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Fast skin repair is critical for less infection, less pain and high quality of life, which is still limited with undesirable rehabilitation speed and side effects. Currently, laser-activated silk sealant agent without suture and gauze has been demonstrated promising for fast skin repair taking advantage of its structural transformation after heating. Nevertheless, more efficient healing effects and less side effects of laser-activated silk sealant agent remains challenging due to absence of suitable photo-thermal materials and robust/biomimetic protein materials. In this work, the marriage between silk protein and Rehmanniae radix preparata (a kind of the traditional Chinese herb) has been demonstrated as a novel and effective way to achieve an excellent healing effect for skin repair. The non-toxicity, high photothermal conversion efficiency and healing mechanism are systematically studied and proved. This new methodology might shed a new light for combining dark traditional Chinese medicine and silk fibroin for advanced wound healing technology.

Nobiletin was found to mitigate nonalcoholic fatty liver disease by enhancing TFEB-mediated lipophagy, alleviating NLRP3 inflammasome and modulating macrophages polarization.

To date, various Prussian blue analogues (PBAs) have been prepared for biomedical applications due to their unique structural advantages. However, the safety and effectiveness of tumor treatment still need further exploration. This contribution reports a facile synthesis of PBA with superior tumor synergetic therapeutic effects and a detailed mechanistic evaluation of their intrinsic tumor metastasis inhibition activity. The as-synthesized PBA has a uniform cube structure with a diameter of approximately 220 nm and shows high near-infrared light (NIR) photoreactivity, photothermal conversion efficiency (41.44%), and photodynamic effect. Additionally, PBA could lead to a chemodynamic effect, which is caused by the Fenton reaction and ferroptosis. The combined therapy strategy of PBA exhibits notable tumor ablation properties due to photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT) effects without obvious toxicity

Nonalcoholic fatty liver disease (NAFLD), an increasingly serious health issue around the world, is characterized as a lipid metabolic disorder without any satisfactory treatment. Nobiletin (NOB), a citrus flavonoid, is considered a promising candidate for NAFLD prevention although there is limited research towards its exact mechanism. In this study, the preventative effect of NOB on NAFLD was investigated using high fat diet-fed ApoE

Breast cancer is the most common malignancy in women all around the world, especially in many countries in Asia. However, antitumor drugs with unique curative effects and low toxic side-effects have not been found yet. Warangalone is an isoflavone extracted from the Cudrania tricuspidata fruit, and is reported to possess anti-inflammatory and anti-cancer activity. The purpose of this study was to determine the effects of warangalone on breast cancer cells. In this study, we found that warangalone decreased the viability of breast cancer cells by increasing the generation of reactive oxygen species (ROS) resulting in mitochondrial damage and decreased mitochondrial membrane potential (MMP). Warangalone induced mitochondrial apoptosis by increasing the BAX/BCL-2 ratio. Warangalone activated mitophagy via upregulation of PINK1 and Parkin expression and co-localization. The combination of warangalone and autophagy inhibitors or PINK1 siRNA increased the degree of cell apoptosis compared to treatment with warangalone alone. Warangalone damages mitochondria via ROS, thereby triggering PINK1/Parkin-mediated mitophagy and inducing mitochondrial apoptosis. However, autophagy/mitophagy protects against warangalone-induced mitochondrial apoptosis. A combination of warangalone and autophagy/mitophagy inhibitors may be a potential treatment for breast cancer.

Cardiovascular diseases (CVDs) have been ranked as the leading cause of death in the world, whose global incidence is increasing year by year. Citrus, one of the most popular fruits in the world, is rich in flavonoids. Citrus flavonoids attract special attention due to a variety of biological activities, especially in the prevention and treatment of CVDs. The research progress of citrus flavonoids on CVDs have been constantly updated, but relatively fragmented, which needed to be systematically summarized. Hence, the recent research about citrus flavonoids and CVDs were reviewed, including the types and in vivo processes of citrus flavonoids, epidemiology study and mechanism on prevention and treatment of CVDs by citrus flavonoids. This review would provide a theoretical basis for the citrus flavonoids research and a new idea in the citrus industry development and application.

The aim of this study is to investigate whether Flammuliana Velutipes Polysaccharide (FVP) could aid in the prevention of colitis. Effect of FVP on colitis was evaluated using dextran sulfate sodium (DSS)-induced colitis in rats. Influence of FVP on the expression of inflammation related biomarkers and signal pathway element of TLR4\NF-κB were assessed. The composition and taxonomy of colonic microbiota were analyzed by 16S rDNA high throughput sequencing, and the concentrations of caecal short fatty chain acids were assessed by chromatography-mass spectrometry. Our results showed that FVP treatment could regulate the colonic microbial dysbiosis and promote the levels of caecal short fatty chain acids, leading to down-regulation of TLR4\NF-κB signal pathway, which finally ameliorate the colitis. Thus, the present study is the first attempt to elucidate the effect of FVP on colitis and support the potential application of FVP as a functional food ingredient or preventive drugs for colitis.

