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Phyllanthus emblica L. offers promising therapeutic potential for inflammatory diseases. This study revealed the molecular structure of a homogeneous polysaccharide purified from Phyllanthus emblica L. (PEP-1) and evaluated its anti-inflammatory effects on ulcerative colitis (UC) in mice. In the in vivo experiment, administered in varying dosages to dextran sulfate sodium (DSS)-induced UC models, PEP-1 significantly alleviated colonic symptoms, histological damages and reshaped the gut microbiota. Notably, it adjusted the Firmicutes/Bacteroidetes ratio and reduced pro-inflammatory species, closely aligning with shifts in the fecal metabolites and metabolic pathways such as the metabolism of pyrimidine, beta-alanine, and purine. These findings underscore the potential of PEP-1 as a therapeutic agent for UC, providing insights into the mechanisms through gut microbiota and metabolic modulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cinnamic acids are aromatic acids primarily found in plants and plant-derived food. Phenolic cinnamic acids, with one or more hydroxyl groups in the aromatic ring, often contribute to the biological activities attributed to these compounds. The presence of hydroxyl groups and a carboxyl group makes cinnamic acids very hydrophilic, preventing them from crossing biological membranes and exerting their biological activities. To alleviate this condition, a panel of synthetic modifications have been made leading to a diverse set of phenolic cinnamic structures. In this review, an overview of the natural phenolic cinnamic acid derivatives and their plant sources (more than 200) is described. The synthetic approaches to obtain the referred derivatives (more than 200) namely esters and amides are reviewed. Further, their anti-inflammatory activity (more than 70 compounds) is scrutinized. Finally, future directions will be indicated to translate the research on phenolic cinnamic derivatives into potentially effective anti-inflammatory drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

This study investigated the changes in phytochemical composition and inflammatory response of crude papaya (Carica papaya L.) seed oil (CPO) and its refined forms (degummed, PDG; deacidified, PDA; decolorized, PDC; deodorized, PDO). Oils were analyzed for their phytochemical composition, oil quality parameters, antioxidant activity, and their inflammatory response in LPS-stimulated THP-1 macrophages. At higher refining degrees, particularly after deacidification, the contents of phytochemicals (sterols, tocopherols, and polyphenols) decreased while oxidation products increased. Both CPO (0.1-1.0 mg/mL) and PDG reduced the secretion and mRNA expression of LPS-stimulated inflammatory cytokines and mediators and also blocked the activation of the NF-κB pathway. PDA, PDC, and PDO showed low anti-inflammatory or even pro-inflammatory activity. Correlation analysis showed that 4 polyphenols and 2 phytosterols were responsible for the oil's anti-inflammatory effects. These findings indicated that moderate refining is suggested for papaya seed oil processing for retaining bioactive ingredients and anti-inflammatory ability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Opantimycin A, a rare antimycin-class antibiotic without the macrolide core, was isolated from Streptomyces sp. RK88-1355 in 2017. In this study, we explored the total synthesis and stereochemical assignment of opantimycin A. The synthesis of all potential diastereomers has been accomplished via traceless Staudinger ligation. A comparison of the spectroscopic data of the synthesized compounds with that reported for the natural product confirmed that the absolute configuration of the natural product was (14 S ,17 R ,21 R ). Two analogous compounds were prepared, where the Dhb (( Z )-dehydrobutyrine) moiety was replaced with Dha (dehydroalanine) or ΔVal moieties, respectively. The inhibitory activities of these synthetic compounds against the production of the anti-inflammatory cytokine IL-6 were evaluated, and two potential candidates for further development as anti-inflammatory agents were identified.

Fructus Choerospondiatis (FC) has been utilized in Mongolian medicine for the treatment of many diseases. This investigation assessed the coloration, five active components, total phenolic and flavonol contents, as well as the antioxidant and antibacterial properties of different parts of FC from eight cultivars, and the optimal cultivar was identified to determine the anti-inflammatory capacity of all parts. The findings revealed that L* and b* values of the dried peel powder were the highest and the a* value of whole fruit powder was the highest. The concentrations of gallic acid, catechin, epicatechin, total phenols, and total flavonoids exhibited a positive correlation with antioxidant activity. A comprehensive analysis revealed that the peel contained a greater abundance of active compounds and exhibited stronger antioxidant and antibacterial properties compared to other parts. RPNO.1 can be used as the source of high-quality FC for clinical application. In vivo anti-inflammatory experiments indicated that both the flesh and peel of RPNO.1 displayed the highest anti-inflammatory effect. This research not only addressed the gap in studies regarding FC ' s anti-inflammatory properties but also proved that the peel of FC, which was often discarded, had utilization value and could be used as a medicinal herb., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Bitter taste receptors (TAS2Rs), a subfamily of G-protein coupled receptors (GPCRs) expressed orally and extraorally, elicit signaling in response to a large set of tastants. Among 25 functional TAS2Rs encoded in the human genome, TAS2R14 is the most promiscuous, and responds to hundreds of chemically diverse ligands. Here we present the cryo-electron microscopy (cryo-EM) structure of the human TAS2R14 in complex with its signaling partner gustducin, and bound to flufenamic acid (FFA), a clinically approved nonsteroidal anti-inflammatory drug. The structure reveals an unusual binding mode, where two copies of FFA are bound at distinct pockets: one at the canonical receptor site within the trans-membrane bundle, and the other in the intracellular facet, bridging the receptor with gustducin. Together with a pocket-specific BRET-based ligand binding assay, these results illuminate bitter taste signaling and provide tools for a site-targeted compound design., Competing Interests: Competing interests The authors declare no competing interests, (© 2024. The Author(s).)

Background: The global demographic shift towards an aging population is generating a rise in neurodegenerative conditions, with Alzheimer's disease (AD) as the most prominent problem. In this landscape, the use of natural supplements has garnered attention for their potential in dementia prevention. Curcumin (Cur), derived from Curcuma longa, has demonstrated promising pharmacological effects against AD by reducing the levels of inflammatory mediators. However, its clinical efficacy is hindered by poor solubility and bioavailability. Our study introduces the use of H-Ferritin nanocages (HFn) as a nanoformulation vehicle for Cur, aiming to enhance its therapeutic potential for AD. In this work, we characterized a nanoformulation of Cur in HFn (HFn-CUR) by evaluating its safety, stability, and its transport across the blood-brain barrier (BBB) in vitro. Moreover, we evaluated the efficacy of HFn-CUR by transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) from both AD patients and healthy controls (HC), and by using the well-established 5xFAD mouse model of AD., Results: Our data show that HFn-CUR exhibits improved water dispersibility, is non-toxic, and can traverse the BBB. Regarding its activity on PBMCs from AD patients, HFn-CUR enhances cellular responses to inflammation and reduces RAGE-mediated stress. Studies on an AD mouse model demonstrate that HFn-CUR exhibits mild beneficial effects on cognitive performance. Moreover, it effectively reduces microgliosis and astrogliosis and in vivo in mouse, suggesting potential neuroprotective benefits., Conclusions: Our data suggest that HFn-CUR is safe and effective in reducing inflammation in both in vitro and in vivo models of AD, supporting the need for further experiments to define its optimal use., Competing Interests: Declarations Ethics approval and consent to participate All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the Helsinki declaration and its later amendments or comparable ethical standards. The study design was examined by the IRBs of the enrolling institutions. The study protocol to obtain blood from patients was approved by the Ethical Committee of the IRCCS Mondino Foundation (Pavia, Italy) (Code: 20170001758). Informed consent was obtained from all subjects involved in the study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

