A Green Synthesis of Au-Ag Alloy Nanoparticles using Polydopamine Chemistry: Evaluation of their Anticancer Potency Towards Both MCF-7 Cells and their Cancer Stem Cells Subgroup.

BACKGROUND: Limited chemotherapy efficacy and cancer stem cells (CSCs)-induced therapeutic resistance are major difficulties for tumour treatment. Adopting more efficient therapies to eliminate bulk-sensitive cancer cells and resistant CSCs is urgently needed. METHODS: Based on the potential and functional complementarity of gold and silver nanoparticles (AuNPs or AgNPs) on tumour treatment, bimetallic NPs (alloy) have been synthesized to obtain improved or even newly emerging bioactivity from a combination effect. This study reported a facile, green and economical preparation of Au-Ag alloy NPs using biocompatible polydopamine (PDA) as a reductant, capping, stabilizing and hydrophilic agent. RESULTS: These alloy NPs were quasi-spherical with rough surfaces and recorded in diameters of 80 nm. In addition, these alloy NPs showed good water dispersity, stability and photothermal effect. Compared with monometallic counterparts, these alloy NPs demonstrated a dramatically enhanced cytotoxic/pro-apoptotic/necrotic effect towards bulk-sensitive MCF-7 and MDA-MB-231 cells. The underlying mechanism regarding the apoptotic action was associated with a mitochondria-mediated pathway, as evidenced by Au3+/Ag+ mediated Mitochondria damage, ROS generation, DNA fragmentation and upregulation of certain apoptotic-related genes (Bax, P53 and Caspase 3). Attractively, these Au-Ag alloy NPs showed a remarkably improved inhibitory effect on the mammosphere formation capacity of MCF-7 CSCs. CONCLUSION: All the positive results were attributed to incorporated properties from Au, Ag and PDA, the combination effect of chemotherapy and photothermal therapy and the nano-scaled structure of Au-Ag alloy NPs. In addition, the high biocompatibility of Au-Ag alloy NPs supported them as a good candidate in cancer therapy.

Fractional extraction of lignin from coffee beans with low cytotoxicity, excellent anticancer and antioxidant activities.

Lignin, a biopolymer generated from renewable resources, is widely present in terrestrial plants and possesses notable biosafety characteristics. The objective of this work was to assess the edible safety, in vitro antioxidant, and anti-cancer properties of various lignin fractions isolated from commercially available coffee beans often used for coffee preparation. The findings suggest that the phenolic hydroxyl content increased from 3.26 mmol/g (ED70L) to 5.81 mmol/g (ED0L) with decreasing molecular weight, which resulted in more significant antioxidant properties of the low molecular weight lignin fraction. The findings of the study indicate that the viability of RAW 264.7 and HaCaT cells decreased as the quantity of lignin fractions increased. It was observed that concentrations below 200 µg/mL did not exhibit any harmful effects on normal cells. The results of the study demonstrated a significant reduction of cancer cell growth (specifically A375 cells) at a concentration of 800 µg/mL for all lignin fractions, with an observed inhibition rate of 95 %. The results of this study indicate that the lignin extracts derived from coffee beans exhibit significant potential in mitigating diseases resulting from excessive radical production. Furthermore, these extracts show promise as natural antioxidants and anti-cancer agents.

The interaction study of soluble pectin fiber and surimi protein network from silver carp (Hypophthalmichthys molitrix) based on a new prediction model.

Pure surimi of silver carp (Hypophthalmichthys molitrix) cannot meet the texture requirements in novel 3D printing of food. In this work, the effect mechanism of adding soluble pectin fiber on the quality of surimi was studied at molecular scale, and the interaction has been discussed by a novel prediction model. In comparison with pure surimi, pH and water-holding capacity decreased with increasing pectin, and texture properties improved. The storage modulus firstly rose and then decreased, reaching a maximum value of 15012 Pa at 0.5 % pectin addition. The thermal transition temperature of myosin was moved from 52.13 to 49.80 °C. Pectin extended the T22 relaxation time, suggesting a decrease in immobilized water. A new Time-series prediction model and interaction analysis further explored the intrinsic correlation of various parameters of surimi with different pectin additions. This work contributes to add our understanding of pectin application in surimi products in future special dietary food.

