Dental Pulp Stem Cell Lysate-Based Hydrogel Improves Diabetic Wound Healing via the Regulation of Anti-Inflammatory Macrophages and Keratinocytes.

The prolonged existence of chronic wounds heightens the risk of patients experiencing chronic pain, necrosis, and amputation. Dental pulp stem cells (DPSCs) have garnered attention due to their potential immunomodulatory and tissue repair regenerative effects in the management of chronic wounds. However, stem-cell-based therapy faces challenges such as malignant differentiation, immune rejection, and long-term effectiveness. To overcome these challenges, we proposed a chronic wound therapy using a hydrogel derived from human-originated dental pulp stem cell lysate (DPSCL). Our data indicate that, with the degradation of the dental pulp stem cell lysate-based hydrogel (DPSCLH), the slowly released cell lysates recruit anti-inflammatory M2 macrophages and promote the proliferation, migration, and keratinization of HacaT cells. In addition, in vivo studies revealed that DPSCLH avoids immune rejection reactions and induces a long-term accumulation of endogenous M2 macrophages. In a mouse model of diabetic wounds, DPSCLH effectively modulates the inflammatory microenvironment around diabetic wounds, promotes the formation of the stratum corneum, and facilitates the healing of wounds, thus holding tremendous potential for the treatment of diabetic wounds.

Allyl isothiocyanate suppressed periodontal tissue destruction in mice via bacteriostatic and anti-inflammatory activities against Porphyromonas gingivalis.

OBJECTIVES: Allyl isothiocyanate (AITC) is a phytochemical that is abundantly present in cruciferous vegetables, such as wasabi and mustard. Among its pharmacological properties, it demonstrates anticancer, antifungal, and anti-inflammatory activities. This study aimed to investigate the functions of AITC against periodontopathic bacteria and its effects on a mouse model of periodontitis. DESIGN: The antimicrobial and antibiofilm functions of AITC were assessed against Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus mitis. To clarify its anti-inflammatory effects, macrophage-like cells from THP-1 were stimulated with P. gingivalis lipopolysaccharide (LPS), and the release of inflammatory cytokines was analyzed by ELISA. Experimental periodontitis was induced in 9-week-old mice by ligation and oral infection of P. gingivalis, and AITC was injected into the gingiva once daily for 8 days. Alveolar bone resorption was evaluated by measuring the exposed root area. Gene expressions in the periodontal tissue were analyzed via qPCR. RESULTS: AITC exerted weak bacteriostatic effects against P. gingivalis, inhibiting biofilm formation. AITC also impeded the production of interleukin-6 and tumor necrosis factor-α induced by P. gingivalis LPS. Additionally, transient receptor potential ankyrin 1(TRPA1) channel agonist inhibited the anti-inflammatory effects of AITC. In vivo, AITC inhibited alveolar bone destruction and decreased the gene transcription of Il6 in the periodontal tissue. CONCLUSION: AITC exerted weak bacteriostatic and anti-inflammatory effects against P. gingivalis, reducing alveolar bone destruction and suppressing the inflammatory response in experimental periodontitis. Therefore, AITC may serve as a valuable adjunct in controlling periodontal disease.

