomodulation by comparison with the hot-water method (PHPS-W). The results indicated that the best system for PHPS-D was a type of carboxylic acid-based DES consisting of choline chloride and succinic acid in the molar ratio of 1:3, with a 30% water content. The optimal condition was as follows: liquid–solid ratio of 50 mL/g, extraction temperature of 85 °C, and extraction time of 1.7 h. The actual PHPS-D yield was 12.78 ± 0.17%, which was obviously higher than that of PHPS-W. The structural characteristics suggested that PHPS-D contained more uronic acid (22.34 ± 1.38%) and glucose (40.3 ± 0.5%), with a higher molecular weight (3.26 × 105 g/mol) and longer radius of gyration (78.2 ± 3.6 nm), as well as extended chain conformation, compared with PHPS-W, and these results were confirmed by AFM and SEM. Immunomodulatory assays suggested that PHPS-D showed better performance than PHPS-W regarding pinocytic activity and the secretion of NO and pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) by activating the corresponding mRNA expression in RAW264.7 cells. This study showed that carboxylic acid-based DES could be a promising tailorable green system for acidic polysaccharide preparation and the valorization of P. hepiali in functional foods.

Fracture nonunion or delayed union presents a significant challenge in orthopedic practice. Bone healing is a complex physiological process that initiates with the modulation of inflammatory immunity and progresses through critical stages, including angiogenesis, osteogenic differentiation, and biomineralization. The intrinsic link among immune homeostasis, bacterial clearance, and osteogenic microenvironments underscores the need for an integrated therapeutic strategy. To address these challenges, we developed a multifunctional molybdenum-based polyoxometalate cluster (Mo-POM) modified with gallic acid (GA). Theoretical and experimental evidence confirms that electron transfer from GA to the Mo-POM cluster narrows the HOMO-LUMO energy gap, enhancing its multi-enzyme mimetic activity for effective reactive oxygen species (ROS) scavenging, thereby remodeling the immune microenvironment. The Mo-POM also exhibits broad-spectrum antibacterial function through synergistic disruption of bacterial membranes and biofilms. To ensure practical applicability and sustained release, the Mo-POM was encapsulated within a gellan gum/nano-hydroxyapatite (GG/nHA) hydrogel scaffold. The resulting Mo-POM@GG/nHA system effectively coordinates early immunomodulation and antibacterial activity with enhanced biomineralization in the bone regeneration process. Although polyoxometalates have demonstrated versatile biochemical properties, their application in bone regeneration remains largely unexplored. This work demonstrates that a single Mo-POM cluster acts as a core modulator, achieving the “three birds with one stone” effect by eliminating inflammation, modulating the immune microenvironment, and boosting osteogenesis, thereby providing a new avenue for designing a new class of integrated biomaterials for orthopedic applications. [Display omitted] •A multifunctional Mo-POM@GG/nHA hydrogel was developed to orchestrate immunomodulation and osteogenesis for bone repair.•Gallic acid modification enhances the multi-enzyme mimicking activity of POM nanoclusters for effective ROS scavenging.•Mo-POM nanoclusters exert broad-spectrum antibacterial activity by disrupting bacterial membranes and biofilms.•The hydrogel provides a bioactive matrix for sustained release of Mo-POM NCs and promotes osteogenic mineralization.•Mo-POM@GG/nHA hydrogel promotes regeneration through immunomodulation, antibacterial activity, and biomineralization.

The medicinal uses of saffron, the dried stigmas of L., have very long history in food coloring agent, and flavoring agent as well as traditional medicine for the treatment of several diseases. is rich in carotenoids that affect immunity. This review summarizes the putative immunoregulatory effects of saffron and its active its derivatives including crocin, crocetin and safranal. In modern studies, its active constituents including protective effects, anti-inflammatory activities and molecular mechanisms of saffron on thimmune system have been demonstrated. Furthermore, the beneficial effects of saffron on inhibition of serum levels nuclear transcription factor κB (NF-κB) p65 unit, tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ) and some interleukin (IL) such as IL-1β, IL-6, IL-12, IL-17A were reported. Furthermore, saffron has been known as the antagonist of NF-κB and the agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ). In addition, saffron down-regulates the key pro-inflammatory enzymes such as myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), phospholipase A2, and prostanoids. This review summarizes the protective roles of and its constituents against the pathogenesis of immune diseases and understanding a better management of these problems. Taken together, the main bioactive constituents of saffron may have health-promoting with important benefits in immune-related disorders. Finally, our study indicates that these bioactive constituents can affect both cellular and humoral immunity functions.

