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Abstract The ideal tissue engineering scaffold should facilitate rapid cell infiltration and provide an optimal immune microenvironment during interactions with the host. Electrospinning can produce two-dimensional (2D) membranes mimicking the extracellular matrix. However, their dense structure hinders cell penetration, and their thin form restricts scaffold utility. In this study, latticed hydrogels were three-dimensional (3D) printed onto electrospun membranes. This technique allowed for layer-by-layer assembly of the membranes into 3D scaffolds, which maintained their resilience impressively under both dry and wet conditions. We assessed the cellular and host responses of these 3D nanofiber scaffolds by comparing random membranes and mesh-like membranes with three different mesh sizes (250, 500, and 750 μm). It was found that scaffolds with a mesh size of 500 μm were superior for M2 macrophage phenotype polarization, vascularization, and matrix deposition. Furthermore, it was confirmed by subsequent experiments such as RNA sequencing that the mesh-like topology may promote polarization to the M2 phenotype by affecting the PI3K/AKT pathway. In conclusion, our work offers a novel method for transforming 2D nanofiber membranes into 3D scaffolds. This method boasts flexibility, allowing for the use of varied electrospun membranes and hydrogels in terms of structure and composition. It has vast potential in tissue repair and regeneration.

Abstract Metabolic disorder has been found to be an important factor in the pathogenesis and progression of sepsis. However, the causation of such an association between serum metabolites and sepsis has not been established. We conducted a two-sample Mendelian randomization (MR) study. A genome-wide association study of 486 human serum metabolites was used as the exposure, whereas sepsis and sepsis mortality within 28 days were set as the outcomes. In MR analysis, 6 serum metabolites were identified to be associated with an increased risk of sepsis, and 6 serum metabolites were found to be related to a reduced risk of sepsis. Furthermore, there were 9 metabolites positively associated with sepsis-related mortality, and 8 metabolites were negatively correlated with sepsis mortality. In addition, “glycolysis/gluconeogenesis” (p = 0.001), and “pyruvate metabolism” (p = 0.042) two metabolic pathways were associated with the incidence of sepsis. This MR study suggested that serum metabolites played significant roles in the pathogenesis of sepsis, which may provide helpful biomarkers for early disease diagnosis, therapeutic interventions, and prognostic assessments for sepsis.

Cytokin storms play a key role in the pathogenesis of acute lung injury (ALI) caused by sepsis, in which pulmonary macrophage PANoptosis is involved. At present, the main treatment methods for sepsis-induced ALI are antibiotics and fluid resuscitation, but the efficacy of these methods is unsatisfactory enough; therefore, the development of new therapeutic methods is urgently needed. In this study, we developed a novel bionic nanoparticle (R@ZQC NPs) using ZIF-8 nanoparticles as a carrier, internally supported with ginsenoside Rb1, and externally coated with quaternated chitosan and a macrophage membrane layer by layer. The biomimetic nanoparticles controlled the release of Rb1, had good biocompatibility, strong antibacterial activity, and targeted the inhibition of pulmonary macrophage PANoptosis. In vitro and in vivo, R@ZQC NPs effectively inhibited the activity of Escherichia coli and reduced mitochondrial damage by activating the AMPK pathway, thus alleviating the inflammatory response and ameliorating sepsis-induced ALI. In summary, this study revealed the great potential of R@ZQC NPs for antimicrobial activity, targeted inhibition of macrophage PANoptosis and reduction of the inflammatory response and represents the first attempt of R@ZQC NPs in the treatment of sepsis-induced ALI. This study provides new therapeutic ideas and strategies for the clinical treatment of sepsis-induced ALI.

Abstract The treatment of bone defects remains a substantial clinical challenge due to the lack of spatiotemporal management of the immune microenvironment, revascularization, and osteogenic differentiation. Herein, deferoxamine (DFO)‐loaded black phosphorus nanosheets decorated by polydopamine layer are prepared (BPPD) and compounded into gelatin methacrylate/sodium alginate methacrylate (GA) hybrid hydrogel as a smart‐responsive therapeutic system (GA/BPPD) for accelerated bone regeneration. The BPPD nanocomposites served as bioactive components and near‐infrared (NIR) photothermal agents, which conferred the hydrogel with excellent NIR/pH dual‐responsive properties, realizing the stimuli‐responsive release of DFO and PO43 − during bone regeneration. Under the action of NIR‐triggered mild photothermal therapy, the GA/BPPD hydrogel exhibited a positive effect on promoting osteogenesis and angiogenesis, eliminating excessive reactive oxygen species, and inducing macrophage polarization to the M2 phenotype. More significantly, through macrophage M2 polarization‐induced osteoimmune microenvironment, this hydrogel platform could also drive functional cytokine secretion for enhanced angiogenesis and osteogenesis. In vivo experiments further demonstrated that the GA/BPPD system could facilitate bone healing by attenuating the local inflammatory response, increasing the secretion of pro‐healing factors, stimulating endogenous cell recruitment, and accelerating revascularization. Collectively, the proposed intelligent photothermal hydrogel platform provides a promising strategy to reshape the damaged tissue microenvironment for augmented bone regeneration.