Qisheng wan decoction alleviates the inflammation of CCI rats via TRP channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Qisheng wan decoction (QWD), a traditional Chinese medicine, has promising potential anti-inflammatory effects against neuropathic pain (NP). However, its valid ingredients and specific anti-inflammatory mechanisms are still unclear. AIM OF THE STUDY: This study aimed to identify the active ingredients of QWD responsible for its anti- inflammatory effect by combining liquid chromatography with network pharmacology, and to explore its anti- inflammatory mechanism by chronic constriction injury (CCI) model rats. MATERIALS AND METHODS: The UHPLC-Q Exactive Orbitrap-MS technique was used to identify the active ingredients of QWD. The potential ingredients of QWD, which targeted to the pathways of treating NP, were performed by network pharmacology, molecular docking and molecular dynamics simulations. After CCI rats-induced NP model operation, QWD (5.6 g/kg/d, 11.2 g/kg/d, 22.4 g/kg/d) and Pregabalin (10g/kg/d) as positive controls, were administered to the rats for 7 days. The behaviors of the different groups were tested at 0, 1, 3, 5, 7, 12 days, respectively. And the inflammatory factor including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) was detected by ELISA. Meantime, the inflammation of the sciatic nerve was evaluated by the hematoxylin-eosin staining. Ionized calcium-binding adapter molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) were detected by immunohistochemistry. Moreover, the expressions of TRPA1, TRPV1, TRPV2, TRPV3, TRPV4, TRPM8, and P38 mitogen-activated protein kinase (MAPK) were tested by RT-PCR, western blot, and immunohistochemistry. RESULTS: After screening by the liquid chromatography and network pharmacology approach, seventy ingredients of QWD were identified, and seven core targets including oncogene tyrosine-protein kinase (SRC), mitogen-activated protein kinase 3 (MAPK3), signal transducer and activator of transcription 1 (STAT1), protein-serine-threonine kinase 1 (AKT1), mitogen-activated protein kinase 1 (MAPK1), TNF-α, and IL-6 were confirmed. Six active ingredients exhibited binding energies less than -5 kcal/mol, and the complexes were structurally stable within 50 ns. Pathway analysis indicated that transient receptor potential (TRP) channels were mainly responsible for anti-inflammatory mediator regulation. Compared with the CCI group, the behavioral tests showed that QWD-L, QWD-M, and QWD-H group alleviated mechanical, thermal and cold hyperalgesia (p<0.05). HE staining results found out QWD-L, QWD-M, and QWD-H group decreased the inflammation of the sciatic nerve (p<0.05). Similarly, compared with the CCI group, the serum level of TNF-α and IL-6 of QWD groups decreased conformably (p<0.05). This reduction was downtrend with the inhibition of Iba-1, GFAP, and the TRP channel signaling pathway and p38 MAPK. CONCLUSIONS: This study provides a primary investigation of the composition of QWD for its anti- inflammation effect and its molecular mechanism in CCI model rats. And this therapeutic efficacy of QWD was achieved by decreasing the inflammation. QWD also inhibited the level TNF-α and IL-6 and decreasing the activation of Iba-1 and GFAP in glia. And this anti-inflammation mechanism involved in inhibiting the TRPA1, TRPV1, TRPV2, TRPV4, and TRPM8 and p38 MAPK signaling pathways. These findings provide a scientific and theoretical basis for the prevention and treatment of NP with QWD.

Propionibacterium freudenreichii MJ2-derived extracellular vesicles inhibit RANKL-induced osteoclastogenesis and improve collagen-induced rheumatoid arthritis.

Rheumatoid arthritis causes excessive bone loss by stimulating osteoclast differentiation. Extracellular vesicles are valuable disease markers, conveyors of distant cell-to-cell communication, and carriers for drug delivery. The aim of this study was to investigate the anti-osteoclastogenic effects of extracellular vesicles derived from dairy Propionibacterium freudenreichii MJ2 (PFEVs) and the improvement effect of PFEVs on collagen-induced arthritis (CIA) animal model. PFEVs were observed by scanning electron microscopy, transmission electron microscopy, nanoparticle tracking analysis, and LC-MS/MS. The inhibitory activity of PFEVs against receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation was investigated in RAW 264.7 cells. PFEVs significantly decreased the expression levels of genes and proteins related to osteoclast differentiation. PFEVs decreased RANK-RANKL binding. In a CIA mouse model, PFEVs treatment significantly reduced arthritis scores and collagen-specific immunoglobulins. PFEVs treatment also reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines. The anti-inflammatory effects were confirmed by H&E staining, and PFEVs treatment inhibited osteoclastogenesis in the CIA mouse model. In conclusion, PFEVs inhibited osteoclast differentiation by inhibiting RANK-RANKL signaling, thereby decreasing the expression of osteoclast differentiation-related genes. PFEVs also improved collagen-induced arthritis by inhibiting inflammation and osteoclastogenesis.

Functionalized metal oxide nanoparticles: A promising intervention against major health burden of diseases.