A New Gold Nanoparticles and Paclitaxel Co-Delivery System for Enhanced Anti-Cancer Effect Through Chemo-Photothermal Combination.

Limited chemotherapeutic efficiency, drug resistance and side effect are primary obstacles for cancer treatment. The development of co-delivery system with synergistic treatment modes should be a promising strategy. Here, we fabricated a multi-functionalized nanocarrier with a combination of chemotherapeutic agent and gold nanoparticles (AuNPs), which could integrate chemo-photothermal therapy and improve entire anti-cancer index. Particularly, Paclitaxel nanocrystals (PTX NC) were first fabricated as a platform, on surface of which AuNPs were decorated and polydopamine (PDA) layer act as capping, stabilizing and hydrophilic agents for PTX NC, providing a bridge connecting AuNPs to PTX. These AuNPs decorated PTX NC exhibited good physico-chemical properties like optimal sizes, stability and photothermal efficiency. Compared to other PTX formulations, they displayed considerably improved biocompatibility, selectivity, intracellular uptake, cytotoxicity, apoptosis induction activity and P-glycoprotein (Pgp) inhibitory capability, owing to a synergistic/ cooperative effect from AuNPs, PTX and NIR treatment, photothermal-triggered drug release and nano-scaled structure. Mitochondria-mediated signaling pathway is underlying mechanism for cytotoxic and apoptotic effect from AuNPs decorated PTX NC, in terms of Mitochondria damage, a loss of Mitochondrial membrane potential, intensified oxidative stress, DNA breakage, Caspase 3 activation, up-regulated expression in pro-apoptotic genes like p53, Caspase 3 and Bax and down-regulated level in anti-apoptotic gene like Bcl-2.

Gold Nanoparticle-Decorated Drug Nanocrystals for Enhancing Anticancer Efficacy and Reversing Drug Resistance Through Chemo-/Photothermal Therapy.

Limited chemotherapeutic efficiency, drug resistance, and side effects are primary obstacles for cancer treatment. The development of co-delivery systems with synergistic treatment modes should be a promising strategy. Here, we fabricated a multifunctionalized nanocarrier with a combination of chemotherapeutic agents and gold nanoparticles (AuNPs), which could integrate chemo-photothermal therapy, thus enhancing overall anticancer efficacy, sensitizing drug-resistant cancer cells, and diminishing cancer stem cells (CSCs). To be specific, camptothecin nanocrystals (CPT NCs) were prepared as a platform, on the surface of which AuNPs were decorated and a hyaluronic acid layer acted as capping, stabilizing, targeting, and hydrophilic agents for CPT NCs, and reducing agents for AuNPs, providing a bridge connecting AuNPs to CPT. These AuNP-decorated CPT NCs exhibited good physico-chemical properties such as optimal sizes, payload, stability, and photothermal efficiency. Compared to other CPT formulations, they displayed considerably improved biocompatibility, selectivity, intracellular uptake, cytotoxicity, apoptosis induction activity, Pgp inhibitory capability, and anti-CSC activity, owing to a synergistic/cooperative effect from AuNPs, CPT, near-infrared treatment, pH/photothermal-triggered drug release, and nanoscaled structure. A mitochondrial-mediated signaling pathway is the underlying mechanism for cytotoxic and apoptotic effects from AuNP-decorated CPT NCs, in terms of mitochondrial dysfunction, intensified oxidative stress, DNA fragmentation, caspase 3 activation, upregulation of proapoptotic genes such as p53, Bax, and caspase 3, and lower levels of antiapoptotic Bcl-2.

The isolation, structural features and biological activities of polysaccharide from Ligusticum chuanxiong: A review.

