Pt,P-codoped carbon nitride nanoenzymes for fluorescence and colorimetric dual-mode detection of cholesterol.

Cholesterol is an important lipid compound found in a variety of foods, and its level in human blood is closely related to human health. Therefore, development of rapid and accurate POCT (point-of-care testing) methods for cholesterol detection is crucial for assessing food quality and early diagnosis of diseases, in particular, in a resource-limited environment. In this study, a smartphone-assisted colorimetric biosensor is constructed based on platinum,phosphorus-codoped carbon nitride (PtCNP2) for the rapid detection of cholesterol. Phosphorus-doped carbon nitride is prepared by thermal annealing of urea and NH4PF6, into which platinum is atomically dispersed by thermal refluxing. The obtained PtCNP2 exhibits an excellent peroxidase-like activity under physiological pH, whereby colorless o-phenylenediamine (OPD) is oxidized to colored 2,3-diaminophenazine (DAP) in the presence of hydrogen peroxide (H2O2), which can be produced during the oxidation of cholesterol by cholesterol oxidase. A smartphone-assisted visual sensing system is then constructed based on the color recognition software, and rapid on-site detection of cholesterol is achieved by reading the RGB values. Meanwhile, the generated DAP shows an apparent fluorescence signal and can realize highly sensitive detection of cholesterol by the change of the fluorescence signal intensity. Such a cholesterol sensor exhibits a wide linear detection range of 0.5-600 µg mL-1 and a low detection limit of 59 ng mL-1. The practicality of the sensor is successfully demonstrated in the rapid detection of cholesterol in serum and food.

Ginkgo Biflavones Cause p53 Wild-Type Dependent Cell Death in a Transcription-Independent Manner of p53.

Ginkgo biloba, as a medicinal plant in both traditional and western medicine, emerged as a potential therapeutic agent for the management of a variety of diseases, but ginkgo biflavones (bilobetin, isoginkgetin, and ginkgetin) application in cancer therapy and underlying mechanisms of action remained elusive. In the present study, we identified ginkgo biflavones as potential p53 activators that could enhance p53 protein expression level by inhibiting MDM2 protein expression. At the same time, they induced cell death independent of p53 transcriptional activity. Moreover, ginkgetin was a standout among ginkgo biflavones that reduced the survival of HCT-116 cells by induction of apoptosis and G2/M phase arrest. Furthermore, ginkgo biflavones induced ROS generation significantly, which resulted in ferroptosis. Finally, we provide evidence that ginkgetin strengthened the antitumor effect of fluorouracil (5-FU) in the HCT-116 colon cancer xenograft model. To sum up, ginkgo biflavones represent a new class of p53 activator that depends on the p53 wild-type status and warrants further exploration as potential anticancer agents.

Highland Barley Tea Polyphenols Extract Alleviates Skeletal Muscle Fibrosis in Mice by Reducing Oxidative Stress, Inflammation, and Cell Senescence.

The tea of roasted Highland barley is a cereal-based drink rich in polyphenols. A model of skeletal muscle senescence and fibrosis was constructed using d-galactose-induced C2C12 myotubes, and Highland barley tea Polyphenols (HBP) were extracted for the intervention. We found that HBP effectively alleviated oxidative stress, inflammation, and fibrosis induced by d-galactose-induced skeletal muscle senescence. Also, HBP treatment significantly down-regulated pro-fibrotic genes, inflammation, and oxidative stress levels in a contusion model of senescent mice. Reduced levels of SIRT3 protein was found to be an essential factor in skeletal muscle senescence and fibrosis in both cellular and animal models, while HBP treatment significantly increased SIRT3 protein levels and viability in skeletal muscle. The ability of HBP to mitigate skeletal muscle fibrosis and oxidative stress was significantly reduced after SIRT3 silencing. Together, these results suggest that HBP intervention can significantly alleviate aging-induced oxidative stress, inflammation, and skeletal muscle fibrosis, with the activation of SIRT3 as the underlying mechanism of action.

Polyphenols in Highland Barley Tea Inhibit the Production of Advanced Glycosylation End-Products and Alleviate the Skeletal Muscle Damage.