The composite hydrogel was prepared with cellulose and flaxseed gum and characterized by fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Brunauer–Emmitt–Teller (BET) and thermogravimetric analysis (TGA). The swelling property, drug adsorption, biocompatibility and hemostatic function of composite hydrogel were investigated. The composite hydrogel had the pore structure and exhibited high stability with a thermal decomposition temperature of 332.66 °C. And the composite hydrogel showed excellent swelling capability with a moisture expansivity of over 200%, and with a drug adsorption capacity of 7.27 ± 0.15 mg/g. Mechanical properties tests showed that as the proportion of flaxseed gum increased, the ability to withstand pressure of hydrogel was improved. In addition, MTT assay, flow cytometry analysis, and in vivo toxicological evaluation suggested that composite hydrogel had good biocompatibility. Moreover, hemostatic potential assay and wound healing were made in order to evaluate the effect of hemostasis and wound healing of composite hydrogel and our results indicated that the composite hydrogel with cellulose and flaxseed gum could be effective to promote hemostatic and wound healing function. All in all, the great properties exhibited by the composite hydrogel could make it a potential candidate as biomaterial in bleeding and wound treatment.

The structural characteristics of a novel Flammulina velutipes polysaccharide (FVP2) were explored in this study. Besides, immunomodulatory activities of FVP2 on RAW 264.7 cell and its impact on gut microbiota in rats were investigated. FVP2 has a molecular weight of 18.3 kD, and its main components include galactose (19.96%), glucose (60.66%) and mannose (19.38%). By NMR analysis, the main-chain structure consisted of (1 → 3)-linked-β-D-Gal, (1 → 6) -linked-β-D-Gal, (1 → 6)-linked-α-D-Glc and (1 → 3,6)-linked-α-D-Man was identified. Results of the in vitro assays on RAW 264.7 murine macrophage cells showed FVP2 could significantly up-regulate the expression of NO, TNF-α and IL-6. FVP2 was intragastrically administered to rats for 2 weeks. Compared with the control group, two caecal short-chain fatty acids (SCFAs) concentration (isobutyric acid and butyric acid) and the abundance of beneficial microbiota of the FVP2-treated group were significantly increased (p < .05) respectively. The results demonstrated that FVP2 could effectively enhance the level of butyric acid and increase beneficial gut microbiota, which could improve the intestinal barrier function and maintain the intestinal mucosal integrity, suggesting that FVP2 could potentially be an immunomodulators or a functional food to promote intestinal health.

Sodium butyrate (NaB) is a by-product of dietary fiber that has an anti-tumor effect on colorectal cancer (CRC). The aim of this study was to explore the effect of NaB on tumor and colitis using a colitis-associated colorectal cancer (CAC) model. CAC model was induced in mice by administration of azoxymethane (AOM) and dextran sulfate sodium salt (DSS). 0.1 M NaB in drinking water, or intraperitoneal injection of NaB (1 g/kg body weight) was given during the study period. NLRP3 inflammasome-related molecules were detected. The composition and taxonomy of colorectal microbiota were analyzed. NaB increased spleen index decreased by AOM/DSS. NaB attenuated tumors by reducing tumor load and tumor size in AOM/DSS-induced mice. NaB protected mice from CAC by improving colitis and inhibiting expression of NLRP3 and IL-1β. NaB regulated gut microbiota dysbiosis induced by AOM/DSS. In conclusion, NaB inhibited CAC by ameliorating the gut microbiota dysbiosis and inhibiting colitis.

A series of 2-Aryl-4-Bis-amide Imidazoles (ABAI-1 to 30) were designed as anti-inflammatory agents. These compounds were synthesized and evaluated for the in vitro anti-inflammatory activities (inhibition of NO production and release of inflammatory cytokines). Several compounds effectively inhibited NO production in lipopolysaccharide (LPS) induced RAW264.7 cells. Among them, ABAI-30 exhibited the highest NO-inhibitory effect (inhibition rate of 87% at 20 μM). The anti-inflammatory mechanism of ABAI-30 was examined and found to be inhibiting the TLR4-pp65 and NLRP3-caspase-1 signaling pathway, thus leading to the downregulation of IL6, IL-1β and TNFα at both transcriptional and translational levels. Importantly, ABAI-30 demonstrated high in vivo anti-inflammatory efficacy in a dextran sulfate sodium (DSS)-induced colitis mouse model without causing obvious toxicity. Collectively, our study provides a potent anti-inflammatory agent, which deserves further investigation as a novel therapeutic candidate for treating inflammatory bowel diseases.