Metal oxide nanoparticles (MONPs) is one of the most effective materials for medical applications with their substantial surface metallic ions and high surface area-volume ratio. Over decades, MONPs have been considered potential treatments due to their demonstrated ability and reactivity to target diverse cellular signaling pathways implicated in antimicrobial effects, as well as in the amelioration of oxidative stress, inflammation, cancer progression, and glucose together with lipid dysregulation. Based on their unique characteristics, MONPs have shown to be biodegradable and biocompatible vehicles for drugs, which have recently been applied in drug delivery as nanocarriers to enhance their delivery capacity for mechanistic membrane transport. However, little is known about the precise cellular responses, molecular mechanisms, and potential use of MONPs in the medical field. This review emphasizes on elaborating the biochemical reactivities of MONPs on molecular and cellular reactions, highlighting the physiological responses, mechanisms of action, certain drawbacks, and remediation of these functionalized materials. The significant goal of this literature is to shed light on the new perspectives of MONPs in pre-clinical application to pursue for clinical research as alternative-personalized medicines to prevent individuals from drastic diseases.

In situ photocrosslinkable hydrogel treats radiation-induced skin injury by ROS elimination and inflammation regulation.

The clinical management of radiation-induced skin injury (RSI) poses a significant challenge, primarily due to the acute damage caused by an overabundance of reactive oxygen species (ROS) and the ongoing inflammatory microenvironment. Here, we designed a dual-network hydrogel composed of 5 % (w/v) Pluronic F127 diacrylate and 2 % (w/v) hyaluronic acid methacryloyl, termed the FH hydrogel. To confer antioxidant and anti-inflammation properties to the hydrogel, we incorporated PVP-modified Prussian blue nanoparticles (PPBs) and resveratrol (Res) to form PHF@Res hydrogels. PHF@Res hydrogels not only exhibited multiple free radical scavenging activities (DPPH, ABTS), but also displayed multiple enzyme-like activities (POD-, catalase). Meanwhile, PHF@Res-2 hydrogels significantly suppressed intracellular ROS and promoted the migration of fibroblasts in a high-oxidative stress environment. Moreover, in the RSI mouse model, the PHF@Res-2 hydrogel regulated inflammatory factors and collagen deposition, significantly reduced epithelial hyperplasia, promoted limb regeneration and neovascularization, and accelerated wound healing, outperforming the commercial antiradiation formulation, Kangfuxin. The PHF@Res-2 hydrogel dressing shows great potential in accelerating wound healing in RSI, offering tremendous promise for clinical wound management and regeneration.

Polyphenols with anti-inflammatory activity isolated from the whole herbs of Delphinium forrestii var. Viride.

Delphinium belongs to Ranunculaceae, which is widely distributed in Northwest China. In folk, this genus of plants has analgesic, anti-inflammatory, and insecticidal effects. By studying non-alkaloid components in the whole herbs of Delphinium forrestii, we obtained a total of 11 compounds (1-11), including five new (1-5) and six known polyphenols (6-11). On the basis of chemical evidences and spectral data analysis (UV, Optical rotation data, 1D/2D-NMR and HR-ESI-MS), the structures of new compounds were elucidated. The inhibitory effect of compounds 1-11 on lipopolysaccharide (LPS) induced NO production in RAW 264.7 cells was detected. Compounds 4 and 11 showed significant inhibitory effects. This study indicated the presence of compounds with good anti-inflammatory activity among non-alkaloid components in the whole herbs of Delphinium forrestii.

Evaluation of Quinoline-Related Carboxylic Acid Derivatives as Prospective Differentially Antiproliferative, Antioxidative, and Anti-Inflammatory Agents.