SCOPE: Highland barley tea is a kind of caffeine-free cereal tea. Previous studies have shown that it is rich in polyphenol flavonoids. Here, the effect of Highland barley tea polyphenols (HBP) on the production of advanced glycosylation end-products and alleviate the skeletal muscle damage is systematically investigated. METHODS AND RESULTS: HBP effectively inhibits the formation of AGEs in vitro, and 12 phenolic compounds are identified. In addition, d-galactose is used to construct a mouse senescence model and intervenes with different doses of HBP. It is found that high doses of HBP effectively inhibit AGEs in serum and flounder muscle species and increased muscle mass in flounder muscle; also, high doses of HBP increase the expression of the mitochondrial functional protein SIRT3 and decrease the expression of myasthenia-related proteins. Furthermore, cellular experiments show that AGEs can significantly increase oxidative stress in skeletal muscle. CONCLUSION: These data indicate that the relationship between the biological activity and HBP properties is relevant since Highland barley can be a potential functional food to prevent AGEs-mediated skeletal muscle damage.

A novel regulatory mechanism of geniposide for improving glucose homeostasis mediated by circulating RBP4.

BACKGROUND: Systemic insulin signal transduction is influenced by the inter-tissue crosstalk, which might be the potential therapeutic strategy for T2DM. Although anti-diabetic function of geniposide has been previously reported, the underlying mechanism was not completely clear in light of the complex pathogenesis of T2DM. PURPOSE: The present experiment is devoted to investigate the potential effects of geniposide on systemic insulin sensitivity mediated by hepatokine-RBP4 in high fat diet (HFD)-fed mice. METHODS: The HFD-fed wild type mice were administered with geniposide (25 or 50 mg/kg/d) by intraperitoneal injection, and the normal saline and Metformin were used as negative control group and positive control group, respectively. After administration for 4 weeks, the food intake, body weight, glucose tolerance tests, insulin tolerance tests and serum biochemical indices were examined, along with insulin signaling pathway-associated proteins and hepatic histomorphological analysis. The liver, gastrocnemius and mouse primary hepatocytes were also harvested for molecular mechanism study. RESULTS: After geniposide treatment for 4 weeks, the blood glucose level was reduced in HFD-fed mice. Furthermore, geniposide treatment improved insulin sensitivity both in the liver and gastrocnemius (GAS). In terms of mechanism, geniposide disturbed circulating RBP4 level including its synthesis, secretion and homeostasis. Moreover, geniposide modified fuel selection and promoted glucose uptake in skeletal muscle and reduced glycogen storage, which were closely related to impaired circulating RBP4 homeostasis, leading to ameliorative systemic insulin sensitivity. CONCLUSION: Our current study proposes a novel regulatory mechanism of geniposide for improving glucose homeostasis through regulating circulating RBP4 level, which also provides new strategies for the prevention and treatment of T2DM.

Wheat bran, as the resource of dietary fiber: a review.

Wheat bran is a major by-product of white flour milling and had been produced in large quantities around the world; it is rich in dietary fiber and had already been used in many products such as whole grain baking or high dietary fiber addition. It has been confirmed that a sufficient intake of dietary fiber in wheat bran with appropriate physiological functions is beneficial to human health. Wheat bran had been considered as the addition with a large potential for improving the nutritional condition of the human body based on the dietary fiber supplement. The present review summarized the available information on wheat bran related to its dietary fiber functions, which may be helpful for further development of wheat bran as dietary fiber resource.

Well-Defined Gold Nanorod/Polymer Hybrid Coating with Inherent Antifouling and Photothermal Bactericidal Properties for Treating an Infected Hernia.

Biomedical device-associated infection (BAI) is a great challenge in modern clinical medicine. Therefore, developing efficient antibacterial materials is significantly important and meaningful for the improvement of medical treatment and people's health. In the present work, we developed a strategy of surface functionalization for multifunctional antibacterial applications. A functionalized polyurethane (PU, a widely used biomedical material for hernia repairing) surface (PU-Au-PEG) with inherent antifouling and photothermal bactericidal properties was readily prepared based on a near-infrared (NIR)-responsive organic/inorganic hybrid coating which consists of gold nanorods (Au NRs) and polyethylene glycol (PEG). The PU-Au-PEG showed a high efficiency to resist adhesion of bacteria and exhibited effective photothermal bactericidal properties under 808 nm NIR irradiation, especially against multidrug-resistant bacteria. Furthermore, the PU-Au-PEG could inhibit biofilm formation long term. The biocompatibility of PU-Au-PEG was also proved by cytotoxicity and hemolysis tests. The in vivo photothermal antibacterial properties were first verified by a subcutaneous implantation animal model. Then, the anti-infection performance in a clinical scenario was studied with an infected hernia model. The results of animal experiment studies demonstrated excellent in vivo anti-infection performances of PU-Au-PEG. The present work provides a facile and promising approach to develop multifunctional biomedical devices.