CNS Drug discovery has been challenging due to the lack of clarity on CNS diseases' basic biological and pathological mechanisms. Despite the difficulty, some CNS drugs have been developed based on phenotypic effects. Herein, we propose a phenotype-structure relationship model, which predicts an anti-neuroinflammatory potency based on 3D molecular structures of the phenotype-active or inactive compounds without specifying targets. For this chemo-centric study, a predictive model of the nitric oxide (NO) inhibitory potency in hyper-activated microglia is built from the 548 agents, which were collected from 95 research articles (28 substructures consisting of natural products and synthetic scaffolds) and doubly externally validated by the agents of 9 research articles as third set. 3D Structures (multi-conformer ensemble) of every agent were encoded into the E3FP molecular fingerprint of the Keiser group as a 3D molecular representation. The location information of the molecular fingerprints could be learned and validated to classify the inhibitory potency of compounds (IC 50 cut-off between the active and inactive: 37.1 µM): (1) multi-layer perceptron (MLP) (AUC- CV : 0.997, AUC- Test : 0.992), (2) recurrent neural network (RNN) (AUC- CV : 0.999, AUC- Test : 0.995), and (3) convolutional neural network (CNN) (AUC- CV : 0.998, AUC- Test : 0.994). The high performance of these models was compared with that of four classical machine classification models (Logistic, Ridge, Lasso, and Naïve Bayes). We named the binary classification models NO-Classifier. Independent test set validation and decision region analysis of the independent test set doubly demonstrated NO-Classifier effectively discerned the anti-inflammatory potency of testing compounds in inflammatory cell phenotype with the webserver in https://no-classifier.onrender.com., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Periodontitis is a chronic inflammatory oral disease that causes defects in periodontal tissue. Conventional therapies are limited, and often lead to high recurrence rates. The emerging concept of medicinal food homology has shed light on the potential of ginger as a therapeutic adjuvant for periodontitis, given its antioxidant and anti-inflammatory properties. However, fresh ginger exhibits poor stability and bioavailability. Ginger exosome-like nanoparticles (GELNs), a derivative of ginger, have not been reported to exert therapeutic effects in periodontitis. This study aimed to explore the therapeutic effects of GELNs on tissue damage caused by periodontitis and their underlying mechanisms of action., Methods: The GELNs composition was analyzed using a widely targeted metabolome. Stability was assessed using nanoparticle tracking analysis (NTA) and zeta potential measurements, flavor was evaluated using an electronic nose, and membrane penetration was studied using confocal microscopy. A periodontitis model was established in SD rats, periodontal clinical indicators were monitored, and histological changes were assessed using H&E and TRAP staining. Co-culture experiments investigate the antioxidant and reparative abilities of GELNs on periodontal ligament fibroblasts (PDLFs) in inflammatory environment. NF-κB protein expression was examined by immunofluorescence and immunohistochemistry., Results: The findings revealed that GELNs demonstrated good stability in different environments and mitigated the pungent taste of the raw ginger. In vivo experiments showed that GELNs improved periodontal clinical parameters and pathology compared with ginger juice. In vitro data suggested that GELNs enhanced the proliferation and migration of PDLFs while reducing the reactive oxygen species (ROS) levels by inhibiting the NF-κB signaling pathway in an inflammatory setting., Conclusion: This study is the first to demonstrate that GELNs have a potential therapeutic effect on periodontitis. GELNs can alleviate oxidative stress (OS) and inflammatory reactions by inhibiting the NF-κB signaling pathway. These findings provide a promising method for the treatment of periodontitis by regulating an unbalanced OS state., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Xie et al.)

Inflammation is the physiological response of the immune system to injury or infection, typically manifested by local tissue congestion, swelling, heat, and pain. Prolonged or excessive inflammation can lead to tissue damage and the development of many diseases. The anti-inflammatory effects of natural ingredients have been extensively researched and confirmed. This study investigated the effects of Chlorogenic acid (CGA) isomers -- 3-Caffeolyquninic acid (3-CQA), 4-Caffeolyquninic acid (4-CQA), and 5-Caffeolyquninic acid (5-CQA) -- on the inflammatory response and oxidative stress reaction induced by LPS in RAW264.7 cells. Overall, 3-CQA exhibited the most significant reduction in levels of TNF-α, IL-6, NO, and ROS. 4-CQA showed superior inhibition of TNF-α compared to 5-CQA (p < 0.05), while no significant difference in other parameters. We further used DARTS and CETSA to demonstrate that CGA isomers have stable affinity with AKR1B1. As a positive control, the AKR1B1 antagonist epalrestat exhibited similar effects to the CGA isomers. 3-CQA having the smallest half-inhibitory concentration (IC50) for AKR1B1, while 4-CQA and 5-CQA have similar values. AutoDock simulations of the docking conformations revealed minimal differences in the average binding energies of the CGA isomers. The main differences were that VAL47 formed a hydrogen bond with 3-CQA, whereas GLN49 formed hydrogen bonds with 4-CQA and 5-CQA. Additionally, the number of hydrophobic bonds involving PHE122 and LEU300 varies. Our conclusion is that differences in non-covalent interactions result in the varying inhibitory abilities of CGA isomers on AKR1B1, which further affect the anti-inflammatory and antioxidant effects of CGA isomers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Electrospun fibers have been gaining popularity in ocular drug delivery and cellular therapies. However, most of electrospun fibers are planar-shape membrane with large dimension relative to intraocular space, making difficult to use as therapeutic implants. Herein, fibrous microtubes with a hollow center were fabricated by electrospinning using linear diblock mPEG 2000 -PLGA. Uniform microfibers with 0.809 μm diameter was tailored using Box-Behnken Design model for electrospinning process optimization. The microtubes were 1 mm long with a 0.386 mm diameter. Their suitability for intraocular administration was demonstrated by both injection via a 22-gauge needle and implant via integration of intraocular lens into the vitreous or anterior chamber of eyes, respectively. Electrospun mPEG 2000 -PLGA had higher porosity, smaller specific surface area, and smaller water contact angle, than that of PLGA. Macroscopically, mPEG 2000 -PLGA microfibers can maintain overall geometry upon exposure to aqueous buffer for 12 h while having high water uptake and exhibited good elasticity. Hydrolysis with 90 % polymeric degradation in 10.5 weeks underlied sustained slow release of anti-inflammatory drug dexamethasone. PEGylation of PLGA imparted preferential cell adhesion with markedly higher growth of human retinal epithelial cells than lens epithelial ones. This study highlights the potential utility of implantable electrospun PLGA-based microtubes for multiple intraocular delivery routes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The effective treatment of inflammatory diseases, particularly their chronic forms, is a key task of modern medicine. Herein, we report the synthesis and evaluation of biocompatible polymer conjugates based on N-2-(hydroxypropyl)methacrylamide copolymers enabling the controlled release of acetylsalicylic acid (ASA)-based anti-inflammatory drugs under specific stimuli. All polymer nanotherapeutics were proposed as water-soluble drug delivery systems with a hydrodynamic size below 10 nm ensuring suitability for the parenteral application and preventing opsonization by the reticuloendothelial system. The nanotherapeutics bearing an ester-bound ASA exhibited long-term release of the ASA/salicylic acid mixture, while the nanotherapeutics carrying salicylic acid hydrazide (SAH) ensured the selective release of SAH in the acidic inflammatory environment thanks to the pH-sensitive hydrazone bond between the polymer carrier and SAH. The ASA- and SAH-containing nanotherapeutics inhibited both cyclooxygenase isoforms and/or the production of pro-inflammatory mediators. Thanks to their favorable design, they can preferentially accumulate in the inflamed tissue, resulting in reduced side effects and lower dosage, and thus more effective and safer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Constant efforts have been made to move towards maintaining the positive anti-inflammatory functions of glucocorticoids (GCs) while minimizing side effects. The anti-inflammatory effect of GCs is mainly attributed to the inhibition of major inflammatory pathways such as NF-κB through GR transrepression, while its side effects are mainly mediated by transactivation. Here, we investigated the selective glucocorticoid receptor modulator (SGRM)-like properties of a plant-derived compound. In this study, glucocorticoid receptor (GR)-mediated alleviation of inflammation by SP-8 was investigated by a combination of in vitro, in silico, and in vivo approaches. Molecular docking and cellular thermal shift assay suggested that SP-8 bound stably to the active site of GR via hydrogen bonding and hydrophobic interactions. SP-8 activated GR, induced GR nuclear translocation, and inhibited NF-κB pathway activation. Furthermore, SP-8 did not up-regulate the gene and protein expression of PEPCK and TAT in HepG2 cells, and it did not induce fat deposition like GC and has little effect on bone metabolism. Interestingly, SP-8 upregulated GR protein expression and did not cause GR phosphorylation at Ser211 in RAW264.7 cells. This work proved that SP-8 dissociated characteristics of transrepression and transactivation can be separated. In addition, the in vitro and in vivo anti-inflammatory effects of SP-8 were confirmed in LPS-induced RAW 264.7 cells and in a mouse model of DSS-induced ulcerative colitis, respectively. In conclusion, SP-8 might serve as a potential SGRM and might hold great potential for therapeutic use in inflammatory diseases., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We the undersigned declare that this manuscript is original, has not been published before and is not currently being considered for publication elsewhere. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We understand that the Corresponding Author is the sole contact for the Editorial process. She is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs., (Copyright © 2024. Published by Elsevier B.V.)