Abstract Background Polyunsaturated fatty acid (PUFA) synthase is a multi-domain mega-enzyme that effectively synthesizes a series of PUFAs in marine microorganisms. The dehydratase (DH) domain of a PUFA synthase plays a crucial role in double bond positioning in fatty acids. Sequencing results of the coccolithophore Emiliania huxleyi (E. huxleyi, Eh) indicated that this species contains a PUFA synthase with multiple DH domains. Therefore, the current study, sought to define the functions of these DH domains (EhDHs), by cloning and overexpressing the genes encoding FabA-like EhDHs in Escherichia coli (E. coli) and Arabidopsis thaliana (A. thaliana). Results A complementation test showed that the two FabA-like DH domains could restore DH function in a temperature-sensitive (Ts) mutant. Meanwhile, overexpression of FabA-like EhDH1 and EhDH2 domains increased the production of unsaturated fatty acids (UFAs) in recombinant E. coli by 43.5–32.9%, respectively. Site-directed mutagenesis analysis confirmed the authenticity of active-site residues in these domains. Moreover, the expression of tandem EhDH1-DH2 in A. thaliana altered the fatty acids content, seed weight, and germination rate. Conclusions The two FabA-like DH domains in the E. huxleyi PUFA synthase function as 3-hydroxyacyl-acyl carrier protein dehydratase in E. coli. The expression of these domains in E. coli and A. thaliana can alter the fatty acid profile in E. coli and increase the seed lipid content and germination rate in A. thaliana. Hence, introduction of DH domains controlling the dehydration process of fatty acid biosynthesis in plants might offer a new strategy to increase oil production in oilseed plants.

We investigated the optimum co-culture ratio with the highest biological nitrogen removal rate, revealing that chemical oxygen demand, total nitrogen (TN), and ammoniacal nitrogen (NH3-N) removal was increased in the Chlorella pyrenoidosa and Yarrowia lipolytica co-culture system at a 3:1 ratio. Compared with the control, TN and NH3-N content in the co-incubated system was decreased within 2–6 days. We investigated mRNA/microRNA (miRNA) expression in the C. pyrenoidosa and Y. lipolytica co-culture after 3 and 5 days, identifying 9885 and 3976 differentially expressed genes (DEGs), respectively. Sixty-five DEGs were associated with Y. lipolytica nitrogen, amino acid, photosynthetic, and carbon metabolism after 3 days. Eleven differentially expressed miRNAs were discovered after 3 days, of which two were differentially expressed and their target mRNA expressions negatively correlated with each other. One of these miRNAs regulates gene expression of cysteine dioxygenase, hypothetical protein, and histone-lysine N-methyltransferase SETD1, thereby reducing amino acid metabolic capacity; the other miRNA may promote upregulation of genes encoding the ATP-binding cassette, subfamily C (CFTR/MRP), member 10 (ABCC10), thereby promoting nitrogen and carbon transport in C. pyrenoidosa. These miRNAs may further contribute to the activation of target mRNAs. miRNA/mRNA expression profiles confirmed the synergistic effects of a co-culture system on pollutant disposal.