Multidrug resistance (MDR), defined as the cross-resistance of cancer cells toward a broad range of chemotherapeutic agents, is a universal and intractable problem in chemotherapy. The understanding of MDR mechanisms is essential to discover the potential biomarkers for predicting multidrug resistance and more importantly, tackling and preventing multidrug resistance. Multiple technologies have been used to study MDR mechanisms including comparative genomic hybridization, DNA array, differential display RT-PCR and various immunoassays. Compared with these approaches, proteomic technologies allow a high through-put analysis of protein detection, protein quantification and protein interaction with high accuracy. With the rapid development of proteomic studies in recent years, proteomic technologies have made substantial contributions to the characterization of MDR mechanisms including MDR-related protein detection and quantification, as well as the characterization of drug-transporter binding sites. This review offers a comprehensive illustration of MDR, proteomic technologies and the discoveries made in understanding MDR mechanisms using proteomic approaches.

MicroRNAs are small regulatory noncoding RNAs that regulate various biological processes associated with neurological disorders, cardiovascular diseases, cancer and viral infection. MiRNA-based therapeutics have broad applications including cancer immunotherapy, genomic engineering and protein replacement therapy. Until now, a variety of materials have been proved to be promising as non-viral nanocarriers for intracellular delivery of miRNAs, such as polymeric nanoparticles, lipid nanocapsules, and inorganic nanoparticles, etc. In this review, we will present the strategies for intracellular miRNA delivery, and specially focus on rationally designed routes, their mechanisms of action, and potential therapeutics used in the host cells or in vivo studies. Futhermore, we will also make a conclusion based on the current development. The perspective on the new generation of delivery systems toward the emerging area of miRNA-based therapeutics will be discussed as well.

The effects of a novel Flammulina velutipes polysaccharide (FVP) on intestinal microbiota, immune repertoire and heart transcriptome were investigated in this study. The results showed that FVP treatment could effectively regulate the abundance of colonic microbiota. And FVP exhibited obvious immunoregulatory effect by influencing V gene and J gene fragments usage on TCRα chain. The usage frequency of TRBV1, TRBJ1-6 and TRBJ1-5 were significantly altered, and 41 V-J pairs were identified with obvious difference after FVP treatment. Furthermore, the mRNA of mice heart was analyzed by transcriptome assay. Total 525 genes and 1587 mRNA were significantly changed after FVP treatment. KEGG annotation indicated that the up-regulated mRNA was enriched in 17 pathways including adherens junction, mTOR signaling pathway, insulin signaling pathway, mitophagy, tight junction, PPAR signaling pathway and TNF signaling pathway, etc. Meanwhile, the down-regulated mRNA was gathered in AMPK signaling pathway, metabolism of xenobiotics by cytochrome P450, apelin signaling pathway, PPAR signaling pathway, PI3K-Akt signaling pathway, insulin signaling pathway, cardiac muscle contraction, adrenergic signaling in cardiomyocytes, Fc gamma R-mediated phagocytosis, etc. The great potential exhibited by FVP could make it an ideal candidate as complementary medicine or functional food for promotion of health.

A series of steroidal compounds based on 3-hydroxyandrosta-5,7-diene-17-carboxylic acid core structure were designed, synthesized and bio-evaluated for their anti-inflammatory potency. Among them, compound 5c, 6f, and 6q effectively inhibited the production of nitric oxide (NO) in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophages. They inhibited the expression of inducible NO synthase (iNOS) and prostaglandin synthase-2 (COX-2) at mRNA level. Compound 6q displayed inhibitory effects on both iNOS and COX-2 expression in a concentration-dependent manner. Furthermore, 6q was found to effectively decrease the mRNA and protein levels of interleukin 6 (IL-6). Mechanically, 6q could potently downregulate NF-κB signaling via suppression of the Akt/PI3K pathway. Moreover, 6q demonstrated high in vivo anti-inflammatory activities in a mouse colitis model induced by dextran sulfate sodium (DSS). Taken together, these data indicate that 6q represents a novel and promising anti-inflammatory bowel diseases (IBD) agent worthy of further investigation.

Flammulina velutipes polysaccharides (FVP) can improve gut health through gut microbiota and metabolism regulation. In this study, the 28-days fed experiment was used to investigate gut microbime and metabolic profiling induced by FVP. After treatment, intestinal tissue section showed the higher villus height and villus height/crypt depth (V/C) value in FVP-treated group. The 16 s rRNA gene sequencing revealed microbiota composition alteration caused by FVP, as the Firmicutes phylum increased while Bacteroidetes phylum slightly decreased. The metabolic profiling was detected by LC/MS and results showed 56 and 99 compounds were dramatically changed after FVP treatment in positive and negative ion mode, respectively. Annotation in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways displayed the adjustment of energy metabolism, amino acid metabolism, nucleotide metabolism and other related basic pathways after FVP treatment. Our study suggested that FVP can be developed as a dietary supplement for intestine health promotion.