Gelidium sesquipedale is valued in the Spanish agar industry, but its production generates substantial waste, often discarded despite its nutritional and bioactive content. Subcritical water extraction (SWE) at 175 °C and 50 bar for 130 min was performed on this waste after agar extraction, comparing it to conventional ethanol extraction. The SWE extract exhibited superior nutritional profile, including proteins (170.6 ± 1.0 mg/g freeze-dried-extract ), essential amino acids (18.1%), carbohydrates (148.1 ± 0.3 mg/g freeze-dried-extract ), total phenolic content (57 ± 7 mg-EqGA/g freeze-dried-extract ), and also containing Maillard reaction compounds, such as 5-hydroxymethylfurfural, furfural, 2-furanmethanol, 1-(2-furanyl)-ethanone, and 5-methyl-2-furfural, influencing color, aroma and flavor. This extract showed better antioxidant and anti-inflammatory properties than the conventional extract, and higher xanthine oxidase, tyrosinase, and acetylcholinesterase inhibition activities. Toxicological assessment on human cells indicated the safety of the SWE extract. Therefore, SWE technology offers a promising method to valorize G. sesquipedale residue, yielding a bioactive and nutrient-rich extract suitable for food and nutraceutical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Eleven compounds including caffeic acid (CA), 4 kinds of caffeoylquinic acid (CQA) and 6 kinds of dicaffeoylquinic acid (DCQA), were selected to evaluate the anti-inflammatory effectiveness using mouse primary peritoneal macrophages in the absence or presence of lipopolysaccharide (LPS). The optimal non-cytotoxic doses of each individual compound were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Pro-inflammatory (TNF-α, IL-1β, IL-6) and anti-inflammatory (IL-10) cytokines secreted by treated macrophages were analyzed using the enzyme-linked immunosorbent assay. Cytokine secretion profiles of each individual test sample at optimal non-cytotoxic doses were further analyzed using Principal Component Analysis (PCA). The results showed that CA and all selected CQAs exhibited lower cytotoxicity (IC 50 : >50 μmol/l). Both CA and 5-CQA were found to have the most significant contributions for inhibiting pro-inflammatory cytokines, but increasing anti-inflammatory cytokine secretions, evidencing that CA at 10 μmol/l and 5-CQA at 25 μmol/l can be qualified as potent anti-inflammatory agents for treating inflammation-related diseases., Competing Interests: Declaration of competing interest The authors declare that there is no known competing interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Plant vernacular names can provide clues about the popular use of a species in different regions and are valuable sources of information about the culture or vocabulary of a population. Several medicinal plants in Brazil have received names of medicines and brand-name products., Aim of the Study: The present work aimed to evaluate the chemical composition and pharmacological activity in the central nervous system of three species known popularly by brand names of analgesic, anti-inflammatory, antispasmodic, and digestive drugs., Materials and Methods: Hydroethanolic extracts of Alternanthera dentata (AD), Ocimum carnosum (OC), and Plectranthus barbatus (PB) aerial parts were submitted to phytochemical analysis by HPLC-PAD-ESI-MS/MS and evaluated in animal models at doses of 500 and 1000 mg/kg. Mice were tested on hot plate, acetic acid-induced writing, formalin-induced licking, and intestinal transit tests. Aspirin and morphine were employed as standard drugs., Results: The three extracts did not change the mice's response on the hot plate. Hydroethanolic extracts of AD and PB reduced the number of writhes and licking time, while OC was only effective on the licking test at dose of 1000 mg/kg. In addition, AD and OC reduced intestinal transit, while PB increased gut motility., Conclusions: Pharmacological tests supported some popular uses, suggesting peripheral antinociceptive and anti-inflammatory effects, while the phytochemical analysis showed the presence of several flavonoids in the three hydroethanolic extracts and steroids in PB, with some barbatusterol derivatives described for the first time in the species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In addition to their pigment properties, the potential health benefits of anthocyanins have made them a subject of interest in recent years. This study aimed to obtain purified anthocyanin fractions from native Mexican black bean cultivars using Amberlite XAD-7 resin column and HPCCC and evaluate their anti-inflammatory properties using RAW 264.7 cells. The major anthocyanins in the purified anthocyanin fractions were delphinidin 3-glucoside (61.8%), petunidin 3-glucoside (25.2%), and malvidin 3-glucoside (12.2%). Purified anthocyanin fractions at 12.5 μg/mL effectively prevented LPS-induced ERK1/ERK2 phosphorylation and reduced the protein expression of COX-2 and mRNA expression of iNOS. Results showed that purified anthocyanin fractions have the potential to modulate the inflammatory response by inhibiting the production of pro-inflammatory mediators through the ERK1/ERK2 and NF-κB pathways. This study suggests that anthocyanins from black beans could be used as a natural strategy to help modulate inflammation-associated diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Treating psoriasis presents a major clinical challenge because of the limitations associated with traditional topical glucocorticoid therapy. This study introduced a drug delivery system utilizing zinc-doped mesoporous silica nanoparticle (Zn-MSN) and microneedle (MN), designed to enhance drug utilization for prolonged anti-inflammatory and anti-itch effects. The MN system facilitated the transdermal delivery of betamethasone dipropionate (BD), allowing its slow release. The BD@Zn-MSN-MN system promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype, achieving superior anti-inflammatory effects compared to the clinically used BD cream. Additionally, this study demonstrated that BD@Zn-MSN-MN could further alleviate itching in psoriasis-afflicted mice by decreasing the excitability of the transient receptor potential vanilloid V1 (TRPV1) ion channel positive neurons and reducing the release of calcitonin gene-related peptide (CGRP) in the dorsal root ganglion (DRG). These findings offer new insights and effective therapeutic options for the future design of transdermal drug delivery for psoriasis., Competing Interests: Declarations Ethics approval and consent to participate The animal experiments were approved by the Ethics Committee for Experimental Use of Animals of the Shanghai Jiao Tong University School of Medicine (approval code: #SYXK-2013-0050). Consent for publication All authors agree for publication. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

We developed two short helical antimicrobial peptides, HVF18-a3 and its d-enantiomer, HVF18-a3-d, derived from the thrombin C-terminal peptide HVF18. These peptides exhibit potent antimicrobial activity against various bacteria by compromising both the outer and inner membranes, with low hemolytic activity. They are stable in the presence of physiological salts and human serum, exhibiting a low potential for developing drug resistance and excellent antibiofilm activity against Gram-negative bacteria. HVF18-a3-d also neutralized lipopolysaccharide (LPS) through direct binding interactions and suppressed the production of inflammatory cytokines through the inflammatory signaling pathway mediated by Toll-like receptor 4 in RAW264.7 cells stimulated with LPS. Both pre- and post-treatment with HVF18-a3-d significantly protected mice against fatal septic shock induced by carbapenem resistant Acinetobacter baumannii . These findings suggest HVF18-a3 and HVF18-a3-d are promising candidates for developing antibiotics against Gram-negative sepsis.