Shuangxia decoction alleviates p-chlorophenylalanine induced insomnia through the modification of serotonergic and immune system.

As a Traditional Chinese Medicine (TCM), Shuangxia Decoction (SXD) has been used to treat insomnia in oriental countries for more than thousands of years and it presents remarkable clinical effects. However, its active pharmacological fraction and the mechanism of sedative-hypnotic effects have not been explored. In this paper, we investigated active pharmacological fraction and revealed the detailed mechanisms underlying the sedative-hypnotic effects of SXD. It showed that SXD water extract compared to ethanol extract possessed better sedative effects on locomotion activity in normal mice and increased sleep duration in subhypnotic dose of sodium pentobarbital-treated mice. SXD alleviated p-chlorophenylalanine (PCPA) -induced insomnia by increasing the content of 5-HT in cortex [F (4, 55) = 12.67], decreasing the content of dopamine (DA) and norepinephrine (NE). Furthermore, SXD enhanced the expression of 5-HT1A and 5-HT2A receptors in hypothalamic and reduced serum levels of IL-1,TNF-α [F (5, 36) = 15.58]. In conclusion, these results indicated that SXD produced beneficial sedative and hypnotic bioactivities mediated by regulating the serotonergic and immune system.

The up-regulation of two identified wound healing specific proteins-HSP70 and lysozyme in regenerated Eisenia fetida through transcriptome analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Disposed earthworm has been used to treat various common ailments including burns, arthritis, itching, and inflammation for thousands of years in China. As their remarkable ability to fully regenerate in a scar-free manner, regenerated tissue homogenate of amputated Eisenia fetida (E. fetida) have been considered as an excellent wound repair therapy in our previous study. We have demonstrated that regenerated earthworm (G-90') can perform higher wound repair ability to non-regeneration tissue (G-90) through significant promotion of cutaneous wound repair in mice after their administration into wound beds. OBJECTIVE: In the present study, we aimed to reveal the mechanism of G-90' and to explore a potential wound healing accelerated strategy. METHODS AND RESULTS: Two functional proteins- HSP70 and lysozyme in G-90' were confirmed by cross-identification of LC-MS/MS and transcriptome analyses. Followed with semi-quantitative PCR and western blot, their expression were validated to up-regulate in 3-day regenerated tissues (G-90'). CONCLUSION: This study implies the therapeutic potency of G-90' for wound recovery and provides a new strategy to assess other natural materials targeting wound healing with the tail-amputated E .fetida as a model organism.

Defining Acupuncture-Moxibustion: A Delphi Study Protocol.

BACKGROUND: With the worldwide use and modern development of acupuncture-moxibustion, there is disagreement on its basic definition. There has been an obstacle for clinical practice, research, and legislation. Considering this challenge, the World Federation of Acupuncture-Moxibustion Societies proposes to develop the definition and basic scope of acupuncture-moxibustion with a Delphi study. METHODS: A reactive Delphi method will be used to ask a group of experts to rate the relevance and clarity of a predesigned initial item list. This list was generated by the steering committee through a literature review and group discussion. Forty experts will be selected from many disciplines and continents to ensure appropriate representation. Predefined rules will be applied to modify the items until a consensus is achieved. After achieving the consensus on all items through the survey round, the steering committee will form the definition and basic scope of acupuncture-moxibustion by organizing a literal statement with a detailed explanation.

Assessment of contamination source and quality control approach for polycyclic aromatic hydrocarbons in wood-pressed rapeseed oil.