OBJECTIVE: To prepare warangalone-loaded thermosensitive liposomes (WLTSL) and evaluate its inhibitory effect on breast cancer cells in vitro. METHODS: MTT assay was used to assess the changes in proliferation of 3 breast cancer cell lines (MDA-MB-231, MCF7, and SKBR3) following treatment with warangalone, soy isoflavone and genistein. Colony-forming assay and wound healing assay was used to assess colony forming activity and migration of MDA-MB-231 cells treated with warangalone. The effect of warangalone on the expression of MMP2 and MMP9 in MDA-MB-231 cells was examined with Western blotting. The thermosensitive liposomes (TSL) and WLTSL were prepared using a thin film hydration method, and the morphology, size, encapsulation efficiency and stability of the prepared liposomes were characterized using transmission electron microscopy, dynamic light scattering scanning and UV spectrophotometry. MTT assay was used to examine the inhibitory effect of WLTSL on mouse breast cancer cells (4T1) in vitro. RESULTS: Warangalone showed stronger anti-proliferation effects than soy isoflavones and genistein in the 3 human breast cancer cell lines and significantly inhibited colony formation by MDA-MB-231 cells. Treatment with warangalone significantly inhibited migration of the breast cancer cells and down-regulated the cellular expressions of MMP2 and MMP9. The prepared TSL and WLTSL presented with a homogeneous, irregular spherical morphology, with a mean particle size of 56.23±0.61 nm, a polymer dispersity index of 0.241±0.014, a Zeta potential of -40.40±0.46 mV, and an encapsulation efficiency was 87.68±2.41%. WLTSL showed a good stability at 4 ℃ and 37 ℃ and a stronger inhibitory effect than warangalone in 4T1 cells. CONCLUSION: Warangalone inhibits the proliferation, migration and invasion of breast cancer cells, and the prepared WLTSL possesses good physical properties and strong anti-breast cancer activity.

The biological safety of mesoporous silica nanoparticles (MSNs) has gradually attracted attention. However, few studies of their toxicity to the intestine and mechanism are available. In this study, their primary structures were characterized, and their subacute toxicity to mice was investigated. After 2 weeks of intragastric administration of MSNs, they significantly enhanced serum ALP, ALT, AST and TNF-α levels and caused infiltration of inflammatory cells in the spleen and intestines. MSNs induced intestinal oxidative stress and colonic epithelial cell apoptosis in mice. Intestinal epithelial cells exhibited mitochondrial ridge rupture and membrane potential decrease after MSN treatment. Additionally, MSNs increased ROS and NLRP3 levels and inhibited expression of the autophagy proteins LC3-II and Beclin1. MSNs significantly changed the intestinal flora diversity in mice, especially for harmful bacteria, leading to intestinal microecology imbalance. Meanwhile, MSNs influenced the expression of metabolites, which were involved in a range of metabolic pathways, including pyrimidine metabolism, central carbon metabolism in cancer, protein digestion and absorption, mineral absorption, ABC transport and purine metabolism. These results indicated that the subacute toxicity of mesoporous silicon was mainly caused by intestinal damage. Thus, our research provides additional evidence about the safe dosage of MSNs in the clinical and food industries.

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Hydrogels can be used as bioactive dressings, which outperform traditional dressings and are widely used in wound hemostasis and healing. However, it is still a challenge to develop a hydrogel with good stability and strong mechanical properties for wound hemostasis and healing. Herein, we developed a novel composite polysaccharide hydrogel from fenugreek gum and cellulose. Fenugreek gum was combined with cellulose through hydrogen bonding to form a hydrogel to improve the mechanical properties of the composite hydrogel. The composite hydrogel had a porous structure, thermal stability, good water absorption and a sustained release effect. Furthermore, the composite hydrogel demonstrated good biocompatibility in vitro and in vivo. Notably, the superior performance of wound hemostasis and healing has been confirmed. Our results indicated that the composite hydrogel was a promising medical dressing and had the potential to promote wound healing.

Cardiovascular diseases (CVDs), including a series of pathological disorders, severely affect millions of people all over the world. To address this issue, several potential therapies have been developed for treating CVDs, including injectable hydrogels as a minimally invasive method. However, the utilization of injectable hydrogel is a bit restricted recently owing to some limitations, such as transporting the therapeutic agent more accurately to the target site and prolonging their retention locally. This review focuses on the advances in injectable hydrogels for CVD, detailing the types of injectable hydrogels (natural or synthetic), especially that complexed with stem cells, cytokines, nano-chemical particles, exosomes, genetic material including DNA or RNA, etc. Moreover, we summarized the mainly prominent mechanism, based on which injectable hydrogel present excellent treating effect of cardiovascular repair. All in all, it is hopefully that injectable hydrogel-based nanocomposites would be a potential candidate through cardiac repair in CVDs treatment.

Ovarian cancer is one of the most serious female malignancies worldwide. Despite intensive efforts being made to overcome ovarian cancer, there still remain limited optional treatments for this disease. Nobiletin, a prospective food-derived phytochemical extracted from citrus fruits, has recently been reported to suppress ovarian cancer cells, but the role of pyroptosis in ovarian carcinoma with nobiletin still remains unknown. In this study, we aim to explore the effect of nobiletin on ovarian carcinoma and further expound the underlying mechanisms of nobiletin-induced ovarian cancer cell death. Our results showed that nobiletin could significantly inhibit cell proliferation, induce DNA damage, and also lead to apoptosis by increasing the cleaved poly (ADP-ribose) polymerase (PARP) level of human ovarian cancer cells (HOCCs) in a dose-dependent manner. Moreover, we revealed that nobiletin decreased mitochondrial membrane potential and induced reactive oxygen species (ROS) generation and autophagy of HOCCs, contributing to gasdermin D-/gasdermin E-mediated pyroptosis. Taken together, nobiletin as a functional food ingredient represents a promising new anti-ovarian cancer candidate that could induce apoptosis and trigger ROS-mediated pyroptosis through regulating autophagy in ovarian cancer cells.