Background: Budesonide (BUD) is a BCS class II medication with poor water solubility and limited oral bioavailability. In this study, innovative solid self-microemulsifying drug delivery systems (BUD-SMEDDS) were developed for effective local management of distal ulcerative colitis (UC)., Methods: Based on solubility and emulsification tests, the components of the self-microemulsifying drug delivery system (SMEDDS) were Capryol™ 90, Tween 80, and Transcutol HP. The impacts of BUD-SMEDDS ingredients (as inputs) on the average globule size (AGS), polydispersity index (PDI), and self-emulsification time (SET) as responses were investigated using the Box-Behnken design methodology. Solid rectal systems were then fabricated using the optimized values of SMEDDS components in Lutrol ® bases. The developed systems were evaluated for in vitro characteristics and in vivo efficacy using a rat colitis model., Results: For all responses, the greatest impact was attributed to the oil content of SMEDDS. An optimized BUD-SMEDDS with AGS of 33 ± 2.9 nm, PDI of 0.29 ± 0.03 and SET of 25 ± 2.5 s) was selected for rectal formulations. The developed formulations demonstrated acceptable physical characteristics and mucoadhesive abilities. Differential scanning calorimetric (DSC) analysis revealed the absence of BUD crystallinity in the SMEDDS formulations. The drug release patterns could be regulated by selecting the grade and composition of the incorporated Lutrols. Clinical and histopathological assessments revealed considerable improvements in animals treated with BUD-SMEDDS formulations., Conclusion: Overall findings confirmed the superior capability of solid SMEDDS as BUD carriers to manage distal colitis in tested animals., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Ali et al.)

Inflammatory bowel disease (IBD) treatment often involves systemic administration of anti-inflammatory drugs or biologics such as anti-TNF-α antibodies. However, current drug therapies suffer from limited efficacy due to unresponsiveness and adverse side effects. To address these challenges, we developed inflammation-targeting nanoparticles (ITNPs) using biopolymers derived from the gum kondagogu (Cochlospermum gossypium) plant. These ITNPs enable selective drug delivery to inflamed regions, offering improved therapeutic outcomes. We designed ITNPs that specifically bind to inflamed regions in both human and mouse intestines, facilitating more effective, uniform, and prolonged drug delivery within the inflamed tissues. Furthermore, we demonstrated that oral administration of ITNPs loaded with urolithin A (UroA), a microbial metabolite or its synthetic analogue UAS03 significantly attenuated chemical- and immune checkpoint inhibitor- induced colitis in pre-clinical models. In conclusion, ITNPs show great promise for delivering UroA or its analogues while enhancing therapeutic efficacy at lower doses and reduced frequency compared to free drug administration. This targeted approach offers a potential solution to enhance IBD treatment while minimizing systemic side effects., Competing Interests: Declarations Competing interests VRJ and PKV are co-founders of Artus Therapeutics. Others declare no competing interest. Classification Biological Sciences, Immunology and Inflammation, Applied Biological Sciences., (© 2024. The Author(s).)

Wound healing is a complex biological process that can trigger inflammation and oxidative stress and impair myofibrillogenesis and angiogenesis. Several advanced wound-dressing nanocomposite materials have been designed to address these issues. Here, we designed a new multifunctional styrene-ethylene-butylene-styrene/silver nanowire (SEBS/AgNWs)-based nanocomposite film with antimicrobial, antioxidant, and anti-inflammatory properties to promote wound healing. The porous morphological structure of SEBS/AgNWs enhances their antimicrobial, antioxidant, and anti-inflammatory properties. SEBS/AgNWs significantly inhibited the growth of Staphylococcus aureus , methicillin-resistant Staphylococcus aureus , and Escherichia coli strains, effectively wiping out ABTS•+, DPPH•, hydrogen peroxide (H 2 O 2 ), and hydroxyl (•OH) radicals, showing their effective ROS-scavenging properties. It further showed significant antioxidant properties by increasing the levels of enzyme-like catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH), while decreasing malonaldehyde (MDA) levels. Additionally, SEBS/AgNWs reduced the expression of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), while increasing levels of transforming growth factor- β (TGF-β), vascular endothelial growth factor-A (VEGF), and CD31 in wound healing. This suggests that applying a multifunctional nanoplatform based on SEBS/AgNWs could enhance wound healing and improve patient outcomes in wound care management.

Covering: 2019 to 2023Isoquinoline alkaloids, an important class of N -based heterocyclic compounds, have attracted considerable attention from researchers worldwide. To follow up on our prior review (covering 2014-2018) and present the progress of this class of compounds, this review summarizes and provides updated literature on novel isoquinoline alkaloids isolated during the period of 2019-2023, together with their biological activity and underlying mechanisms of action. Moreover, with the rapid development of synthetic modification strategies, the synthesis strategies of isoquinoline alkaloids have been continuously optimized, and the total synthesis of these classes of natural products is reviewed critically herein. Over 250 molecules with a broad range of bioactivities, including antitumor, antibacterial, cardioprotective, anti-inflammatory, neuroprotective and other activities, are isolated and discussed. The total synthesis of more than nine classes of isoquinoline alkaloids is presented, and thirteen compounds constitute the first total synthesis. This survey provides new indications or possibilities for the discovery of new drugs from the original naturally occurring isoquinoline alkaloids.

Metal-free radical cascade synthesis of substituted pyrazole derivatives was initiated by PhI(OAc) 2 at 23 °C. This protocol features wide functional group tolerance, a simple purification process without column chromatography, and an oxygen migration. Compound 5 demonstrated significant anti-inflammatory activity, indicating potential for therapy.

Moisture loss, infection, and severe inflammatory reactions are the primary factors affecting burn wound healing and leading to scar formation. Herein, we developed a quercetin-loaded polysaccharide-based injectable hydrogel (named PECE). The PECE consists of oxidized sodium alginate (OAlg) coupled with chitosan (CS) via Schiff bases and electrostatic interactions, while Que is incorporated via hydrogen bonding. Benefiting from the hydroxyl and carboxyl groups, PECE features distinguished moisturizing ability. Additionally, the sustained release of Que imparts remarkable antibacterial activity against Escherichia coli and Staphylococcus aureus . Likewise, PECE demonstrates favorable in vitro anti-inflammatory capacity as released Que significantly downregulates pro-inflammatory factors (IL-6 and TNF-α) secreted by RAW 264.7 macrophages. More importantly, in a rat model of deep second-degree burn wounds, PECE effectively inhibits wound infection, reduces inflammation, and promotes angiogenesis and collagen deposition, ultimately minimizing scar formation. Overall, this work presents a promising strategy for scarless healing of burn wounds.

Infection with drug-resistant bacteria and the formation of biofilms are the main factors contributing to wound healing insufficiency. Antibacterial agents with enzyme-like properties have exhibited considerable potential for efficient eradication of drug-resistant microorganisms due to their superior sensitivities and minimal side effects. In this work, we prepared a kind of Fe-centered single-atom nanozyme (Fe-SAzyme) with high biocompatibility and stability via a facile one-pot hydrothermal method, which was suitable for the treatment of wounds infected with drug-resistant bacteria. The Fe-SAzyme exhibited remarkable peroxidase-like catalytic activities, catalyzing the conversion of hydrogen peroxide (H 2 O 2 ) to highly toxic hydroxyl radicals ( • OH), which could not only damage bacterial cells but also inhibit, disrupt, and eradicate the formation of bacterial biofilms. Thus, Fe-SAzyme demonstrated a broad-spectrum antibacterial performance capable of effectively eliminating multidrug-resistant bacteria. The coexistence of ferrous (Fe 2+ ) and ferric (Fe 3+ ) ions in Fe-SAzyme conferred the nanozyme with anti-inflammatory activity, effectively suppressing excessive inflammation. Meanwhile, Fe-SAzyme could significantly downregulate inflammatory cytokines tumor necrosis factor-α and interleukin-1β and upregulate growth factors VEGF and epidermal growth factor, which can prevent bacterial infection, mitigate inflammation, promote fibroblast proliferation, and improve wound closure. Thus, Fe-SAzyme had shown favorable therapeutic efficiency in promoting bacteria-infected wound healing. This study provides Fe-SAzyme as a promising candidate for the development of new strategies to treat multidrug-resistant bacterial infections.

