Antimicrobial, Antioxidant, and Anti-Inflammatory Nanoplatform for Effective Management of Infected Wounds.

Burn wound healing continues to pose significant challenges due to excessive inflammation, the risk of infection, and impaired tissue regeneration. In this regard, an antibacterial, antioxidant, and anti-inflammatory nanocomposite (called HPA) that combines a nanosystem using hexachlorocyclotriphosphazene and the natural polyphenol of Phloretin with silver nanoparticles (AgNPs) is developed. HPA effectively disperses AgNPs to mitigate any toxicity caused by aggregation while also showing the pharmacological activities of Phloretin. During the initial stage of wound healing, HPA rapidly releases silver ions from its surface to suppress bacterial activity. Moreover, these nanoparticles are pH-sensitive and degrade efficiently in the acidic infection microenvironment, gradually releasing Phloretin. This sustained release of Phloretin helps scavenge overexpressed reactive oxygen species in the infected microenvironment area, thus reducing the upregulation of pro-inflammatory cytokines. The antibacterial activity, free radical clearance, and regulation of inflammatory factors of HPA through in vitro experiments are validated. Additionally, its effects using an infectious burn mouse model in vivo are evaluated. HPA is found to promote collagen deposition and epithelialization in the wound area. With its synergistic antibacterial, antioxidant, and anti-inflammatory activities, as well as favorable biocompatibilities, HPA shows great promise as a safe and effective multifunctional nanoplatform for burn injury wound dressings.

Development of a Deep Eutectic Solvent-Assisted Kaempferol Hydrogel: A Promising Therapeutic Approach for Psoriasis-like Skin Inflammation.

Psoriasis is an incurable inflammatory skin disease that is mediated by the immune system. Although kaempferol has been known for its anti-inflammatory, antioxidant, and anticancer properties, its therapeutic effectiveness is often limited due to its poor water solubility and low bioavailability. To address these challenges, we developed a promising kaempferol hydrogel (DK-pGEL) using Pluronic F127 and a deep eutectic solvent (DES) with varying concentrations of kaempferol. In this study, we first evaluated the rheological properties and viscosity of the DK-pGEL hydrogel. The G' of DK-pGEL (∼14 kPa) hydrogels was significantly lower than the control group (∼30 kPa) at 37 °C. The DK-pGEL hydrogel exhibited ideal fluidity and viscosity at 37 °C, as demonstrated by its shear-thinning behavior. Moreover, the DK-pGEL hydrogel showed controlled release characteristics with a drug release of 97.43 ± 5.37 µg/mL over 60 h. Furthermore, in vitro antioxidant experiments revealed that DK-pGEL exhibited significant radical scavenging ability against the DPPH-radical (96.27 ± 0.37%), ABTS-radical (98.11 ± 0.79%), hydroxyl-radical (66.36 ± 1.01%), and superoxide-radical (90.52 ± 0.79%) at a concentration of 250 µg/mL kaempferol. Additionally, DK-pGEL exhibited notable cellular antioxidant effects by inhibiting reactive oxygen species generation. Cell viability assays (CCK8) and live/dead cell assays were conducted to assess the cytotoxicity of DK-pGEL. The results showed that DK-pGEL could effectively inhibit HaCaT cell proliferation without causing significant cytotoxicity. To evaluate the therapeutic potential of DK-pGEL, an imiquimod (IMQ)-induced mouse model of psoriasis-like lesions was employed. Remarkably, the DK-pGEL hydrogel could significantly reduce the psoriasis area and severity index score, improve the histopathology induced by IMQ, and downregulate the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-17A) in the skin tissue. These findings demonstrate that the DES-assisted kaempferol hydrogel holds promise as a topical drug delivery system for psoriasis treatment.

[Shaofu Zhuyu Decoction attenuates fibrosis in endometriosis through regulating PTEN/Akt/mTOR signaling pathway].