Ligusticum chuanxiong, the dried rhizome of Ligusticum chuanxiong Hort, has been widely applied in traditional Chinese medicine for treating plague, and it has appeared frequently in the prescriptions against COVID-19 lately. Ligusticum chuanxiong polysaccharide (LCPs) is one of the effective substances, which has various activities, such as, anti-oxidation, promoting immunity, anti-tumor, and anti-bacteria. The purified fractions of LCPs are considered to be pectic polysaccharides, which are mainly composed of GalA, Gal, Ara and Rha, and are generally linked by α-1,4-d-GalpA, α-1,2-l-Rhap, α-1,5-l-Araf, ß-1,3-d-Galp and ß-1,4-d-Galp, etc. The pectic polysaccharide shows an anti-infective inflammatory activity, which is related to antiviral infection of Ligusticum chuanxiong. In this article, the isolation, purification, structural features, and biological activities of LCPs in recent years are reviewed, and the potential of LCPs against viral infection as well as questions that need future research are discussed.

An integration study of microalgae bioactive retention: From microalgae biomass to microalgae bioactives nanoparticle.

Microalgae metabolites include biologically active compounds with therapeutic effects such as anticancer, anti-inflammatory and immunomodulation effects. One of the most recent focuses is on utilizing microalgae lipid-based biologically active compounds in food applications. However, most microalgae biological active compounds in their natural forms have common drawbacks like low solubility, low physicochemical stability and strong susceptibility to degradation, which significantly limits their application in foods, therefore, it is important to find solutions to retain their functional properties. In the present work, a comprehensive review on multi-product biorefinery was carried out from upstream processing stage to downstream processing stage, and identify critical processes and factors that impact bioactive material acquisition and retention. Furthermore, since nanoencapsulation technology emerges as an effective solution for microalgae nutraceutical product's retention, this work also focus on the nanoparticle perspective and comprehensively reviews the current nanoencapsulation solutions of the microalgae bioactive extract products. The aim is to depict advances in the formulations of microalage bioactive nanoparticles and provide a critical analysis of the reported nanoparticle formation. Overall, through the investigation of microalgae from biomass to bioactive nanoparticles, we aim to facilitate microalgae nutraceuticals incorporation as high value-added ingredients in more functional food that can improve human health.

Gut microbiota from patients with arteriosclerotic CSVD induces higher IL-17A production in neutrophils via activating RORγt.

The intestinal microbiota shape the host immune system and influence the outcomes of various neurological disorders. Arteriosclerotic cerebral small vessel disease (aCSVD) is highly prevalent among the elderly with its pathological mechanisms yet is incompletely understood. The current study investigated the ecology of gut microbiota in patients with aCSVD, particularly its impact on the host immune system. We reported that the altered composition of gut microbiota was associated with undesirable disease outcomes and exacerbated inflammaging status. When exposed to the fecal bacterial extracts from a patient with aCSVD, human and mouse neutrophils were activated, and capacity of interleukin-17A (IL-17A) production was increased. Mechanistically, RORγt signaling in neutrophils was activated by aCSVD-associated gut bacterial extracts to up-regulate IL-17A production. Our findings revealed a previously unrecognized implication of the gut-immune-brain axis in aCSVD pathophysiology, with therapeutic implications.

Hyaluronic Acid-Coated Camptothecin Nanocrystals for Targeted Drug Delivery to Enhance Anticancer Efficacy.