Background: Green synthesized nanoparticles have recently gained significant medicinal applications and oftentimes outperform their green sources. Selenium is of fundamental importance to human health, stemming from its distinctive physicochemical properties, such as antioxidant activity, inhibition of Lipid peroxidation, stabilization of membrane proteins, maintenance of membrane fluidity and modulation of cell signaling. Though reports have shown some therapeutic potential of Ackee plant parts such as antioxidant, anti-inflammatory, antimicrobial, neuroprotective, very few scientific proofs still exist in support of these effects., Methods: This study synthesized selenium nanoparticles (Se-NPs) from crude methanolic extracts of Ackee leaves (AKL) and Ackee arils (AKA), examined the photo-physical characteristics of the Se-NPs and determined the in-vitro antioxidant, antidiabetic, and anti-inflammatory potentials of AKL, AKA, and their Se-NPs using established protocols., Results: In both leaves and arils Se-NPs: UV spectroscopy revealed a qualitative absorbance at 310 nm; FTIR indicated multiple vibrations around 4000 cm -1 - 400 cm -1 ; SEM images of 5 µm principally showed consistent size distribution of amorphous and granular shape at a magnification of 10,000X; while EDS spectra strongly confirm the presence of atomic Se compound at 30 kV. Various antioxidant activities assays carried out showed a range of approximately 4 to 60 times higher activities of the AKL, AKA, and Se-NPs than Ascorbic acid-the standard drug used. Furthermore, appreciable activities of more than 50% were obtained for alpha-amylase and alpha-glucosidase inhibitory activities, along with highly significant activities of haemoglobin glycosylation, glucose uptake, membrane stabilization, anti-arthritic, anti-haemolysis activities, when AKL, AKA, and Se-NPs were compared with standard drugs., Conclusion: Encouraging the development and utilization of AKL, AKA, and Se-NPs will provide tremendous therapeutic efficacy and bioavailability approaches towards the management of diabetes, inflammation, and other oxidative stress-related diseases., (© 2024. The Author(s).)

Eleven new macrocyclic casbane-type diterpenes, namely sinueracasbanones E-O (1-11), have been isolated from the South China Sea soft coral Sinularia erecta using combined column chromatography. The structures of new compounds were elucidated by extensive spectroscopic data analysis, the modified Mosher's method, X-ray diffraction analysis and quantum mechanical calculation methods. In bioassay, compounds 2, 5, 10 and 11 displayed interesting anti-inflammatory activities by the inhibition of lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α protein release with half maximal inhibitory concentration (IC 50 ) values of 15.6, 7.1, 13.7 and 6.6 µM, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Atorvastatin (ATV), a medication used to reduce cholesterol levels, possesses properties that can counteract the damaging effects of free radicals and reduce inflammation. However, the administration of ATV orally is associated with low systemic bioavailability due to its limited capacity to dissolve in water and significant first-pass effect. This study aimed to assess the appropriateness of employing nano-vesicles for transdermal administration of ATV in order to enhance its anti-inflammatory effects., Methods: ATV-loaded transethosomes (ATV-TEs) were optimized using the 3 3 Box-Behnken design. The ATV-TEs that were created were evaluated for their vesicle size, encapsulation efficiency (% EE), and percent release of drug. The optimum formulation was integrated into a hydroxypropyl methylcellulose (HPMC) emulsion-based gel (ATV-TEs emulgel) using jojoba oil. ATV-TEs emulgel was examined for its physical characteristics, ex vivo permeability, histological, and anti-inflammatory effect in a rat model of inflamed paw edema., Results: The optimized transethosomes exhibited a vesicle size of 158.00 nm and an encapsulation efficiency of 80.14 ± 1.42%. Furthermore, the use of transethosomal vesicles effectively prolonged the release of ATV for a duration of 24 hours, in contrast to the pure drug suspension. In addition, the transethosomal emulgel loaded with ATV exhibited a 3.8-fold increase in the transdermal flow of ATV, in comparison to the pure drug suspension. ATV-TEs emulgel demonstrated a strong anti-inflammatory impact in the carrageenan-induced paw edema model., Discussion: This was evident from the significant reduction in paw edema, which was equivalent to the effect of the standard anti-inflammatory medicine, Diclofenac sodium., Conclusion: In summary, transethosomes, as a whole, might potentially serve as an effective method for delivering drugs via the skin. This could improve the ability of ATV to reduce inflammation by increasing its absorption through the skin., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Abdallah et al.)

Emergency wounds are often accompanied by bacterial infection, oxidative stress, and excessive inflammation due to the inability to quickly close and stop bleeding, resulting in chronic wounds that are difficult to heal. Clinically, surgical suturing is the fastest method for wound closure, but it is only suitable for wounds with small bleeding volumes and causes unsightly scar formation. Consequently, there is a critical need for hemostatic dressings versatile enough to address a spectrum of diverse and intricate wounds, especially in emergency scenarios. In this study, we constructed a unique versatile natural gelatin-based hydrogel with hemostasis, antibacterial, and anti-inflammation properties. The hydrogel was composed of 4-(4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy) butyrylethylenediamine-modified methacrylated gelatin (GelMA-NB) and epigallocatechin gallate-grafted polylysine (EPL-EGCG), which imparts adhesion, antibacterial and antioxidant properties to the hydrogel. Simultaneously, the hydrogel was loaded with GelMA microspheres encapsulating natural resveratrol (RES@GM). This combination not only exhibited outstanding hemostatic capabilities but also preserved the anti-inflammatory potential of RES. In different animal models, the hydrogel exhibited outstanding hemostatic and wound healing effects, down-regulated the expression of IL-1 β to promote inflammatory regulation and potential for angiogenesis and anti-scar. In conclusion, unique versatile natural gelatin-based hydrogel suitable for various complex wounds provides a promising strategy for emergency wound dressing applications., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

This study aims to explore the efficacy and safety of macrophage membrane-coated nanoparticles for the delivery of natamycin (NAT) in the therapy of fungal keratitis (FK). Macrophage membranes were isolated and identified by immunofluorescence staining (IFS). NAT was encapsulated into poly(lactic- co -glycolic acid) (PLGA). Fungal stimulated macrophage membranes (M1) or unstimulated membranes (M) were separately mixed and sonicated with PLGA nanoparticles. The biocompatible nanoparticles (PLGA-NAT, PLGA-NAT@M, and PLGA-NAT@M1) were characterized with zeta-sizer analysis, transmission electron microscopy (TEM), and Western blot. Drug encapsulation and loading efficiency and the release of NAT in the nanoparticles were detected by ultraviolet spectrophotometry. The cytotoxicity, ocular surface toxicity and irritability, and systemic safety of nanoparticles with different concentrations were assessed. In vitro, we examined the antifungal properties of the nanoparticles. The eye surface retention time, drug release, and curative effects on FK were evaluated in vitro and in vivo. IFS results showed the separation of the macrophage membrane and nucleus. The prepared nanoparticles had a typical "core-shell" structure and uniform nanometer size, and the membrane proteins were retained on the membrane allowing to exert functional effects of macrophage. The loading efficiencies of PLGA-NAT@M and PLGA-NAT@M1 were 7.6 and 6.7%, respectively. The encapsulation efficiencies of PLGA-NAT@M and PLGA-NAT@M1 were 51.2 and 41.5%, respectively. PLGA-NAT@M and PLGA-NAT@M1 could gradually release NAT and reduce the clearance of the ocular surface. Macrophage membranes enhanced the antifungal activity of PLGA-NAT. Furthermore, the membrane coated with macrophage increased the biocompatibility and decreased the corneal toxicity of nanoparticles. In vivo, PLGA-NAT@M1 significantly alleviated the severity of FK. In vitro, PLGA@M and PLGA@M1 reduced the protein levels of inflammatory cytokines after fungal stimulation. The prepared PLGA-NAT@M1 has good physical properties and biosafety. It could evade ocular surface clearance, release NAT gradually, and achieve high antifungal and anti-inflammatory efficiencies to FK. Macrophage membrane-coated nanoparticles clinically have high application potential to the treatment of FK.

Rheumatoid arthritis (RA) is a chronic disease characterized by immune cell infiltration and cartilage damage. The local lesion of RA shows severe oxidative stress and proinflammatory cytokine secretion. For drug therapy, the efficacy of agents, such as methotrexate (MTX), may be greatly limited, resulting from the low bioavailability, immune clearance, and toxic side effects. A nanocarrier (TA-PBA NPs) was developed with anti-inflammatory and antioxidant activities, combined with MTX to prepare nanomedicine (MTX NPs) for synergistic treatment of RA. Moreover, inspired by the biological functions homing to inflammation lesion of macrophages, the biomimetic nanomedicine camouflaged with macrophage membrane (MM@MTX NPs) was constructed. TA-PBA NPs could timely promote MTX release in response to the overaccumulated ROS to exhibit high anti-inflammatory and antioxidant activities for alleviating RA progression. The experimental results confirmed that MM@MTX NPs could significantly reduce the secretion of proinflammatory cytokines (TNF-α) while significantly increasing the typical anti-inflammatory cytokines (IL-10), promote the phenotype transformation of macrophages from M1 to M2, and up-regulate the Nrf2-keap1 pathway-related proteins (HO-1 and NRF2) to positively regulate the local inflammation for effectively inhibiting RA development. Thus, MM@MTX NPs represent a possible candidate as a safe and efficient nanotherapy platform for RA management.