Background To date, various Prussian blue analogues (PBA) have been prepared for biomedical applications due to their unique structural advantages. However, the safety and effectiveness of tumor treatment still need further exploration. Results This contribution reports a facile synthesis of novel PBA with superior tumor synergetic therapy effects and a detailed mechanistic evaluation of their intrinsic tumor metastasis inhibition activity. The as-synthesized PBA have a uniform cube structure with a diameter of approximately 220 nm and showed high near infrared light (NIR) photoreactivity, photothermal conversion efficiency (41.44%) and photodynamic effect. Additionally, PBA could lead to chemodynamic effect which caused by Fenton reaction and ferroptosis. The combined therapy strategy of PBA exhibit notable tumor ablation properties due to photothermal therapy (PTT)/photodynamic therapy (PDT)/ chemodynamic therapy (CDT) effect without obvious toxicity in vivo. The PBA also demonstrate potential as a contrast agent for magnetic resonance imaging (MRI) and photoacoustic (PA) imaging. More importantly, careful investigations reveal that PBA displays excellent biodegradation and anti-metastasis properties. Further exploration of this PBA implies that its underlying mechanism of intrinsic tumor metastasis inhibition activity can be attributed to modulation of epithelial mesenchymal transition (EMT) expression. Conclusions The considerable potential exhibits by as-synthesized PBA make it an ideal candidate as a synergetic therapeutic agent for tumor treatment.

Cardiovascular diseases (CVDs) have become a serious threat to human life and health. Though many drugs acting via different mechanism of action are available in the market as conventional formulations for the treatment of CVDs, they are still far from satisfactory due to poor water solubility, low biological efficacy, non-targeting, and drug resistance. Nano-drug delivery systems (NDDSs) provide a new drug delivery method for the treatment of CVDs with the development of nanotechnology, demonstrating great advantages in solving the above problems. Nevertheless, there are some problems about NDDSs need to be addressed, such as cytotoxicity. In this review, the types and targeting strategies of NDDSs were summarized, and the new research progress in the diagnosis and therapy of CVDs in recent years was reviewed. Future prospective for nano-carriers in drug delivery for CVDs includes gene therapy, in order to provide more ideas for the improvement of cardiovascular drugs. In addition, its safety was also discussed in the review.

To ensure the safe use of nanoparticles (NPs) in modern society, it is necessary and urgent to assess the potential toxicity of NPs. Cardiovascular system is required for the systemic distribution of NPs entering circulation. Therefore, the adverse cardiovascular effects of NPs have gained extensive research interests. Metal based NPs, such as TiO2, ZnO and Ag NPs, are among the most popular NPs found in commercially available products. They may also have potential applications in biomedicine, which could increase their contact with cardiovascular systems. This review aimed at providing an overview about the adverse cardiovascular effects of TiO2, ZnO and Ag NPs. We discussed about the bio-distribution of NPs following different exposure routes. We also discussed about the cardiovascular toxicity of TiO2, ZnO and Ag NPs as assessed by in vivo and in vitro models. The possible mechanisms and contribution of physicochemical properties of metal based NPs were also discussed.

Andrographis paniculata Nees is used as a functional food in Japan, Korea, India, and China. Andrographolide, a naturally occurring phytochemical identified in Andrographis paniculata, has been discovered to present anti-inflammatory and anticancer activities. Highly expressed interleukin (IL-8) has been detected in colorectal cancer and is implicated in angiogenesis. However, the effect and molecular mechanisms of IL-8 expression by andrographolide remain obscure in human colorectal cancer cells. The present study was aimed to investigate the effects of andrographolide on TNF-α-induced IL-8 expression and its underlying mechanisms. We found that andrographolide concentration-dependently inhibited TNF-α-induced IL-8 mRNA (2.23 ± 0.15 fold at 20 μM) and protein expression (4.78 ± 0.31 fold at 20 μM) and reduced the IL-8 transcriptional activity (2.59 ± 0.25 fold at 20 μM). TNF-α stimulated the membrane translocation of p47phox to activate reactive oxygen species (ROS)-producing NADPH oxidase (NOX). Furthermore, TNF-α induced Src and MAPKs (Erk1/2, p38 MAPK) phosphorylation, as well as NF-κB and AP-1 binding activities. We found that NF-κB and AP-1 were the critical transcription factors for TNF-α-induced IL-8 expression. Specific inhibitors and mutagenesis studies indicated that Src, Erk1/2, and p38 MAPK are related to TNF-α-induced IL-8. NOX-derived ROS and Src/MAPKs (Erk1/2 and p38 MAPK) functioned as upstream activators of NF-κB and AP-1, respectively. Taken together, andrographolide antagonizes TNF-α-induced IL-8 via inhibition of NADPH oxidase/ROS/NF-κB and Src/MAPKs/AP-1 signaling pathways in HCT116 colorectal cancer cells and then suppresses angiogenesis in the tumor microenvironment.