The reconstruction of large bone defects by bioactive materials without exogenous cells, cytokines or growth factors remains a substantial clinical challenge. Herein, we present the rational design of injectable and adhesive (GMAD/LP) hydrogels composed of gelatin-methacryloyl (GelMA), dopamine-grafted alginate (AD), and polydopamine-functionalized Laponite (Lap@PDA) nanosheets that can act as osteoimmune regulators to engineer the pro-regenerative microenvironment for personalized bone regeneration. The as-fabricated GMAD/LP hydrogel with excellent tissue adhesion, self-healing, injectability, and improved mechanical strength can fill irregular bone defects in a minimally invasive manner. Moreover, the hydrogel exhibited outstanding osteogenic potential and osteoimmunomodulatory functions in vitro, significantly promoting the adhesion, proliferation, spreading, and osteogenic differentiation of bone mesenchymal stem cells (BMSCs), which was further augmented by hydrogel-induced macrophage M2-phenotype polarization and effective M2 macrophage-BMSC crosstalk. In vivo experiments in a cranial defect model demonstrated that the GMAD/LP hydrogel induced a reparative microenvironment similar to that in normal cranium, as characterized by an increased percentage of anti-inflammatory M2 macrophages and endogenous stem cells and high-level neovascularization, consequently accelerating bone healing. This strategy not only achieves a bioactive hydrogel for bone defect reconstruction but also provides a feasible methodology to recover injured bone tissue through integrated design with diverse functions.

IntroductionPomelo is one of the most consumed fruits due to its distinct flavor and sour taste, while large quantities of pomelo fruitlets discard during cultivation and most of them are disposed of as wastes. Such an issue has led to some research on how to make a high value-added reutilization of these fruitlets. Therefore, it was aimed to determine the structural characteristics of the polysaccharide of pomelo fruitlets and evaluate its attenuating effect on the hepatic lipid accumulation in hybrid groupers (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀).Methods and resultsIn this research, YZ-0.5A is a 15,332 Da NaCl-soluble polysaccharide extracted from pomelo fruitlet which was characterized to mainly contain galactose and galacturonic acid and its putative structure was proven to be →2,4)- α-L-Rhap-(1→4)-α-D-GalAp-(1→4)-α-D-GalAp-(1→ with 3 branches. In vivo study, five isolipidic diets (containing 15% lipid) were fed to the groupers with an initial weight of 13.46 ± 0.08 g for 8 weeks, of which the dietary level of YZ-0.5A was 0 mg/kg (control), 150 mg/kg, 300 mg/kg, 600 mg/kg and 1200 mg/kg respectively. We found that the treatment of YZ-0.5A, especially 600 mg/kg, exerted an improved effect on the excessive lipid accumulation in grouper fed with a high-fat diet. In vitro, three graded concentrations of YZ-0.5A (75, 150 or 300 μg/ml) were added to the grouper primary hepatocytes respectively after incubation with 20% lipid emulsion (2 ml/L). The signs of recovery on morphological features observed under examined by histological evaluation supported the lipid lowering effect of YZ0.5-A. Further investigation showed that YZ0.5-A mitigated lipid emulsion-induced irregular lipid deposition by regulating various lipometabolism-related indicators, thereby alleviating oxidative stress and apoptosis. DiscussionOverall results exhibited the therapeutic potential of YZ0.5-A and elucidated its underlying mechanism in the fish with excessive lipid deposition, which first suggested the feasibility of reprocessing discarded pomelo fruitlet as medicine in aquaculture.

To predict the maturity of bananas, the present study used non-destructive methods to analyze changes in the sweetness and color of the stalks, middles, and tips of bananas during ripening. The results indicated that the respective maturation of these three segments did not occur simultaneously, as indicated by the differential enzyme activity and gene expression levels recorded in these segments. A principal component analysis and cluster plots were used to review the classification of banana maturity, highlighting that banana maturation can be divided into six stages. Two distinct maturity prediction algorithms were established using random forest, artificial neural network, and support vector machines, and they also indicated that dividing the maturity of bananas into six stages was adequate. These findings contribute to the development of quality evaluation and of a rapid grading system for processing, which improves the quality and sale of banana fruits and the related processed products.