Nowadays, the oral use of probiotics is widespread. However, the safety profile with the use of live probiotics is still a matter of debate. Main risks include: Cases of systemic infections due to translocation, particularly in vulnerable patients and pediatric populations; acquisition of antibiotic resistance genes; or interference with gut colonization in neonates. To avoid these risks, there is an increasing interest in non-viable microorganisms or microbial cell extracts to be used as probiotics, mainly heat-killed (including tyndallized) probiotic bacteria (lactic acid bacteria and bifidobacteria). Heat-treated probiotic cells, cell-free supernatants, and purified key components are able to confer beneficial effects, mainly immunomodulatory effects, protection against enteropathogens, and maintenance of intestinal barrier integrity. At the clinical level, products containing tyndallized probiotic strains have had a role in gastrointestinal diseases, including bloating and infantile coli—in combination with mucosal protectors—and diarrhea. Heat-inactivated probiotics could also have a role in the management of dermatological or respiratory allergic diseases. The reviewed data indicate that heat-killed bacteria or their fractions or purified components have key probiotic effects, with advantages versus live probiotics (mainly their safety profile), positioning them as interesting strategies for the management of common prevalent conditions in a wide variety of patients´ characteristics.

The need to search for new, alternative treatments for various diseases has prompted scientists and physicians to focus their attention on regenerative medicine and broadly understood cell therapies. Currently, stem cells are being investigated for their potentially widespread use in therapies for many untreatable diseases. Nowadays modern treatment strategies willingly use mesenchymal stem cells (MSCs) derived from different sources. Researchers are increasingly aware of the nature of MSCs and new possibilities for their use. Due to their properties, especially their ability to self-regenerate, differentiate into several cell lineages and participate in immunomodulation, MSCs have become a promising tool in developing modern and efficient future treatment strategies. The great potential and availability of MSCs allow for their various clinical applications in the treatment of many incurable diseases. In addition to their many advantages and benefits, there are still questions about the use of MSCs. What are the mechanisms of action of MSCs? How do they reach their destination? Is the clinical use of MSCs safe? These are the main questions that arise regarding MSCs when they are considered as therapeutic tools. The diversity of MSCs, their different clinical applications, and their many traits that have not yet been thoroughly investigated are sources of discussions and controversial opinions about these cells. Here, we reviewed the current knowledge about MSCs in terms of their therapeutic potential, clinical effects and safety in clinical applications.

The antimalarial hydroxychloroquine (HCQ) has demonstrated several crucial properties for the treatment of systemic lupus erythematosus (SLE). Herein, we reviewed the main HCQ pharmacologic features, detailed its mechanism of action, and summarized the existing guidelines and recommendations for HCQ use in rheumatology with a systematic literature search for the randomized controlled trials focused on lupus. HCQ has been shown to decrease SLE activity, especially in mild and moderate disease, to prevent disease flare and to lower the long-term glucocorticoid need. The numerous benefits of HCQ are extended to pregnancy and breastfeeding period. Based on cohort studies, antithrombotic and metabolic HCQ’s effects were shown, including lipid-lowering properties, which might contribute to an improved cardiovascular risk. Moreover, early HCQ use in antinuclear antibodies positive individuals might delay the progression to SLE. Finally, HCQ has a significant favorable impact on long-term outcomes such as damage accrual and mortality in SLE. Based on these multiple benefits, HCQ is now the mainstay long-term treatment in SLE, recommended by current guidelines in all patients unless contraindications or side effects. The daily dose associated with the best compromise between efficacy and safety is matter of debate. The concern regarding retinal toxicity rather than proper efficacy data is the one that dictated the daily dosage of ⩽5 mg/kg/day actual body weight currently agreed upon.