In this present study, a novel flaxseed gum oligosaccharide (FGOS) was prepared by H2O2 oxidative degradation method followed by physicochemical properties characterization and antiradical activity evaluation. Results indicated that the degradation rate of flaxseed gum is 37.81% under the optimum conditions (i.e., reaction temperature of 120°C, H2O2 concentration of 0.2M and reaction time of 2.0h) and FGOS as a reddish brown semisolid was obtained. Physicochemical properties identification showed that FGOS has a molecular weight of 1047Da and is a typical oligosaccharide which contains uronic acid. Characterizations showed FGOS is acid glycopyranose that consists of rhamnose, fucose, xylose, mannose, arabinose, glucose and galactose with mole percentages of 8.26%, 7.54%, 12.85%, 7.93%, 29.31%, 14.28% and 19.82% respectively. FGOS exhibited good free radical scavenging ability (OH 82.58%, DPPH 52.74% and ABTS 91.29% at most, respectively), suggesting its potent antiradical activity.

The leaves of Psidium guajava L. (PGL) were co-fermented with Monascus anka and bacillus sp . to promote the release of insoluble-bound polyphenol components. The variation tendency of polyphenols contents were tracked during fermentation. Polyphenol compounds from unfermented PGL (UPGL) and fermented PGL (FPGL) were identified by HPLC-TOF-ESI/MS. The antioxidant activities of polyphenols extracts from UPGL and FPGL were determined by different standard methods. The results indicated that total polyphenols and soluble polyphenols contents especially for quercetin were enhanced at the first 8 days of fermentation. Polyphenol extracts from FPGL had higher antioxidant than that from UPGL. Soluble polyphenol extracts exhibited higher antioxidant activity and protective effect against Fenton-induced DNA oxidative damage compared to insoluble-bound polyphenol extracts. This microbial co-fermentation way significantly increased the antioxidant capacities of soluble polyphenols from PGL. Our study provided a new way to upgrade polyphenols or other bioactive compounds with higher health beneficial effects.

The flavonoids (POFs) from the leaves of Platycladus orientalis (L.) Franco were purified using six different macroporous adsorption resins including polar resins NKA-9 and ADS-F8, semi-polar resins ADS-17 and AB-8, and non-polar resins D101 and ADS-5. Among semi-polar resins, AB-8 demonstrated the best adsorption and desorption capacities with an adsorption ratio of 86% and a desorption ratio of 52%. According to the Simultaneous Thermogravimetry-Differential Scanning Calorimetry (STA/TG-DSC) analysis, POFs showed three thermally decomposed temperatures (347.6 °C, 437.5 °C and 494.8 °C). The main flavonoids in POFs were identified as esculin, amentoflavone, glabridin, and afromosin. Meanwhile, POFs in the dosage range of 25 to 400 μg mL-1 showed a significant anti-inflammatory effect on lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophage cells, which could inhibit the secretion of NO, IL-6, and TNF-α through the inhibition of inflammatory-related gene expressions.

International audience; Echinococcosis is a zoonotic infection caused by cestode species of the genus Echinococcus, with limited treatment options. It is urgent to develop new anti-hydatid agent. In this paper, we reported anacardic acid (AA), a natural product isolated from the Brazilian cashew-nut shell liquid, which presented a high activity against metacestodes of Echinococcus multilocularis (E. multilocularis) and Echinococcus granulosus sensu stricto (E. granulosus s.s.) in vitro and in vivo. AA exerted a better efficacy on E. granulosus s.s. protoscoleces and E. multilocularis metacestodes than that of albendazole (ABZ) and dihydroartemisinin (DHA) in vitro, and an inhibition on the growth of Echinococcus metacestode as effective as ABZ in vivo. Moreover, we also found that one of the mechanisms of AA against Echinococcus could be the suppression of angiogenesis on/in the metacestode mass through inhibiting vascular endothelial growth factor (VEGF)—induced signalling pathways. This work finds that AA is a new promising potential candidate drug for echinococcosis treatment.

Hydrogel is a new class of functional polymer materials with a promising potential in the biomedical field. The purpose of this article is to review recent advancements in several types of biomedical hydrogels, including conductive hydrogels, injectable hydrogels, double network hydrogels, responsive hydrogels, nanocomposite hydrogels, and sliding hydrogels. In comparison with traditional hydrogels, these advanced hydrogels exhibit significant advantages in structure, mechanical properties, and applications. The article focuses on different methods used to prepare advanced biomedical hydrogels and their diversified applications as drug delivery systems, wound dressings, biosensors, contact lenses, and tissue replacement. These advances are rapidly overcoming current limitations of hydrogels, and we anticipate that further research will lead to the development of advanced hydrogels with ubiquitous roles in biomedicine and tissue replacement and regeneration.