Recently, strategies that focus on biofunctionalized implant surfaces to enhance bone defect healing through the synergistic regulation of osteogenesis, angiogenesis, and osteoclastogenesis have attracted increasing attention in the bone tissue engineering field. Studies have shown that the Wnt/β-catenin signaling pathway has an imperative effect of promoting osteogenesis and angiogenesis while reducing osteoclastogenesis. However, how to prepare biofunctionalized bone implants with balanced osteogenesis, angiogenesis, and osteoclastogenesis by activating the Wnt/β-catenin pathway has seldom been investigated. Herein, through a bioinspired dopamine chemistry and self-assembly method, BML-284 (BML), a potent and highly selective Wnt signaling activator, was loaded on a mussel-inspired polydopamine (PDA) layer that had been immobilized on the porous beta-tricalcium calcium phosphate (β-TCP) scaffold surface and subsequently modified by a biocompatible carboxymethyl chitosan hydrogel to form a sandwich-like hybrid surface. β-TCP provides a biomimetic three-dimensional porous microenvironment similar to that of natural cancellous bone, and the BML-loaded sandwich-like hybrid surface endows the scaffold with multifunctional properties for potential application in bone regeneration. The results show that the sustained release of BML from the sandwich-like hybrid surface significantly facilitates the adhesion, migration, proliferation, spreading, and osteogenic differentiation of MC3T3-E1 cells as well as the angiogenic activity of human umbilical vein endothelial cells. In addition to osteogenesis and angiogenesis, the hybrid surface also exerts critical roles in suppressing osteoclastic activity. Remarkably, in a critical-sized cranial defect model, the biofunctionalized β-TCP scaffold could potentially trigger a chain of biological events: stimulating the polarization of M2 macrophages, recruiting endogenous stem cells and endothelial cells at the injury site to enable a favorable microenvironment for greatly accelerating bone ingrowth and angiogenesis while compromising osteoclastogenesis, thereby promoting bone healing. Therefore, these surface-biofunctionalized β-TCP implants, which regulate the synergies of osteogenesis, angiogenesis, and anti-osteoclastogenesis, indicate strong potential for clinical application as advanced orthopedic implants.

Bergamot (Citrus medica L. var. sarcodactylis) contains different bioactive compounds, and their effects remain unclear. Therefore, the structural and bio-function of bergamot dietary fiber were investigated. A sequential extraction procedure was utilized to obtain soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) from bergamot. The main monosaccharide in SDF and IDF is arabinose. SDF had a porous structure, which enhanced the water and oil holding capacity, as well as the cholesterol and glucose adsorption capacity, which was superior to that of IDF. In db/db diabetic mice, SDF and IDF regulated glucose tolerance and controlled blood glucose levels. Reduction of serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol in SDF and IDF could be observed. In summary, SDF and IDF from bergamot effectively promoted health in patients with diabetes.

Abstract Background The top of the olecranon honey peach (Prunus persica L.) fruit appears similar to an eagle’s beak. In this study, a single olecranon honey peach with a round-type fruit was observed in our fruit orchard. To explore the genetic mechanism of olecranon formation, we performed full-length transcriptome sequencing analysis of olecranon and round peaches as well as a genome-wide association study of the association of olecranon-type trait loci. Results The gene locus was 26,924,482 base pairs in NC_034014.1. Transcriptome sequencing showed that the clean sequencing data of each sample reached 7.10GB, with 14,360 genes and 23,167 transcripts expressed in both the olecranon honey peach and round peach. Among the 11 differentially expressed genes selected as candidate genes, six were highly expressed in olecranon peach and named as LOC18775282, LOC18772209, LOC18773929, LOC18772013, LOC18773401, and ONT.13798.5. Five genes were highly expressed in round peach and named as LOC18773079, LOC18773525, LOC18773067, LOC18775244, and LOC18772236. Notably, ONT.13798.5 was not previously identified. The genes were within 1 Mb up- or down-stream of the main genome-wide association study locus for olecranon-type traits. Conclusions This study revealed loci associated with olecranon and provides useful information for analysis and breeding of olecranon honey peach.

Bioinspired materials with dual capabilities of pro-osteogenesis and pro-angiogenesis have attracted increasing scientific interest in the field of orthopedics. Herein, inspired by the mineralization process of natural bone, a biomimetic strategy is presented to fabricate highly bioactive hybrid nanocomposite scaffolds via impregnation of Si-containing polymer-induced liquid precursor (PILP) into biocompatible porous gelatin scaffolds followed by in situ free radial polymerization. The well-designed biohybrid scaffold exhibited not only a micro/nano fiber-like porous architecture (pore size: 100–200 μm; porosity: 80–90 %), high specific surface area (≈20 m2/g), vastly improved mechanical performance, tunable swelling and degradation behaviors but also a sustained release profile of bioactive Si ions up to 21 days. In vitro experiments revealed the excellent biological performance of the resulting biohybrid scaffold, including good biomineralization capacity and biocompatibility, establishing a favorable microenvironment for facilitating cell adhesion, proliferation, migration, osteogenic differentiation, and vascularization. In rat calvarial critical-size defect models, the newly developed biohybrid scaffold could potentially trigger a chain of biological events: stimulating the polarization of M2 macrophages, recruiting endogenous stem cells and endothelial cells at the injury site to enable a suitable regenerative microenvironment for accelerating coupled osteogenesis and angiogenesis, and eventually promoting vascularized bone regeneration.