The higher prevalence of cancer and the unmet need for antioxidant/anti-inflammatory chemotherapeutic compounds with little side effect are of utmost importance. In addition, the increased likelihood of failure in clinical trials along with increasing development costs may have diminished the range of choices among newer drugs for clinical use. This has dictated the necessity to seek out novel medications by repurposing as it needs less time, effort, and resources to explore new uses of a current or unsuccessful medication. In this study, we examined the biological activity of 10 potential quinoline derivatives. Given the half-maximal inhibitory concentration (IC50 value) in lipopolysaccharide (LPS) induced inflammation of RAW264.7 mouse macrophages, all commercial FQs and selected quinolines (quinoline-4-carboxlic and quinoline-3-carboxylic acids) exerted impressively appreciable anti-inflammation affinities versus classical NSAID indomethacin without related cytotoxicities in inflamed macrophages. Conversely, all 14 tested compounds lacked antioxidative DPPH radical scavenging capacities as compared to ascorbic acid. Gemifloxacin, considerably unlike markets FQs, indomethacin and quinoline derivatives, exerted exceptional and differential antiproliferation propensities in colorectum SW480, HCT116, and CACO2, pancreatic PANC1, prostate PC3, mammary T47D, lung A375, and melanoma A549 adherent monolayers using the sulforhodamine B colorimetric method versus antineoplastic cisplatin. All quinoline derivatives and gemifloxacin alike, but not levofloxacin, ciprofloxacin, or indomethacin, displayed substantially selective viability reduction affinities in prolonged tumor incubations of cervical HELA and mammary MCF7 cells. Specifically kynurenic acid (hydrate), quinoline-2-carboxylic acid, quinoline-4-carboxylic acid, quinoline-3-carboxylic acid, and 1,2-dihydro-2-oxo-4-quinoline carboxylic acids possessed the most remarkable growth inhibition capacities against mammary MCF7 cell line, while quinoline-2-carboxylic acid was the only quinoline derivative with significant cytotoxicity on cervical HELA cancer cells. It is highly speculated that chelation with divalent metals via co-planarity with close proximity of the COOH and the N atom could have the potential molecular mechanism for optimally promising repurposed pharmacologies. Conclusively, this study revealed the considerably profound repurposed duality of cytotoxicity and anti-inflammation pharmacologies of quinoline derivatives. Activity-guided structural modifications of the present nuclear scaffolds can be inherently linked to the betterment and enhancement of their repurposed pharmacologies.

Dual Functionality of Papaya Leaf Extracts: Anti-Coronavirus Activity and Anti-Inflammation Mechanism.

Papaya leaves have been used as food and traditional herbs for the treatment of cancer, diabetes, asthma, and virus infections, but the active principle has not been understood. We hypothesized that the anti-inflammatory activity could be the predominant underlying principle. To test this, we extracted papaya leaf juice with different organic solvents and found that the ethyl acetate (EA) fraction showed the most outstanding anti-inflammatory activity by suppressing the production of nitric oxide (NO, IC50 = 24.94 ± 2.4 µg/mL) and the expression of pro-inflammatory enzymes, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), and cytokines including interleukins (IL-1ß and IL-6), and a tumor necrosis factor (TNF-α) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Transcriptomic analysis and Western blot results revealed its anti-inflammatory mechanisms were through the MAPK signaling pathway by inhibiting the phosphorylation of ERK1/2, JNKs, and p38 and the prevention of the cell surface expression of TLR4. Furthermore, we discovered that the EA fraction could inhibit the replication of alpha-coronavirus (HCoV-229E) and beta-coronavirus (HCoV-OC43 and SARS-CoV-2) and might be able to prevent cytokine storms caused by the coronavirus infection. From HPLC-QTOF-MS data, we found that the predominant phytochemicals that existed in the EA fraction were quercetin and kaempferol glycosides and carpaine. Counter-intuitively, further fractionation resulted in a loss of activity, suggesting that the synergistic effect of different components in the EA fraction contribute to the overall potent activity. Taken together, our results provide preliminary evidence for papaya leaf as a potential anti-inflammatory and anti-coronavirus agent, warranting further study for its use for human health promotion.

Preparing a Phytosome for Promoting Delivery Efficiency and Biological Activities of Methyl Jasmonate-Treated Dendropanax morbifera Adventitious Root Extract (DMARE).