Targeted delivery of anti-inflammatory drugs to macrophages has attracted great attention for selectively alleviating the symptoms of ulcerative colitis (UC), while minimizing adverse effects. Herein, we aimed to compare the in vivo pharmacokinetics and therapeutic outcomes of macrophage-targeted nanoparticles (NPs) via oral administration and intravenous injection. Polymeric NPs were employed to load an anti-inflammatory drug (curcumin, CUR), followed by surface functionalization with hyaluronic acid (HA). The resulting HA-CUR-NPs had an average diameter of 281 nm and a negatively charged surface. These NPs showed excellent biocompatibility and a significantly higher cell internalization efficiency in RAW 264.7 macrophages compared with their counterparts (carboxymethyl cellulose-functionalized CUR-encapsulated NPs, CUL-CUR-NPs). Moreover, HA-CUR-NPs exhibited a dramatically stronger capacity to inhibit the mRNA expression levels of the typical pro-inflammatory cytokines from lipopolysaccharide-stimulated macrophages compared with CUL-CUR-NPs. In vivo experiments revealed that HA-CUR-NPs after i.v. injection could improve the pharmacokinetics of CUR, and that it showed much better UC therapeutic outcomes compared with the oral administration way. Collectively, in comparison with HA-CUR-NPs (oral), HA-CUR-NPs (i.v.) possess a higher CUR delivery efficiency to the colitis mucosa, which can be developed as an efficient platform for UC treatment.

Background: Human neutrophil elastase (HNE) is an important contributor to lung diseases such as acute lung injury (ALI) or acute respiratory distress syndrome. Therefore, this study aimed to identify natural HNE inhibitors with anti-inflammatory activity through machine learning algorithms, in vitro assays, molecular dynamic simulation, and an in vivo ALI assay., Methods: Based on the optimized Discovery Studio two-dimensional molecular descriptors, combined with different molecular fingerprints, six machine learning models were established using the Naïve Bayesian (NB) method to identify HNE inhibitors. Subsequently, the optimal model was utilized to screen 6925 drug-like compounds obtained from the Traditional Chinese Medicine Systems Pharmacy Database and Analysis Platform (TCMSP), followed by ADMET analysis. Finally, 10 compounds with reported anti-inflammatory activity were selected to determine their inhibitory activities against HNE in vitro, and the compounds with the best activity were selected for a 100 ns molecular dynamics simulation and its anti-inflammatory effect was evaluated using Poly (I:C)-induced ALI model., Results: The evaluation of the in vitro HNE inhibition efficiency of the 10 selected compounds showed that the flavonoid tricetin had the strongest inhibitory effect on HNE. The molecular dynamics simulation indicated that the binding of tricetin to HNE was relatively stable throughout the simulation. Importantly, in vivo experiments indicated that tricetin treatment substantially improved the Poly (I:C)-induced ALI., Conclusion: The proposed NB model was proved valuable for exploring novel HNE inhibitors, and natural tricetin was screened out as a novel HNE inhibitor, which was confirmed by in vitro and in vivo assays for its inhibitory activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

N-heterocyclic carbenes (NHCs) represent suitable ligands for rapid and efficient drug design, because they offer the advantage of being easily chemically modified and can bind several substituents, including transition metals as, for instance, gold derivatives. Gold-NHC complexes possess various biological activities and were demonstrated good candidates as anticancer drugs. Besides, carbazole derivatives are characterized by various pharmacological properties, such as anticancer, antibacterial, anti-inflammatory, and anti-psychotropic. Amongst the latter, N-thioalkyl carbazoles were proved to inhibit cancer cells damaging the nuclear DNA, through the inhibition of human topoisomerases. Herein, we report the design, synthesis and biological evaluation of nine new hybrid molecules in which NHC-Au(I) complexes and N-alkylthiolated carbazoles are linked together, in order to obtain novel biological multitarget agents. We demonstrated that the lead hybrid complexes possess anticancer, anti-inflammatory and antioxidant properties, with a high potential as useful tools for treating distinct aspects of several diseases, amongst them cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

In recent years, two-dimensional transition metal carbides, nitrides, and carbonitrides, termed as MXenes, have been widely applied in energy storage, photocatalysis and biomedicine owing to their unique physicochemical properties of large specific surface area, high electrical conductivity, excellent optical performance, good stability, etc. Moreover, due to their strong light absorption capacity in the first and second near-infrared bio-window, and their ability of being simply functionalized with multiple organic/inorganic materials, MXene biomaterials have shown great potential in the field of catalytic therapy. This review will summarize the common catalytic mechanism of MXene biomaterials and their latest applications in catalytic medicine such as tumor therapy, antibacterial and anti-inflammatory, and present the current challenges and opportunities in clinical translation for future development to promote the advancement of MXene biomaterials in the field of catalytic medicine., (© 2024 Wiley-VCH GmbH.)

Burn wounds pose intricate clinical challenges due to their severity and high risk of complications, demanding advanced therapeutic strategies beyond conventional treatments. This review discusses the application of nanoparticle-based therapies for optimizing burn wound healing. We explore the critical phases of burn wound healing, including inflammation, proliferation, and remodeling, while summarizing key nanoparticle-based strategies that influence these processes to optimize healing. Various nanoparticles, such as metal-based, polymer-based, and extracellular vesicles, are evaluated for their distinctive properties and mechanisms of action, including antimicrobial, anti-inflammatory, and regenerative effects. Future directions are highlighted, focusing on personalized therapies and the integration of sophisticated drug delivery systems, emphasizing the transformative potential of nanoparticles in enhancing burn wound treatment., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Shi et al.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally, with only one Food and Drug Administration (FDA)-approved drug for its treatment. Given MASLD's complex pathophysiology, therapies that simultaneously target multiple pathways are highly desirable. One promising approach is dual-modulation of the farnesoid X receptor (FXR), which regulates lipid and bile acid metabolism. However, FXR agonists alone are insufficient due to their limited anti-inflammatory effects. This study aimed to dto identify natural products capable of both FXR activation and inflammation inhibition to provide a comprehensive therapeutic approach for MASLD. Potential FXR ligands from the Natural Product Library were predicted via virtual screening using the Protein Preparation Wizard module in Schrodinger (2018) for molecular docking. Direct binding and regulation of candidate compounds on FXR were analyzed using surface plasmon resonance (SPR) binding assay, reporter gene analysis, and reverse transcription-polymerase chain reaction (RT-PCR). The anti-inflammatory properties of these compounds were evaluated in AML12 cells treated with tumor necrosis factor-alpha (TNF-α). Dual-function compounds with FXR agonism and inflammation inhibition were further identified in cells transfected with Fxr siRNA and treated with TNF-α. The effects of these dual-function compounds on lipid accumulation and inflammation were evaluated in cells treated with palmitic acid. Results revealed that 17 natural products were predicted via computational molecular docking as potential FXR agonists, with 15 exhibiting a strong affinity for FXR recombinant protein. Nine isoflavone compounds significantly enhanced FXR reporter luciferase activity and the mRNA expressions of Shp and Ostb. Structure-activity relationship analysis indicated that introducing isopropyl or methoxy groups at the C7 position or a methoxy group at the C6 position could enhance the agonistic efficacy of isoflavones. Three compounds (2, 6, and 8) were identified as dual-function natural products functioning as FXR agonists and inflammatory inhibitors, while one compound (12) acted as an FXR agonist to inhibit inflammation. These natural products protected hepatocytes against palmitic acid-induced lipid accumulation and inflammation. In conclusion, compounds 2, 6, and 8 (genistein, biochanin A, and 7-methoxyisoflavone, respectively) were identified as dual-function bioactive products that transactivate FXR and inhibit inflammation, serving as potential candidates or lead compounds for MASLD therapy., (Copyright © 2024 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Background: Fungal keratitis is a serious blinding eye disease. Traditional drugs used to treat fungal keratitis commonly have the disadvantages of low bioavailability, poor dispersion, and limited permeability., Purpose: To develop a new method for the treatment of fungal keratitis with improved bioavailability, dispersion, and permeability., Methods: Zeolitic Imidazolate Framework-8 (ZIF-8) was formed by zinc ions and 2-methylimidazole linked by coordination bonds and characterized by Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Zeta potential. The safety of ZIF-8 on HCECs and RAW 264.7 cells was detected by Cell Counting Kit-8 (CCK-8). Safety evaluation of ZIF-8 on mice corneal epithelium was conducted using the Draize corneal toxicity test. The effects of ZIF-8 on fungal growth, biofilm formation, and hyphae structure were detected by Minimal inhibit concentration (MIC), crystal violet staining, Propidium Iodide (PI) testing, and calcofluor white staining. The anti-inflammatory effects of ZIF-8 on RAW 246.7 cells were evaluated by Quantitative Real-Time PCR Experiments (qPCR) and Enzyme-linked immunosorbent assay (ELISA). Clinical score, Colony-Forming Units (CFU), Hematoxylin-eosin (HE) staining, and immunofluorescence were conducted to verify the therapeutic effect of ZIF-8 on C57BL/6 female mice with fungal keratitis., Results: In vitro, ZIF-8 showed outstanding antifungal effects, including inhibiting the growth of Aspergillus fumigatus over 90% at 64 μg/mL, restraining the formation of biofilm, and destroying cell membranes. In vivo, treatment with ZIF-8 reduced corneal fungal load and mitigated neutrophil infiltration in fungal keratitis, which effectively reduced the severity of keratitis in mice and alleviated the infiltration of inflammatory factors in the mouse cornea. In addition, ZIF-8 reduces the inflammatory response by downregulating the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β after Aspergillus fumigatus infection in vivo and in vitro., Conclusion: ZIF-8 has a significant anti-inflammatory and antifungal effect, which provides a new solution for the treatment of fungal keratitis., Competing Interests: The authors declare no conflict of interest., (© 2024 Fu et al.)