Tumor-targeted drug delivery via chemotherapy is very effective on cancer treatment. For potential anticancer agent such as Camptothecin (CPT), high chemotherapeutic efficacy and accurate tumor targeting are equally crucial. Inspired by special CD44 binding capability from hyaluronic acid (HA), in this study, novel HA-coated CPT nanocrystals were successfully prepared by an antisolvent precipitation method for tumor-targeted delivery of hydrophobic drug CPT. These HA-coated CPT nanocrystals demonstrated high drug loading efficiency, improved aqueous dispersion, prolonged circulation, and enhanced stability resulting from their nanoscaled sizes and hydrophilic HA layer. Moreover, as compared to crude CPT and naked CPT nanocrystals, HA-coated CPT nanocrystals displayed dramatically enhanced in vitro anticancer activity, apoptosis-inducing potency against CD44 overexpressed cancer cells, and lower toxic effect toward normal cells due to pH-responsive drug release behavior and specific HA-CD44 mediated endocytosis. Additionally, HA-coated CPT nanocrystals performed fairly better antimigration activity and biocompatibility. The possible molecular mechanism regarding this novel drug formulation might be linked to intrinsic mitochondria-mediated apoptosis by an increase of Bax to Bcl-2 ratio and upregulation of P53. Consequently, HA-coated CPT nanocrystals are expected to be an effective nanoplatform in drug delivery for cancer therapy.

Xanthophyllomyces dendrorhous-Derived Astaxanthin Regulates Lipid Metabolism and Gut Microbiota in Obese Mice Induced by A High-Fat Diet.

Astaxanthin is an important antioxidant with many biological activities such as anti-tumor, anti-obesity, cardioprotective, and immuno-modulatory activities. Most of these biological activities are derived from (3S,3'S)-astaxanthin, while the activities of (3R,3'R)-astaxanthin are rarely reported. The purpose of this study was to investigate the effect of (3R,3'R)-astaxanthin on lipid metabolism and gut microbiota in mice fed with a high-fat diet. In this work, 40 male C57BL/6 mice were divided into 8 groups fed a high-fat diet supplemented or not with (3R,3'R)-astaxanthin or Xanthophyllomyces dendrorhous for 8 weeks. The weight gain, energy intake, fat index, plasma triacylglycerol and cholesterol, liver triacylglycerol and cholesterol, and gut microbiota were determined. The results showed that the addition of (3R,3'R)-astaxanthin/X. dendrorhous to the high-fat diet as a supplement prevented weight gain, reduced plasma and liver triacylglycerol, and decreased plasma and liver total cholesterol. The addition of (3R,3'R)-astaxanthin/X. dendrorhous also regulated the gut microbiota of the mice, which optimized the ratio of Bacteroides to Firmicutes and increased the content of Verrucomicrobia, especially Akkermansia. The changes in the gut microflora achieved a healthier structure, thus reducing the incidence of obesity. Thus (3R,3'R)-Astaxanthin has the function of regulating lipid metabolism and gut microbiota to prevent obesity caused by a high-fat diet. The production strain of (3R,3'R)-astaxanthin, X. dendrorhous, has the same function as astaxanthin in preventing obesity caused by a high-fat diet, which reflects its potential ability as a probiotic drug.

Influence of Acid Treatment on the Loading and Release Behavior of Halloysite with 2-Mercaptobenzothiazole.

Halloysite nanotubes (HNTs) are natural clay minerals with a tubular structure. They have attracted considerable attention as a potential nanocontainer due to their abundance, biocompatibility and nontoxicity. In this study, HNTs were handled with H2SO4 at 70 °C. The morphology and structure of these acid-treated and original HNTs were investigated by scanning electron microscopy (SEM), energy dispersion spectrum (EDS), transmission electron microscope (TEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR), and their specific surface area was determined by automatic gas adsorption analyzer. The loading efficiency and release behavior of acid-treated HNTs for 2-Mercaptobenzothiazole (MBT) were investigated by UV-vis spectrophotometer. Results show that acid-treated HNTs retained their tubular structure, but their internal diameter expanded by 35-37 nm after 32 h of acid treatment. After 72 h of acid treatment, HNTs can be transferred into amorphous silica nanotubes. Moreover, the specific surface area of these HNTs samples initially increased with the increase in acid treatment time but then started to decrease after 32 h. The specific surface area of acid-treated HNTs at 32 h can reach 251.6 m2/g, which was much higher than that for untreated HNTs (55.3 m2/g). In addition, the loading capacity of acid-treated HNTs can reach 32.1% for HNTs-32, which is about three times higher than that of original HNTs. The acid treatment has slight effect on the release behavior.