(1) Background: Methyl jasmonate-treated D. morbifera adventitious root extract (MeJA-DMARE), enriched with phenolics, has enhanced bioactivities. However, phenolics possess low stability and bioavailability. Substantial evidence indicates that plant extract-phospholipid complex assemblies, known as phytosomes, represent an innovative drug delivery system. (2) Methods: The phytosome complex was created by combining MeJA-DMARE with Soy-L-α-phosphatidylcholine (PC) using three different ratios through two distinct methods (co-solvency method: A1, A2, and A3; thin-layer film method: B1, B2, and B3). (3) Results: Initial evaluation based on UV-Vis, entrapment efficiency (EE%), and loading content (LC%) indicated that B2 exhibited the highest EE% (79.98 ± 1.45) and LC% (69.17 ± 0.14). The phytosome displayed a spherical morphology with a particle size of 210 nm, a notably low polydispersity index of 0.16, and a superior zeta potential value at -25.19 mV. The synthesized phytosome exhibited superior anti-inflammatory activities by inhibiting NO and ROS production (reduced to 8.9% and 55.1% at 250 µg/mL) in RAW cells and adjusting the expression of related inflammatory cytokines; they also slowed lung tumor cell migration (only 2.3% of A549 cells migrated after treatment with phytosomes at 250 µg/mL), promoting ROS generation in A549 cell lines (123.7% compared to control) and stimulating apoptosis of lung cancer-related genes. (4) Conclusions: In conclusion, the MeJA-DMARE phytosome offers stable, economically efficient, and environmentally friendly nanoparticles with superior inflammation and lung tumor inhibition properties. Thus, the MeJA-DMARE phytosome holds promise as an applicable and favorable creation for drug delivery and lung cancer treatment.

Syntheses, crystal structures of copper (II)-based complexes of sulfonamide derivatives and their anticancer effects through the synergistic effect of anti-angiogenesis, anti-inflammation, pro-apoptosis and cuproptosis.

Three novel copper(II)-based complexes Cu-1, Cu-2, and Cu-3 containing sulfamethoxazole or sulfamethazine ligand were obtained, and their single structures were characterized. Both Cu-1 and Cu-3 show a broad spectrum of cytotoxicity than Cu-2, and Cu-1 is more cytotoxic than Cu-3. What's interesting is that Cu-1 can exhibit obvious inhibitory effect on the growth of human triple-negative breast cancer in vivo and vitro through anti-proliferative, anti-angiogenic, anti-inflammatory, pro-apoptotic and cuproptotic synergistic effects. Though Cu-3 shows no significant cytotoxicity against MDA-MB-231 cells, it can significantly inhibit the growth of SKOV3 cells in vitro by down-regulating the expression of some key proteins in the VEGF/VEGFR2 signaling pathway and the expression of some pro-inflammatory cytokines, and by disrupting the balance of intracellular reactive oxygen species levels.

Improved solubility and bioavailability of cyclolinopeptides by diacylglycerol in the ß-cyclodextrin Pickering emulsions.

Cyclolinopeptides (CLs) have anti-inflammatory, anti-osteoporosis, and anti-tumor effects, however, low water and oil solubility greatly limit their application. Herein, CLs-loaded ß-cyclodextrin (ß-CD) emulsions were prepared with different oil phases. The in vitro digestibility, cellular absorption, and anti-inflammatory effects were evaluated. Camellia oil diacylglycerol (CO DAG) showed enhanced dissolving ability for CLs due to high polarity. ß-CD formed inclusion complexes with DAG through hydrogen bond and the emulsions showed smaller size and higher physical stability with 50 % (w/w) oil. The in vitro digestibility of the DAG emulsion was increased and the CLs' bioavailability was 13.6-fold higher than CLs in oil. The CLs-loaded Pickering emulsion digesta exhibited a higher nitric oxides (NO) inhibition rate (58.62 %) and Caco-2 cell penetration (3.09 × 10-6 cm/s). Therefore, emulsion formulated with ß-cyclodextrin and DAG can effectively improve the solubility and bioavailability of CLs, which has significant potential for application in functional foods and pharmaceutical industry.