Curcumin (Cur) exerts many benefits on the host, but its application is limited by its poor bioavailability. In this study, composite polysaccharide microparticles loading Cur (Cur-CPM) was prepared by food-grade materials and gel technology. Its properties were analyzed via the in vitro and in vivo models, and then its benefit on gut health was assessed in DSS-treated mice. Compared to free Cur, CPM extended the residence time and absorption efficiency of Cur in the intestine, effectively ameliorating the symptoms of colitis. Cur-CPM alleviated colonic inflammation by inhibiting the activation of the MAPK and NF-κB pathways and suppressing NLRP3 inflammasome activity, affecting the expression of inflammation-related cytokines and mediators. In addition, Cur-CPM regulated the levels of antioxidants and oxidants in the colon tissues via Nrf2 activation, alleviating oxidative stress. Cur-CPM protected gut barrier function by maintaining the integrity of colonic mucosal layer and tight junction. The underlying mechanism can be attributed not only to the anti-inflammatory and antioxidant activities of Cur but also to modulation of Cur and CPM on the gut microbiota and metabolites. It suggests that Cur-CPM holds the potential to be developed as a functional component to enhance gut health., Competing Interests: Declaration of competing interest All authors have no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Fermenting edible filamentous fungi with food industry by-products, such as young apples, shows promise for producing mycoproteins and functional peptides. This study aimed to evaluate the production of mycoprotein by fermenting different edible-grade filamentous fungi using young apples as a substrate. Schizophyllum commune DS1 (DS1) demonstrated significant potential for generating mycoprotein, yielding 33.56 ± 0.82 %. From the hydrolysis of DS1 mycoprotein, three polypeptides were identified with the capacity of inhibiting nitric oxide synthase (iNOS): DNIQGITKPAIR (DR12), SDNAFGGR (SR8), and ASDPSGF (AF7). Computational analysis, including bioinformatics and molecular docking, indicated their high affinity for inhibiting iNOS, with binding energies of -452.8157 kcal/mol, -388.0222 kcal/mol, and -323.8843 kcal/mol, respectively. This binding was facilitated through various interactions such as electrostatic forces, π-π interactions, hydrogen bonds, and non-covalent interactions, resulting in potential anti-inflammatory properties. Furthermore, cell experiments using RAW264.7 macrophages demonstrated that these peptides effectively suppressed nitric oxide production in a dose-dependent manner. Additionally, they reduced the production of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1β (IL-1β), inducible iNOS, and cell apoptosis. In conclusion, this study presents a novel approach for developing plant-based mycoproteins and a new source for discovering food-derived bioactive peptides., Competing Interests: Declaration of competing interest The authors assert that they have no identifiable conflicting financial interests or personal relationships that might have influenced the findings reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Lonicera japonica Thunb.,commonly referred to as Caprifolium japonicum (Thunb.) Dum. Cours.,is a perennial herb classified under the caprifoliaceae family. It is utilized worldwide as a medicinal plant and also serves as food source and an ornamental plant. Lonicera japonica Thunb. polysaccharides (LJP) constitute one of its primary components, demonstrating a wide range of biological activities including anti-inflammatory, antioxidant, immunomodulatory, anti-Alzheimer's, anti-diabetic, and anti-cancer effects. This paper reviews and summarizes recent research advancements on the extraction, purification, structural characteristics, and biological activities of LJP, offering a valuable foundation and up-to-date insights for the continued development and application of LJP in pharmaceutical and functional food sectors., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Oxidative stress, inflammation, and bacterial infection are critical barriers to wound healing. In this work, a composite wound dressing was designed to promote wound healing and reduce complications. A hydrogel with antibacterial, anti-inflammatory, and antioxidant properties was prepared by crosslinking chitosan (CS) and oxidized konjac glucomannan with Mg 2+ . We named the prepared hydrogel CPO/Mg 2+ . The proposed hydrogel demonstrated a significant capacity for promoting wound healing. Experimental results indicate that the CPO/Mg 2+ composite hydrogel exhibits a bacteriostatic rate of over 95 % against S. aureus and P. aeruginosa. Furthermore, CPO/Mg 2+ reduced oxidative damage to L929 cells in an H 2 O 2 -induced ROS microenvironment and promoted the polarization of macrophage M2. In vivo full-thickness skin defect experiments revealed that the CPO/Mg 2+ composite hydrogel enhances collagen deposition and angiogenesis, achieving a closure rate of over 95 % for infected wounds within 14 days. This novel composite hydrogel offers an effective strategy for the repair of infected wounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Natural polysaccharides have been recognized as major bioactive components in skincare and wound care products. In this study, the skincare benefits and self-healing properties of Lignosus rhinocerotis polysaccharides (LRP) and its degraded products (DLRP-1, DLRP-2 and DLRP-3) by ultrasound assisted H 2 O 2 /Vc treatment (U-H/V) at different ultrasonic intensity (28.14, 70.35, and 112.56 W/cm 2 ) were investigated. U-H/V altered the internal crystalline structure and microstructure of LRP, and enhanced the thermal stability. Due to the breakage of molecular chains after U-H/V, the moisture absorption of LRP was enhanced but the moisturizing property showed a different degree of reduction. U-H/V significantly improved the antioxidant, anti-tyrosinase and anti-inflammatory activities of LRP. Furthermore, the results of enzyme kinetic studies showed a mixed competitive-noncompetitive inhibition of tyrosinase activity by DLRP-3 and the inhibition constant of DLRP-3 on tyrosinase was 2.97 mg/mL. The apparent viscosity of LRP dispersions showed a first increasing followed by decreasing trend as ultrasonic intensity rose. U-H/V enhanced the viscoelastic properties of LRP gels without destroying their self-healing properties. This findings reveal that U-H/V is beneficial for improving the skincare efficacy of LRP, providing a theoretical foundation for the applicability of LRP in wound dressings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The present work describes the development of silk fibroin (SF)/chitosan (CS)-based porous composite anal fistula scaffold (SCAFS) with anti-inflammatory and healing functions. The SCAFS comprises an inner layer made from degummed silk fiber using a vertical braiding machine, and an outer layer created by freeze-drying a mixture of short SF fibers and curcumin (CUR)/5-aminosalicylic acid (5-ASA) loaded SF/CS solution. Results revealed that the SCAFS has high porosity of 42.4 %, remarkable water absorption rate of 370.5 %, robust dry/wet compression resistance of 12.28 ± 2.61 N/3.08 ± 0.43 N. The in vitro & in vivo biocompatibility and anti-inflammatory effect of SCAFS were further examined. The expression of pro-inflammatory cytokine TNF-α, anti-inflammatory cytokine IL-10, CD31 and CD68 was determined by immunohistochemistry (IHC) staining, H&E staining, Immunofluorescence (IF) staining and Masson assay. The results showed that the scaffolds possess a sustainable drug release above 400 h, better biocompatibility and anti-inflammatory effect than the control groups (p < 0.05). Thus, the SCAFS has potential application in the treatment of Crohn's disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Inflammation and reactive oxygen species (ROS) production often accompany the repair of severe skin wounds, and the management of wounds has always been a clinical