The anti-digestibility and anti-oxidation of propyl gallate (PG) complexion with rice starch was improved by a twin-screw system under hot-melt extrusion. The relationship of digestibility, predicted glycemic index (pGI), and antioxidant activity in the multi-structures of the complexes were studied in our work. The results suggested that the extruded rice starch/propyl gallate (ERS/PG) complexes showed increases in slowly digestible starch (6.6%−8.9%) and resistant starch (11.2%−25.7%) contents and a decline in pGI (80.3%−74.0%), although the anti-oxidation was significantly increased. Moreover, the addition of PG complexation with hot-melt extrusion diminished the occurrence of double helical and A-type crystalline structures while increasing the prevalence of single helical and V-type crystalline structures, which is consistent with the increases in breakdown viscosity (ηbd), R1045/1022 and fractal dimension (α) and decrease of correlation length (ξ) of ERS/PG with increasing PG content. Interestingly, the long-order structure (single helical and V-type crystalline structure) and short-order structure (indicated by R1045/1022, α, and ξ) of the complexes exhibited positive correlations with digestibility. These points indicate that the ordered structure of the ERS/PG complexes plays the dominant role in determining starch digestibility, thereby allowing it to serve as a carrier to deliver PG to the human lower gastrointestinal tract and achieve the goal of increasing strong antioxidant activity. Taken together, the results show that compounds with PG formed under hot-melt extrusion can improve the synergism of starch digestion and anti-oxidation, thereby improving the postprandial glucose response and oxidative stress.

In the present study, eleven glutathione-derived peptides, including Glu-Cys-His, Pro-Leu-Gly, Pro-Cys-Gly, Phe-Lys-Leu, Leu-His-Gly, Lys-Leu-Glu, Lys-Val-His, Tyr-Glu-Gly, Tyr-His-Leu, Gly-Glu-Leu and Gly-Pro-Glu, were designed. The antioxidant activity of these peptides was investigated by single-electron-transfer (SET) reaction based assays (DPPH radical scavenging ability and reducing power), hydrogen-atom-transfer (HAT) reaction based assays (linoleic autoxidation inhibition activity, ORAC and TEAC) and hydroxyl radical scavenging activity assay. The relationship between the chemical structure and antioxidant activities of the synthetic peptides was analyzed by quantitative structure–activity relationship (QSAR) modeling. Results showed that the amino acids next to C-terminal regions played a much more pivotal role in having high antioxidant activity than those in N-terminal regions. Besides, the difference in free radical category as well as solvent system applied in the antioxidant assay methods could result in different conclusions on the relationship between physicochemical properties (hydrophobicity, steric property and electronic property) and antioxidant activity. The amino acid with high hydrophobic property and steric property in the N-terminal also contributed to the high antioxidant activity of the glutathione-derived peptides.

With lower cell toxicity and higher specificity, novel vaccines have been greatly developed and applied to emerging infectious and chronic diseases. However, due to problems associated with low immunogenicity and complicated processing steps, the development of novel vaccines has been limited. With the rapid development of bio-technologies and material sciences, nanomaterials are playing essential roles in novel vaccine design. Incorporation of nanomaterials is expected to improve delivery efficiency, to increase immunogenicity, and to reduce the administration dosage. The purpose of this review is to discuss the employment of nanomaterials, including polymeric nanoparticles, liposomes, virus-like particles, peptide amphiphiles micelles, peptide nanofibers and microneedle arrays, in vaccine design. Compared to traditional methods, vaccines made from nanomaterials display many appealing benefits, including precise stimulation of immune responses, effective targeting to certain tissue or cells, and desirable biocompatibility. Current research suggests that nanomaterials may improve our approach to the design and delivery of novel vaccines.

The existence of blood-brain barrier (BBB) hampers the effective treatment of central nervous system (CNS) diseases. Almost all macromolecular drugs and more than 98% of small molecule drugs cannot pass the BBB. Therefore, the BBB remains a big challenge for delivery of therapeutics to the central nervous system. With the structural and mechanistic elucidation of the BBB under both physiological and pathological conditions, it is now possible to design delivery systems that could cross the BBB effectively. Because of their advantageous properties, nanoparticles have been widely deployed for brain-targeted delivery. This review paper presents the current understanding of the BBB under physiological and pathological conditions, and summarizes strategies and systems for BBB crossing with a focus on nanoparticle-based drug delivery systems. In summary, with wider applications and broader prospection the treatment of brain targeted therapy, nano-medicines have proved to be more potent, more specific and less toxic than traditional drug therapy.