Cimicifuga heracleifolia kom. Attenuates ulcerative colitis through the PI3K/AKT/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cimicifuga heracleifolia Kom. (C. heracleifolia) has demonstrated efficacy in treating gastrointestinal disorders, including splenasthenic diarrhea. Ulcerative colitis (UC), a chronic inflammatory bowel disease, shares similarities with splenasthenic diarrhea. However, the pharmacological effects of C. heracleifolia on UC and the underlying mechanisms remain unexplored. AIM OF THE STUDY: The present study investigates the therapeutic potential and mechanisms of C. heracleifolia in UC. METHODS: Initially, network pharmacology analysis, encompassing ingredient screening, target prediction, protein-protein interaction (PPI) network analysis, and enrichment analysis, was employed to predict the mechanisms of C. heracleifolia. The findings were further validated using transcriptomics and functional assays in a dextran sulfate sodium (DSS)-induced UC model. Additionally, bioactive compounds were identified through surface plasmon resonance (SPR) analysis, molecular docking, and cell-based assays. RESULTS: A total of 52 ingredients of C. heracleifolia were screened, and 32 key targets were identified within a PPI network comprising 285 potential therapeutic targets. Enrichment analysis indicated that the anti-UC effects of C. heracleifolia are mediated through immune response modulation and the inhibition of inflammatory signaling pathways. In vivo experiments showed that C. heracleifolia mitigated histological damage in the colon, reduced the expression of phosphorylated Akt1, nuclear factor-kappa B (NF-κB) p65, and inhibitor of Kappa B kinase α/ß (IKKα/ß), suppressed the content of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and enhanced the expression of tight junction proteins. Moreover, cimigenoside, caffeic acid, and methyl caffeate were identified as the bioactive constituents responsible for the UC treatment effects of C. heracleifolia. CONCLUSIONS: In summary, this study is the first to demonstrate that C. heracleifolia exerts therapeutic effects on UC by enhancing the intestinal mucosal barrier and inhibiting the phosphatidylinositol 3-kinase (PI3K)/AKT/NF-κB signaling pathway. These findings offer valuable insights into the clinical application of C. heracleifolia for UC management.

Hair Growth-Promoting Effect of Hydrangea serrata (Thunb.) Ser. Extract and Its Active Component Hydrangenol: In Vitro and In Vivo Study.

With the escalating prevalence of hair loss, the demand for effective hair loss treatment has surged. This study evaluated the effects of hot water extract of Hydrangea serrata (Thunb.) Ser. leaf (WHS) on hair growth, employing cell cultures, mice, and human skin organoid models. Both WHS and hydrangenol were found to enhance 5α-reductase inhibitory activity. WHS and hydrangenol have been shown to stimulate dermal papilla cell (DPC) growth, potentially through factors like keratinocyte growth factor (KGF), fibroblast growth factor 10 (FGF10), and transforming growth factor-ß1 (TGF-ß1). They also elevated the expression levels of keratin genes (K31 and K85) and the ceramide synthase (CerS3) gene, crucial clinical indicators of hair health. Furthermore, they exhibited notable anti-inflammatory and anti-androgenic properties by reducing the levels of tumor necrosis factor-α (TNF-α) and androgen signaling molecules, including androgen receptor (AR) and dickkopf-1 (DKK-1) gene expression. Oral administration of WHS to C57BL/6 mice for 3 weeks confirmed its hair growth-promoting effects, improving hair growth parameters and gene expression without significant changes in hair weight. Additionally, in a human skin organoid model, WHS was found to stimulate hair formation and augment the expression of follicle markers. These findings position WHS as a promising nutraceutical for promoting hair health, as evidenced by its efficacy in both in vitro and in vivo models.

Molecular Mechanism of 5,6-Dihydroxyflavone in Suppressing LPS-Induced Inflammation and Oxidative Stress.

5,6-dihydroxyflavone (5,6-DHF), a flavonoid that possesses potential anti-inflammatory and antioxidant activities owing to its special catechol motif on the A ring. However, its function and mechanism of action against inflammation and cellular oxidative stress have not been elucidated. In the current study, 5,6-DHF was observed inhibiting lipopolysaccharide (LPS)-induced nitric oxide (NO) and cytoplasmic reactive oxygen species (ROS) production with the IC50 of 11.55 ± 0.64 µM and 0.8310 ± 0.633 µM in murine macrophages, respectively. Meanwhile, 5,6-DHF suppressed the overexpression of pro-inflammatory mediators such as proteins and cytokines and eradicated the accumulation of mitochondrial ROS (mtROS). The blockage of the activation of cell surface toll-like receptor 4 (TLR4), impediment of the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 from the mitogen-activated protein kinases (MAPK) pathway, Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) from the JAK-STAT pathway, and p65 from nuclear factor-κB (NF-κB) pathways were involved in the process of 5,6-DHF suppressing inflammation. Furthermore, 5,6-DHF acted as a cellular ROS scavenger and heme-oxygenase 1 (HO-1) inducer in relieving cellular oxidative stress. Importantly, 5,6-DHF exerted more potent anti-inflammatory activity than its close structural relatives, such as baicalein and chrysin. Overall, our findings pave the road for further research on 5,6-DHF in animal models.