challenge, so the design of a hydrogel wound dressing with antioxidant and anti-inflammatory properties is of significant importance. This work incorporated strontium ranelate (SrR) into the keratin/hyaluronic acid (K/HA) hydrogel, which could scavenge ROS and reduce inflammation. The optimized hydrogel exhibits large pore size (217.2 μm), high porosity (57 %), high swelling rate (1759.52 %), and an elastic modulus (3.41 kPa). In the in vitro study, incorporating SrR into hydrogel effectively inhibited oxidative damage in mouse fibroblasts (L929) and improved anti-inflammatory effect in RAW264.7 cells stimulated by lipopolysaccharide. The in vivo study showed that, compared with the control group, the expression of ROS, IL-6 and TNF - α in the K/HA/0.5 mM SrR group were significantly reduced to 31.6 %, 39.7 % and 61.1 %, respectively. The in vivo evaluation in a full-thickness wound defect model demonstrated that K/HA/0.5 mM SrR hydrogel promotes wound healing by attenuating ROS levels, reducing inflammation, and promoting microangiogenesis. In summary, the excellent ROS scavenging and anti-inflammatory properties of SrR make the K/HA/SrR hydrogel a promising and effective strategy for wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ficus carica (F. carica), commonly referred to as the fig tree, has received considerable attention due to its delectable and nutritious fruits. F. carica polysaccharides (FPs) are one of the key bioactive constituents of F. carica, demonstrating various biological activities such as antioxidative, immunomodulatory, anti-inflammatory, and antitumor effects, among others. Nevertheless, the extraction and purification techniques for FPs still require innovations to address their structural characteristics in order to elucidate the intricate mechanisms affecting their biological activities. Given this, the current review systematically summarizes the recent advancements in FPs, covering extraction, purification, structural characteristics, bioactivities, structure-activity relationships (SARs), current applications, challenges and future prospects. The composition of FPs predominantly includes Glu, Gal, and Rha, with a broad molecular weight distribution (ranging from 21.9 kDa to 6890 kDa). The SARs analysis suggests that the bioactivities of FPs are closely linked to their monosaccharide composition, molecular weight, uronic acid content, and configuration characteristics, underscoring the significant role of FPs in driving the development of novel bioactive compounds in the health, food, and medical sectors. In conclusion, this review would contribute the valuable research insights and provide the updated information to foster the advancement of FPs for diverse therapeutic and industrial applications., Competing Interests: Declaration of competing interest The authors declared that there were no competing financial interests or personal relationships., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A miscellaneous polysaccharide, PAP55-3-1, with a molecular weight of 23.03 kDa, was isolated from Periplaneta americana through extraction with dilute alkali solution, ethanol precipitation, and column chromatography purification. Structural analysis shows that PAP55-3-1 is mainly composed of five monosaccharides: galactosamine hydrochloride, glucosamine hydrochloride, galactose, glucose and mannose. Its main glycosidic bonds are: Manp-(1→, Galp-(1→, →3)-Galp-(1→, →3,6)-Manp-(1→, →2,6)-Manp-(1→, →6)-Manp-(1→, →4)-Galp-(1→, →6-Glcp-(1→, →6)-Galp-(1→, →2)-Manp-(1 →, →3,4)-Glcp-(1→, →3,6)-Galp-(1→. In vitro experiments demonstrated that PAP55-3-1 can effectively inhibit reactive oxygen species (ROS) and O 2 - production following H 2 O 2 - induction. After H 2 O 2 - induction, HIF-1α (hypoxia-inducible factor) was translocated in mitochondria PAP55-3-1 increased localization of HIF-1α was located on mitochondria to maintain the stability of mitochondrial function stability, thereby effectively inhibiting H 2 O 2 -induced mitochondrial oxidative damage. Additionally, PAP55-3-1 inhibited the M1 polarization of macrophages stimulated by H 2 O 2 and promoted the phenotype polarization of macrophages from M1 to M2, displaying anti-inflammatory and pro-repair properties. In vivo experimental results indicated that PAP55-3-1 promoted wound healing in mice. Immunohistochemical experiments revealed a reduction in CD68 expression and increase in CD206 expression in both positive and the high-dose polysaccharide group control group. This further demonstrated that PAP55-3-1 promotes the phenotype polarization of macrophages from M1 to M2, exerting anti-inflammatory and wound-healing activities., Competing Interests: Declaration of competing interest The authors declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In this study, a novel camellia oil composite oleogel (SX@G-CO) was prepared by a combination of direct dispersion and emulsion-templated methods using polysaccharides (sodium alginate and xanthan gum, ratio in 4:6) as oleogelators and glycerol monolaurate (GML, 7 wt%) as gel-enhancer. The comparative experiments revealed that the polysaccharides could effectively enhance the densification of the three-dimensional network structure of the oleogel through hydrogen bonding and electrostatic interactions, and significantly improve its thermal stability, rheological properties (adhesive strength 49,243.6 mPa•s, viscosity recovery rate 94.6 %) and oil binding capacity (80.6 %). The introduction of GML further enriched the crystal diversity of the oleogel and imparted excellent antimicrobial ability (nearly 100 % inhibition effect on E.coli). Furthermore, the in vitro experiments demonstrated that the synergistic effect of polysaccharides and GML significantly enhanced the anti-inflammatory, antioxidant, cell migration and proliferation abilities of SX@G-CO oleogel compared with GML-CO and SX-CO oleogels. In addition, SX@G-CO oleogel has also been demonstrated to effectively promote full-thickness burn healing in mice by reducing bacterial infection and inflammatory response, regulating free radical levels, and promoting neovascularization in vivo, with effects comparable to marketed ointment. SX@G-CO oleogel as a bioactive molecule-polysaccharides composite has potential clinical application in burn wound repair., Competing Interests: Declaration of competing interest The authors declare that there is no potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We investigated the antioxidant and anti-inflammatory properties of Lacticaseibacillus rhamnosus Ram12-derived EPSRam12 in a D-galactose-induced liver injury mouse model. Initially, EPSRam12 was characterized for its composition, molecular weight, and structural features. It was then administered orally to D-galactose-induced mice (which had received an intraperitoneal injection of D-galactose, 100 mg/kg body weight) at doses of 25 mg/kg (low dose) and 50 mg/kg (high dose) for 45 days. After treatment, biochemical markers, antioxidant status, cytokine levels, and liver inflammatory gene expression were evaluated. The results showed that EPSRam12 was a branched chain heteropolysaccharide comprising mannose, rhamnose, and arabinose monosaccharides with molecular weight of 2.6 million Daltons. EPSRam12, with its unique structural features such as hydroxyl and methyl groups, glycosidic bonds, and functional groups like carboxylates and sulfates, demonstrated promising bioactive properties. Administering EPSRam12 to D-galactose-induced mice resulted in a significant increase in antioxidant enzyme activity and a reduction in oxidative stress indicators. Additionally, it exhibited anti-inflammatory effects by modulating cytokine levels, lowering pro-inflammatory markers, and inhibiting key inflammatory pathways in the liver in a dose-dependent manner. Our findings underscore the potential of EPSRam12 as an effective antioxidant and anti-inflammatory agent, with promising applications in functional foods and pharmaceuticals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)