Curcumin attenuates murine lupus via inhibiting NLRP3 inflammasome.

Despite rapid progress in the understanding of systemic lupus erythematosus (SLE), there is still an urgent need for novel and more effective interventions. Curcumin, a natural polyphenol compound, has been shown to be anti-inflammatory in various disorders. In this study, we investigated the potential therapeutic value of curcumin in SLE. Lupus-prone female MRL/lpr mice were treated with curcumin. The development and extent of nephritis were assessed by monitoring proteinuria and by histologic analysis. Serum anti-dsDNA levels were measured by enzyme-linked immunosorbent assay. Kidney samples were analyzed by Western blot. In vitro, mouse podocytes were used for investigation in the presence of mouse anti-dsDNA antibody-positive (anti-dsDNA+) serum. Curcumin treatment dramatically decreased proteinuria and renal inflammation. Serum anti-dsDNA levels and spleen size were also reduced by curcumin. In addition, curcumin reduced NLRP3 inflammasome activation in lupus-prone mice. In vitro, curcumin significantly inhibited anti-dsDNA+ serum induced expression of NLRP3 inflammasome in podocytes. Overall, these data demonstrate the potential use of curcumin in SLE treatment.

Combined mutagenesis of Rhodosporidium toruloides for improved production of carotenoids and lipids.

OBJECTIVES: To improve production of lipids and carotenoids by the oleaginous yeast Rhodosporidium toruloides by screening mutant strains. RESULTS: Upon physical mutagenesis of the haploid strain R. toruloides np11 with an atmospheric and room temperature plasma method followed by chemical mutagenesis with nitrosoguanidine, a mutant strain, R. toruloides XR-2, formed dark-red colonies on a screening plate. When cultivated in nitrogen-limited media, XR-2 cells grew slower but accumulated 0.23 g lipids/g cell dry wt and 0.75 mg carotenoids/g CDW. To improve its production capacity, different amino acids and vitamins were supplemented. p-Aminobenzoic acid and tryptophan had beneficial effects on cell growth. When cultivated in nitrogen-limited media in the presence of selected vitamins, XR-2 accumulated 0.41 g lipids/g CDW and 0.69 mg carotenoids/g CDW. CONCLUSIONS: A mutant R. toruloides strain with improved production profiles for lipids and carotenoids was obtained, indicating its potential to use combined mutagenesis for a more productive phenotype.

The Chemical Constituents and Pharmacological Actions of Cordyceps sinensis.

Cordyceps sinensis, also called DongChongXiaCao (winter worm, summer grass) in Chinese, is becoming increasingly popular and important in the public and scientific communities. This study summarizes the chemical constituents and their corresponding pharmacological actions of Cordyceps sinensis. Many bioactive components of Cordyceps sinensis have been extracted including nucleoside, polysaccharide, sterol, protein, amino acid, and polypeptide. In addition, these constituents' corresponding pharmacological actions were also shown in the study such as anti-inflammatory, antioxidant, antitumour, antiapoptosis, and immunomodulatory actions. Therefore can use different effects of C. sinensis against different diseases and provide reference for the study of Cordyceps sinensis in the future.

Effects of carbohydrate sources on biosorption properties of the novel exopolysaccharides produced by Arthrobacter ps-5.

The crude exopolysaccharides (EPSs) were obtained from Arthrobacter ps-5 fermentation using various carbohydrate sources followed by centrifugation, ethanol precipitation, and the isolated EPSs were further deproteinized and lyophilized. Carbohydrates from various sources resulted in different yield of EPSs from the fermentation and different molecular weight of EPSs. A maximum yield of 0.27 mg/g was achieved by using the culture medium supplemented with sucrose. The EPS produced by glucose-supplemented medium had the maximum content of acidic polysaccharides, subsequently presented the highest biosorption capacity for Cu(2+) and Pb(2+) at 257.9 mg/g and 331.8 mg/g, respectively. The ratio of acidic to neutral polysaccharides presented in EPSs was a key factor to explicate the biosorption mechanism, the higher the ratio, the stronger the biosorption capacity.