Previously, we found that ASP-ASP-ASP-TYR (DDDY) from Dendrobium aphyllum has a minimum inhibitory concentration of 36.15 mg/mL against Pseudomonas aeruginosa. Here, we explored the antibacterial mechanism of DDDY and its potential preservation applications. Metabolomic and transcriptomic analyses revealed that DDDY mainly affects genes involved in P. aeruginosa membrane transport and amino acid metabolism pathways. Molecular dynamics simulation revealed that DDDY had a stronger effect on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine phospholipid membranes than on 1-palmitoyl-2-oleoyl-lecithin or 1-palmitoyl-2-oleoyl phosphatidylglycerol membranes, with high DDDY concentrations displaying stronger efficacy on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine. Mechanistically, the N-terminal of DDDY first bound to the phospholipid head group, while its C-terminal amino acid residue bound the hydrophobic tail, thereby creating a gap in the membrane when the phospholipids were clustered by hydrogen bonding. Finally, DDDY inhibited the growth of food microorganisms inoculated onto chestnut kernels, suggesting that DDDY is a promising antibacterial agent against multidrug-resistant gram-negative bacteria.

Chemoresistance remains a huge challenge for the treatment of osteosarcoma (OS). Multiple mechanisms are involved in chemoresistance of cisplatin. In our research, we found that Nrf2/xCT pathway contributes to the occurrence of chemoresistance of cisplatin in OS by enhancing the ability of antioxidative stress. Recently, oxidative stress defense and ferroptosis have attracted wildly attention in overcoming chemoresistance. Different from apoptosis, necroptosis, and autophagy, ferroptosis is a new programmed cell death pathway with the accumulation of reactive oxygen species (ROS). Synergistic treatment of ferroptosis and photothermal therapy (PTT) can perfectly overcome chemoresistance, and immunogenic cell death (ICD) induced by PTT can initiate effective anti-tumor immunity to suppress tumor growth and recurrence. Thus, we designed a cancer cell membrane coated gold nanocages loaded with RSL3 (C-R-AuNC) for the treatment of chemoresistance of OS. RSL3 induces ferroptotic cell death by the inhibition of glutathione peroxidase (GPX4). Gold nanocages coated with the cell membrane, as a nanocarrier, can achieve targeted drug delivery, controlled drug release, PTT, and induced ICD. In our researches, excellent outcomes for the treatment of chemoresistance of OS were achieved by C-R-AuNC, which is believed to serve as a promising strategy for clinic treatment of drug-resistant OS in future.

Plant polysaccharides exert a wide range of biological effects on the intestinal function. In this study, four polysaccharides containing β-D-Glup, including Dendrobium officinale polysaccharide (DOP), Dendrobium aphyllum polysaccharide (DAP), and glucans from yeast (G-Y) and barley (G-B), were investigated in vitro for their intestinal-promoting functions such as inhibition of digestive enzymes, effect of blood glucose and blood lipid levels by using ultraviolet spectrophotometry, as well as the relationship of their structures to those functions. The results indicated that all polysaccharides significantly slowed glucose diffusion rate, decreased protease, and pancreatic lipase activities. Increased branching degrees had a deleterious effect on the α-amylase activity but increased bile acid binding. Increased calcium concentration in glucans (G-Y and G-B) and increased mannose molar ratio in Dendrobium polysaccharides (DOP and DAP) were correlated with increased pancreatic lipase inhibition. The polysaccharides with higher glucose content and branching degrees had higher bile acid binding and disruption of cholesterol micelle formation. These polysaccharides exerted a variety of potential health-promoting effects attributed to their different structures, which should be further investigated in vivo.

We evaluated dendrobine for its potential effect on Inflammatory Bowel Disease (IBD) progression using the intestinal epithelial Caco-2/RAW264.7 macrophage co-culture cell model. The results showed that dendrobine maintained the tight junction (TJ) proteins in co-cultured Caco-2 cells, suggesting its protective effect on intestinal integrity. Moreover, the findings indicated that the dendrobine group downregulated levels of tumor necrosis factor-α (TNF-α), proinflammatory Interleukin (IL)-1β and IL-6, and inflammatory markers such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in co-cultured RAW264.7 cells. Additionally, dendrobine-mediated anti-inflammatory effects were observed based on the inhibition of LPS-induced proinflammatory mediators of nuclear factor kappa B (NF-κB)-related signaling. These results demonstrated the protective effect of dendrobine at effectively ameliorating intestinal barrier disruption and inhibiting activation of the NF-κB pathway in macrophages through the intestinal barrier.