The Immobilization of an FGF2-Derived Peptide on Culture Plates Improves the Production and Therapeutic Potential of Extracellular Vesicles from Wharton's Jelly Mesenchymal Stem Cells.

The skin is an essential organ that protects the body from external aggressions; therefore, damage from various wounds can significantly impair its function, and effective methods for regenerating and restoring its barrier function are crucial. This study aimed to mass-produce wound-healing exosomes using a fragment of the fibroblast growth factor 2 (FGF2)-derived peptide (FP2) to enhance cell proliferation and exosome production. Our experiments demonstrated increased cell proliferation when Wharton's jelly mesenchymal stem cells (WJ MSCs) were coated with FP2. Exosomes from FP2-coated WJ MSCs were analyzed using nanoparticle-tracking analysis, transmission electron microscopy, and Western blotting. Subsequently, fibroblasts were treated with these exosomes, and their viability and migration effects were compared. Anti-inflammatory effects were also evaluated by inducing pro-inflammatory factors in RAW264.7 cells. The treatment of fibroblasts with FP2-coated WJ MSC-derived exosomes (FP2-exo) increased the expression of FGF2, confirming their wound-healing effect in vivo. Overall, the results of this study highlight the significant impact of FP2 on the proliferation of WJ MSCs and the anti-inflammatory and wound-healing effects of exosomes, suggesting potential applications beyond wound healing.

"Therapeutic advancements in nanomedicine: The multifaceted roles of silver nanoparticles".

Nanotechnology has the advantages of enhanced bioactivity, reduced toxicity, target specificity, and sustained release and NPs can penetrate cell membranes. The small size of silver nanoparticles, AgNPs, large surface area, and unique physicochemical properties contribute to cell lysis and increased permeability of cell membranes used in the field of biomedicine. Functional precursors integrate with phytochemicals to create distinctive therapeutic properties and the stability of the nanoparticles can be enhanced by Surface coatings and encapsulation methods, The current study explores the various synthesis methods and characterization techniques of silver nanoparticles (AgNPs) and highlights their intrinsic activity in therapeutic applications, Anti-cancer activity noted at a concentration range of 5-50 µg/ml and angiogenesis is mitigated at a dosage range of 10-50 µg/ml, Diabetes is controlled within the same concentration. Wound healing is improved at concentrations of 10-50 µg/ml and with a typical range of 10-08 µg/ml for bacteria with antimicrobial capabilities. Advancement of silver nanoparticles with a focus on the future use of AgNPs-coated wound dressings and medical devices to decrease the risk of infection. Chemotherapeutic drugs can be administered by AgNPs, which reduces adverse effects and an improvement in treatment outcomes. AgNPs have been found to improve cell proliferation and differentiation, making them beneficial for tissue engineering and regenerative medicine. Our study highlights emerging patterns and developments in the field of medicine, inferring potential future paths.

Biomimetic Nanomodulator Regulates Oxidative and Inflammatory Stresses to Treat Sepsis-Associated Encephalopathy.