The present study aimed to investigate the protective role of Shaofu Zhuyu Decoction(SFZY) against endometriosis fibrosis in mice, and decipher the underlying mechanism through the phosphatase and tensin homolog deleted on chromosome ten(PTEN)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) pathway. Eighty-five BALB/c female mice were randomly assigned into a blank group, a model group, high-, medium, and low-dose SFZY(SFZY-H, SFZY-M, and SFZY-L, respectively) groups, and a gestrinone suspension(YT) group. The model of endometriosis was induced by intraperitoneal injection of uterine fragments. The mice in different groups were administrated with corresponding groups by gavage 14 days after modeling, and the blank group and model group with equal volume of distilled water by gavage. The treatment lasted for 14 days. The body weight, paw withdrawal latency caused by heat stimuli, and total weight of dissected ectopic focus were compared between different groups. The pathological changes of the ectopic tissue were observed via hematoxylin-eosin(HE) and Masson staining. Real-time PCR was employed to measure the mRNA levels of α-smooth muscle actin(α-SMA) and collagen type Ⅰ(collagen-Ⅰ) in the ectopic tissue. The protein levels of PTEN, Akt, mTOR, p-Akt, and p-mTOR in the ectopic tissue were determined by Western blot. Compared with the blank group, the modeling first decreased and then increased the body weight of mice, increased the total weight of ectopic focus, and shortened the paw withdrawal latency. Compared with the model group, SFZY and YT increased the body weight, prolonged the paw withdrawal latency, and decreased the weight of ectopic focus. Furthermore, the drug administration, especially SFZY-H and YT(P<0.01), recovered the pathological and reduced the area of collagen deposition. Compared with the blank group, the modeling up-regulated the mRNA levels of α-SMA and collagen-Ⅰ in the ectopic focus, and such up-regulation was attenuated after drug intervention, especially in the SFZY-H and YT groups(P<0.05,P<0.01). Compared with the blank group, the modeling down-regulated the protein level of PTEN and up-regulated the protein levels of Akt, mTOR, p-Akt, and p-mTOR(P<0.01, P<0.001). Drug administration, especially SFZY-H and YT, restored such changes(P<0.01). SFZY may significantly attenuate the focal fibrosis in the mouse model of endometriosis by regulating the PTEN/Akt/mTOR signaling pathway.

Identification of immune- and autophagy-related genes and effective diagnostic biomarkers in endometriosis: a bioinformatics analysis.

Background: To identify autophagy- and immune-related hub genes affecting the diagnosis and treatment of endometriosis. Methods: Gene expression data were downloaded from the Gene Expression Omnibus (GEO) (GSE11691 and GSE120103 for training, and GSE7305 for validation). By overlapping the differentially expressed genes (DEGs), Weighted gene co-expression network analysis (WGCNA) module genes, and autophagy-related genes (ARGs), and immune-related genes (IRGs) separately, hub genes were identified using the least absolute shrinkage and selection operator (LASSO)and support vector machine recursive feature elimination (SVM-RFE). The hub genes were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A hub gene-prediction model was constructed and assessed using five-fold cross-validation via five supervised machine-learning algorithms: random forest, the sequential minimal optimization (SMO), K-nearest neighbours (IBK), C4.5 decision tree (J48), and logistics regression. The area under the receiver operating characteristic curve (AUC) was adopted to assess the identification ability of characteristic genes. Results: 1,116 DEGs were obtained from the training cohort, and 22 endometriosis-related IRGs were identified by overlapping the 1,116 DEGs, 3,222 module genes, and 1,793 IRGs. Meanwhile, 45 endometriosis-related ARGs were obtained (1,928 ARGs). Subsequently, nine IRG hub genes (BST2, CCL13, CD86, CSF1, FAM3C, GREM1, ISG20, PSMB8, and S100A11) and nine ARG hub genes (GSK3A, HTR2B, RAB3GAP1, ARFIP2, BNIP3, CSF1, MAOA, PPP1R13L, and SH3GLB2) were obtained by LASSO and SVM-RFE. GO analysis indicated that the ARG hub genes responded to the regulation of autophagy and mitochondrial outer membrane permeabilization, and KEGG enrichment analysis involved serotonergic and dopaminergic synapses. GO analysis also indicated that the IRG hub genes responded to the regulation of leukocyte proliferation and mononuclear cell migration, and KEGG analysis showed enrichment involved in viral protein interaction with cytokines and cytokine receptors. The AUC of the random-forest algorithm of ARGs was 0.975 in the training cohort and 0.940 in the validation cohort, and the AUC of the SMO algorithm of IRGs was 0.907 in the training cohort and 0.8 in the validation cohort. Conclusions: Seventeen hub genes are closely associated with endometriosis. These genes are potential autophagy- and immune-related biomarkers for diagnosis and treatment of endometriosis.