Presence of photoluminescent carbon dots in Nescafe® original instant coffee: applications to bioimaging.

The presence of the carbon dots (C-dots) in food is a hotly debated topic and our knowledge about the presence and the use of carbon dots (C-dots) in food is still in its infancy. We report the finding of the presence of photoluminescent (PL) C-dots in commercial Nescafe instant coffee. TEM analysis reveals that the extracted C-dots have an average size of 4.4 nm. They were well-dispersed in water and strongly photoluminescent under the excitation of ultra-violet light with a quantum yield (QY) about 5.5%, which were also found to possess clear upconversion PL properties. X-ray photoelectron spectroscopy characterization demonstrates that the C-dots contain C, O and N three elements with the relative contents ca. 30.1, 62.2 and 7.8%. The X-ray diffraction (XRD) analysis indicates that the C-dots are amorphous. Fourier-transform infrared (FTIR) spectra were employed to characterize the surface groups of the C-dots. The C-dots show a pH independent behavior by varying the pH value from 2 to 11. The cytotoxicity study revealed that the C-dots did not cause any toxicity to cells at a concentration as high as 20 mg/mL. The C-dots have been directly applied in cells and fish imaging, which suggested that the C-dots present in commercial coffee may have more potential biological applications.

Roles of tetrahydrobiopterin in promoting tumor angiogenesis.

Nitric oxide (NO), which is derived from endothelial NO synthase (eNOS), provides crucial signals for angiogenesis in the tumor microenvironment. Tetrahydrobiopterin (BH4) is an absolute requirement for eNOS activity. In this study, we investigated whether this activation is both maintained by a wild-type Ras/phosphatidylinositol 3-kinase (PI3K)/Akt-positive feedback loop in endothelial cells and affects tumor angiogenesis. We found that supplementation of BH4 (via the pterin salvage pathway with Sep) increased Akt/eNOS phosphorylation in both human eNOS-transfected COS-7 cells and endothelial cells concomitant with increases in NO production, cell proliferation, migration, and tube formation. This augmentation was abrogated by a PI3K inhibitor. Sepiapterin (Sep) also increased GTP-bound wild-type Ras and PI3K/Akt/eNOS activation, which was prevented by the eNOS inhibitor, Nω-Nitro-L-arginine methyl ester (L-NAME). Furthermore, expression of GTP cyclohydrolase I (the rate-limiting enzyme in de novo BH4 synthesis) under doxycycline control potentiated in vivo tumorigenesis, tumor cell proliferation, as well as angiogenesis. Conversely, both switching off GTP cyclohydrolase I expression as well as inhibiting its enzymatic activity significantly decreased eNOS expression and tumor vascularization. This study demonstrates an important role for BH4 synthesis in angiogenesis by the activation of eNOS for NO production, which is maintained by a PI3K/Akt-positive feedback loop through effects on wild-type Ras in endothelial cells. Our findings suggest that BH4 synthesis may be a rational target for antiangiogenesis therapy for tumors.

Glabridin from Chinese herb licorice inhibits fatigue in mice.

The inhibiting effect of glabridin from Chinese herb Licorice on fatigue was investigated in male BALB/c mice. Mice were divided into the following 4 experimental groups: control group (CG), low dose group (LG), middle dose group (MG) and high dose group (HG,). The control group was given 0.5% Tween 80 solution and the treatment groups (LG, MG, HG) were given various doses of glabridin (5, 10, 20 mg/kg) for 28 consecutive days. Body mass, blood lactic acid (BLA), serum blood urea nitrogen (BUN), liver glycogen and muscle glycogen concentrations in mice were determined. Results showed that glabridin significantly inhibited fatigue, which extended the exhaustive exercise time of mice, effectively delayed the elevation of blood lactic acid and increase in the storage of liver and muscle glycogen.