In this study, the antioxidant components in co-culture of Chlorella pyrenoidosa and Yarrowia lipolytica (3:1 ratio) were confirmed as trypsin-hydrolyzed peptides (EHPs). The EHPs were composed of 836 different peptides with molecular weights ranging from 639 to 3531 Da and were mainly composed of hydrophobic amino acids (48.1%). These peptides showed remarkable protective effects against oxidative stress in HepG2, which may be attributed to their structures. Furthermore, the mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) were significantly lower in the peptide-treated group than in the control group, suggesting that the antioxidant enzyme-coding genes were not activated. The EC50 value of three peptides in the EHPs were in the order of AGYSPIGFVR (0.04 ± 0.002 mg/mL) > VLDELTLAR (0.09 ± 0.001 mg/mL) > LFDPVYLFDQG (0.41 ± 0.03 mg/mL); these results agreed with the prediction of the model (R2 > 0.9, Q2 > 0.5). Thus, EHPs show potential as potent new antioxidant agents.

Aquatic foods are nutritious, enjoyable, and highly favored by consumers. In recent years, young consumers have shown a preference for prefabricated food due to its convenience, nutritional value, safety, and increasing market share. However, aquatic foods are prone to microbial spoilage due to their high moisture content, protein content, and unsaturated fatty acids. Furthermore, traditional processing methods of aquatic foods can lead to issues such as protein denaturation, lipid peroxidation, and other food safety and nutritional health problems. Therefore, there is a growing interest in exploring new technologies that can achieve a balance between antimicrobial efficiency and food quality. This review examines the mechanisms of cold plasma, high-pressure processing, photodynamic inactivation, pulsed electric field treatment, and ultraviolet irradiation. It also summarizes the research progress in nonthermal physical field technologies and their application combined with other technologies in prefabricated aquatic food. Additionally, the review discusses the current trends and developments in the field of prefabricated aquatic foods. The aim of this paper is to provide a theoretical basis for the development of new technologies and their implementation in the industrial production of prefabricated aquatic food. [ABSTRACT FROM AUTHOR]

Several macromolecules from the pomelo fruitlet (PF) have demonstrated functional potential in previous research. In this study, pomelo fruitlet albumin (PFA) was extracted from PF, its anti-inflammatory and anti oxidant properties were assessed using enzyme-linked immunosorbent assays, and its capacity to clear free radicals was measured. Meanwhile, we hypothesize that the amino acid sequence may affect the anti- inflammatory and antioxidant properties, and the two may rely on common significant sites within the amino acid sequence. Therefore, we analyzed the amino acid sequence using a quantitative structure–activity relationship model to explore the connection between the antioxidant and anti-inflammatory capacities of PFA. Both capacities were closely associated with six sites within the amino acid sequence. Collectively, this study illustrates that PFA exhibits both anti-inflammatory and antioxidant capacities, with six specific sites identified as significantly affecting both activities. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The role of miR-365 in cancer cells seemed controversial in previous studies. We thereby in this article aimed to define the role of miR-365 in malignant melanoma (MM) pathogenesis. METHODS:We detected miR-365 expression in malignant melanoma cell lines and then investigated the effects of miR-365 on the metastasis and malignancy of melanoma cells. The correlation between miR-365 level and NRP1 (neuropilin1) was further investigated in clinical malignant melanoma specimens. RESULTS: MiR-365 was strongly down-regulated in malignant melanoma (MM) tissues and cell lines, and its expression levels were associated with lymph node metastasis and clinical stage, as well as overall survival and replase-free survival of MM. We also found that ectopic expression of miR-365 inhibited MM cell proliferation and MM metastasis in vitro and in vivo. We further identified a novel mechanism of miR-365 to suppress MM growth and metastasis. NRP1 was proved to be a direct target of miR-365, using luciferase assay and western blot. NRP1 over-expression in miR-365 expressing cells could rescue invasion and growth defects of miR-365. In addition, miR-365 expression inversely correlated with NRP1 protein levels in MM. CONCLUSION: Our data suggest that miR-365 functions as a tumor suppressor in MM development and progression, and holds promise as a prognostic biomarker and potential therapeutic target for MM. [ABSTRACT FROM AUTHOR]