Sepsis-associated encephalopathy (SAE) is a devastating complication of sepsis, affecting approximately 70% of patients with sepsis in intensive care units (ICU). Although the pathophysiological mechanisms remain elusive, sepsis is typically accompanied by systemic inflammatory response syndrome (SIRS) and hyper-oxidative conditions. Here, we introduce a biomimetic nanomodulator (mAOI NP) that specifically targets inflammation site and simultaneously regulates oxidative and inflammatory stresses. mAOI NPs are constructed using metal-coordinated polyphenolic antioxidants (tannic acid) and flavonoid quercetin, which are then coated with macrophage membrane to enhance pharmacokinetics and enable SAE targeting. In a cecal ligation and puncture (CLP)-induced severe sepsis model, mAOI NPs effectively mitigate oxidative stress by purging reactive oxygen species, repairing mitochondrial damage and activating the Nrf2/HO-1 signaling pathway; while polarizing M1 macrophages or microglia toward anti-inflammatory M2 subtype. mAOI NPs potently inhibit sepsis progress, prolong overall survival from 25 to 66% and enhance learning and memory capabilities in SAE mice. Further proteomics analysis reveals that mAOI NPs modulate neurodevelopment processes related to learning and memory formation while also exerting anti-inflammatory and antioxidative effects on brain tissue responses associated with SAE pathology. This study offers significant potential for improving patient outcomes and revolutionizing the treatment landscape for this devastating complication of sepsis.

RVG-peptide-camouflaged iron-coordinated engineered polydopamine nanoenzyme with ROS scavenging and inhibiting inflammatory response for ischemic stroke therapy.

Stroke is one of the most common causes of death and disability. In addition, most neuroprotective agents fail to rescue neurons from cerebral ischemic insults due to their poor ability to penetrate the blood-brain barrier (BBB). Here, the tailored engineered nanoenzyme has been successfully synthesized by coordination-driven co-assembly of dopamine (DA) and iron ion (Fe3+), which is subsequently camouflaged by neuron-specific rabies viral glycoprotein (RVG) peptide to scavenge reactive oxygen species (ROS) and inhibit inflammatory response in damaged neuron for the efficient therapy of ischemic stroke. The resulting nanoenzyme with good biocompatibility, core-shell structure, and suitable diameter can nondestructively cross the BBB and then internalize into the damaged neuron through the camouflaging and homologous targeted strategy of neuron-specific RVG peptide. After intravenous injection into transient middle cerebral artery occlusion (tMCAO) mouse models, nanoenzyme exerted a significant neuroprotective effect, resulting in a 50 % reduction in neurological scores and an approximate 33 % decrease in cerebral infarction volume. Interestingly, such nanoenzyme can eliminate free radicals, reduce neuroinflammation, enhance BBB integrity, improve mitochondrial function, and inhibit neuronal ferroptosis. Taken together, this well-designed nanoenzyme with its excellent biocompatibility and well-understood mechanisms holds promise a robust therapy for ischemic stroke.

Preclinical Evaluation of Protective Effects of Terpenoids Against Nanomaterial-Induced Toxicity: A Meta-Analysis.

Terpenoids, the largest class of natural products, have been demonstrated to confer antioxidant, anti-inflammatory, anti-apoptotic, and antitumor activities. However, whether terpenoids benefit populations exposed to nanomaterials through these mechanisms remains unclear. This meta-analysis was to evaluate the effects of terpenoids in preclinical models with nanomaterial exposure. Electronic database searching identified 39 studies. The meta-analysis by Stata 15.0 showed that terpenoid supplementation significantly improved cell viability and altered oxidative stress (decreased ROS, NO, MDA, and TOC and increased SOD, CAT, GPx, GSH, GSH-Px, and TAC)-, inflammation (decreased IL-6, IL-1ß, TNF-α, NF-κB, monocytes, and increased IL-10)-, apoptosis (reduced Bax, caspase-3, caspase-9, P53, and elevated Bcl-2)-, genotoxic (reduced tail length, % tail DNA, tail moment, DNA fragmentation, chromosomal aberration, and MNPCEs)-, liver function (reduced ALT, AST, and ALP)-, renal function (reduced creatinine, urea, and uric acid)-, reproductive function (increased sperm count, testosterone, Johnsen's score, and number of progeny)-, lipid profile (lower cholesterol, TG, LDL, and higher HDL)-, and carcinogenesis (downregulated AFP and CEA)-related biomarkers induced by nanomaterials. Subgroup analysis indicated that monoterpenoids and tetraterpenoids were particularly effective. Collectively, terpenoids may be a promising candidate for prevention of toxicities caused by nanomaterials.