[Mechanism of Shaofu Zhuyu Decoction in treatment of EMT induced dysmenorrhea based on network pharmacology and molecular docking].

Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) were searched for the effective components and targets of Shaofu Zhuyu Decoction. The relevant targets for endometriosis(EMT) and dysmenorrhea were retrieved from the Comparative Toxicogenomics Database(CTD), Therapeutic Target Database(TTD), GeneCards, and DisGeNET with the terms of "endometriosis" and "dysmenorrhea". Cytoscape 3.8.0 was employed to construct the drug-active component-therapeutic target network. A protein-protein interaction(PPI) network was established by STRING 11.0. Analyze Network, the plug-in in the Cytoscape 3.8.0, was used to calculate the topological parameters of the nodes and screen out the critical proteins in the network. The potential therapeutic targets were imported into RStudio and subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses with clusterProfiler package. Finally, the AutoDock Vina(Vina) platform was used for molecular docking to predict the binding degree of the main active components of Shaofu Zhuyu Decoction to key targets. As revealed by the screening results, 136 active components and 380 targets of Shaofu Zhuyu Decoction were obtained. Additionally, there were 1 627 targets related to EMT and 142 targets related to dysmenorrhea with 107 common targets, and 42 potential therapeutic targets of Shaofu Zhuyu Decoction for the treatment of EMT-induced dysmenorrhea. The targets such as interleukin 6(IL6) and prostaglandi-nendoperoxide synthase-2(PTGS2) were pivotal in the biological network of Shaofu Zhuyu Decoction intervention in EMT-induced dysmenorrhea, which involved multiple signaling pathways, including inflammation, hormones, and those promoted cell proliferation [e.g., mitogen-activated protein kinase(MAPK) and phosphatidylinositol-3 kinase(PI3 K)-protein kinase B(AKT)]. The results of molecular docking showed that the active components of Shaofu Zhuyu Decoction had good binding capacities to key targets such as IL6 and PTGS2. The findings of this study demonstrated that Shaofu Zhuyu Decoction could treat EMT-induced dysmenorrhea through multiple targets and multiple pathways, which could provide new ideas for investigating the underlying mechanism of Shaofu Zhuyu Decoction in the treatment of EMT-induced dysmenorrhea.

Association between an indel polymorphism within the distal promoter of EGLN2 and cancer risk: An updated meta-analysis.

BACKGROUND: The association between a 4-bp indel polymorphism (rs10680577) within the distal promoter of EGLN2 and cancer risk has been investigated by several case-control studies in recent years, but investigation results were inconsistent. Thus, a systematic assessment of the association was performed based on a literature review and pooled analysis. METHODS: Two investigators independently retrieved relevant studies from PubMed, Chinese National Knowledge Infrastructure (CNKI), Embase, and Google Scholar. The fixed or random effects model was selected to calculate odds ratios (ORs) with 95% confidence intervals (CIs) based on heterogeneity level. All analyses including heterogeneity assessment, subgroup analysis, sensitivity analysis, and publication bias assessment were performed using RevMan 5.3 software and Stata 12.0 software. RESULTS: A total of six relevant studies with 3,406 cases and 5,147 controls were included in the final analysis. The overall pooled analysis showed that EGLN2 rs10680577 polymorphism was significantly associated with cancer risk under all genetic models. However, subgroup analysis based on cancer type showed that the polymorphism was significantly associated with the risk of digestive system cancer under all genetic models, and with the risk of lung cancer under dominant model, heterozygote comparison model, and allele comparison model. Subgroup analysis based on population sources showed a significant association in Chinese population under all genetic models. CONCLUSION: The present result suggests that EGLN2 rs10680577 polymorphism is associated with cancer risk, and may act as a promising predictive biomarker for cancer risk, especially in Chinese population. However, further well-designed studies are warranted to confirm these results.