Hydrogels have been widely studied in various biomedical applications, such as tissue engineering, cell culture, immunotherapy and vaccines, and drug delivery. Peptide-based nanofibers represent a promising new strategy for current drug delivery approaches and cell carriers for tissue engineering. This review focuses on the recent advances in the use of self-assembling engineered β-sheet peptide assemblies for biomedical applications. The applications of peptide nanofibers in biomedical fields, such as drug delivery, tissue engineering, immunotherapy, and vaccines, are highlighted. The current challenges and future perspectives for self-assembling peptide nanofibers in biomedical applications are discussed.

The structure and bioactivity of a novel polysaccharide from Platycladus orientalis (L.) Franco leaves (POP2) were investigated in the present study. Structure characterization demonstrated that the average molecular weight of POP2 was 9.69 kDa and consisted of arabinose (14.39%), mannose (10.24%), glucose (63.95%) and galactose (11.42%). The main linkage types of POP2 consisted of (1→4)-linked α- d -Glc and (1→6)-linked α- d -Glc based on methylation and NMR analysis. Bioactivity evaluation showed that POP2 could effectively promote the secretion of inflammatory cytokines (IL-6 and TNF-α), as well as the anti-inflammatory cytokines (IL-10) in LPS-induced cells. Besides, the secretion of NO was significantly inhibited by POP2 in M1 model. POP2 could enhance the level of inflammatory cytokines (NO, IL-6 and TNF-α), while the secretion of the anti-inflammatory cytokine TGF-β was markedly suppressed in IL-4 induced cells. Our work attempted to elucidate the regulation of macrophage polarization and support the potential application of POP2 as bioactive ingredient for functional foods.

The urokinase-type plasminogen activator receptor (uPAR), a glycoprotein localized on the cell surface with a glycosylphosphatidylinositol anchor, plays a crucial role in cell invasion, and the metastasis of several cancers, including bladder cancer, and its expression are significantly negatively correlated with patient survival rates. Apigenin, a naturally produced phytochemical compound found in fruits, vegetables, and plant leaves, has been shown to mediate a variety of cancer-metastasis-related molecules in various cancers. The effect of apigenin on uPAR expression is still unknown. In this study, we examined the effects of apigenin on IL-1β-induced uPAR expression and investigated its potential mechanisms. We discovered in this study that IL-1β could remarkably induce uPAR expression in bladder cancer T24 cells and that apigenin-inhibited IL-1β could induce uPAR expression concentration-dependently. Interestingly, NF-κB and AP-1 transcription factors were critically required for IL-1β-induced high uPAR expression. Apigenin suppressed the transcriptional activity of both AP-1 and NF-κB by inhibiting ERK1/2 and JNK signaling pathways. These results suggest that apigenin can exert anti-invasion effects by inhibiting uPAR expression via mediating (ERK1/2, JNK)/AP-1 and (ERK1/2, JNK)/NF-κB signaling pathways in human T24 cells. Our present study generated novel and valuable biological insight into anti-invasion through treatment with a small native compound.

To ensure the safe use of nanoparticles (NPs) in modern society, it is necessary and urgent to assess the potential toxicity of NPs. Cardiovascular system is required for the systemic distribution of NPs entering circulation. Therefore, the adverse cardiovascular effects of NPs have gained extensive research interests. Metal based NPs, such as TiO

A new water-soluble polysaccharide (FVP1) was extracted from Flammulina velutipes by traditional method “water extraction and alcohol precipitation” and purified by column chromatography. Physicochemical characterization showed that FVP1 was a homogeneous polysaccharide with a relative molecular weight of 54.78 kDa. It is composed of mannose (7.74%), glucose (70.41%), and galactose (16.38%). FVP1 (1000 mg/mL) possessed significant immune activity by increasing the secretion of nitric oxide (NO), tumour necrosis factor-α (TNF-α) (3183 ± 133.84 pg/mL), interleukin (IL)-6 (1133.21 ± 39.05 pg/mL), and IL-12 (579.96 ± 74.53 pg/mL) in macrophages. Furthermore, FVP1 showed significant hepatitis B surface antibody (anti-HBV) activity through reducing the expression of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA replication. These results suggest a novel role for FVP1 to be applied as an immunomodulators in dietary supplements to prevent HBV infection.

The UL49 ORF of human cytomegalovirus (HCMV) is essential for viral replication; conserved among all herpes viruses; however, the function is unclear. Once the UL49 ORF was precisely deleted from the start to stop codon, the mutant did not yield infectious progeny. In this study, we find out many alternatively processed ESTs in UL49 locus in HCMV-infected cells, in which there are two novel transcription termination sites in UL49 locus. Most of these ESTs are rare transcripts that contain directed repeat sequences in the intron splicing regions. There is a typical GU-AG intron splicing site in UL49Y transcripts. The 1847 bp UL49Y cDNA spans an ORF from 335 to 1618 and encodes a putative protein of 427 amino acids with a predicted molecular mass of 47.1 kDa. All the new EST sequences and UL49Y cDNA sequence have been deposited in the GenBank database (GenBank Accession nos. GW314860-GW314900 and GU376796). This study provides us with very important clues for revealing the importance of the UL49 locus alternative splicing.