Contamination sources of polycyclic aromatic hydrocarbons (PAHs) in the raw material, oil production and storage processes of wood-pressed rapeseed oil were investigated in this study. The results showed that benzo[a]pyrene (BaP) and PAH4 (sum of BaP, benzo[a]fluoranthene, benzo[b]fluoranthene and chrysene) were unevenly distributed in the kernel (0.56-0.98 and 2.84-8.64 µg/kg, respectively) and hull (1.53-3.17 and 13.49-22.31 µg/kg, respectively) of the rapeseed raw materials. The contents of BaP and PAH4 continuously increased during the process of wood-pressed rapeseed oil, ranging from 2.21 to 10.93 and 9.36 to 40.03 µg/kg, thus demonstrating that a wide range of pollution sources of PAHs existed for the test wood-pressed rapeseed oils. The initial temperature and time of roasting should be controlled at <210°C and <60 min, due to the generation of PAHs in rapeseed by over-roasting. In addition, contact tools and substance such as lubricating oil (from the mill), heat-transfer oil (from roasting machine), rubber gaskets and straws should be properly screened. The BaP and PAH4 of rapeseed placed in the roasting area increased from 0.5 to 2.24 and from 2.08 to 9.03 µg/kg, respectively. Therefore, roasting fume control and treatment systems are necessary and the roasting section should be strictly isolated from the other stages. Storage can slightly lower the PAHs amounts in the rapeseed oil, which made the contents of BaP and PAH4 decrease from 27.00 to 24.70 and from 138.63 to 117.58 µg/kg, respectively. Quality control measures of PAHs in wood-pressed rapeseed oil were proposed and implemented, and the final oil products' BaP and PAH4 were kept below 2 and 10 µg/kg, respectively, which meets the European Commission Regulation No. 835/2011.

[The current situation of acupuncture definition in international organizations and legislation of some countries].

Acupuncture is developing rapidly in the world, and more attention is paid on acupuncture in various countries. Because of the cultural differences, there are different views on acupuncture between China and the west, which has brought influence and challenge to the development of acupuncture in the world. Acupuncture-related research is becoming increasingly extensive and complex, but the definition of acupuncture is lack of unified standards. The definition of acupuncture is in urgent need. Based on the analysis of acupuncture definition in the 201 international organizations of 48 countries on five continents and legislation of representative countries, this paper summarized the development status of acupuncture in foreign countries, and put forward that the definition of acupuncture should adopt the model of small connotation and large extension, integrate discipline superiority, expand the scope of acupuncture, and focus on the overall situation.

Mouse myosin-19 is a plus-end-directed, high-duty ratio molecular motor.

Class XIX myosin (Myo19) is a vertebrate-specific unconventional myosin, responsible for the transport of mitochondria. To characterize biochemical properties of Myo19, we prepared recombinant mouse Myo19-truncated constructs containing the motor domain and the IQ motifs using the baculovirus/Sf9 expression system. We identified regulatory light chain (RLC) of smooth muscle/non-muscle myosin-2 as the light chain of Myo19. The actin-activated ATPase activity and the actin-gliding velocity of Myo19-truncated constructs were about one-third and one-sixth as those of myosin-5a, respectively. The apparent affinity of Myo19 to actin was about the same as that of myosin-5a. The RLCs bound to Myo19 could be phosphorylated by myosin light chain kinase, but this phosphorylation had little effect on the actin-activated ATPase activity and the actin-gliding activity of Myo19-truncated constructs. Using dual fluorescence-labeled actin filaments, we determined that Myo19 is a plus-end-directed molecular motor. We found that, similar to that of the high-duty ratio myosin, such as myosin-5a, ADP release rate was comparable with the maximal actin-activated ATPase activity of Myo19, indicating that ADP release is a rate-limiting step for the ATPase cycle of acto-Myo19. ADP strongly inhibited the actin-activated ATPase activity and actin-gliding activity of Myo19-truncated constructs. Based on the above results, we concluded that Myo19 is a high-duty ratio molecular motor moving to the plus-end of the actin filament.

Cantharidin, a potent and selective PP2A inhibitor, induces an oxidative stress-independent growth inhibition of pancreatic cancer cells through G2/M cell-cycle arrest and apoptosis.

Cantharidin is an active constituent of mylabris, a traditional Chinese medicine. It is a potent and selective inhibitor of protein phosphatase 2A (PP2A) that plays an important role in control of cell cycle, apoptosis, and cell-fate determination. Owing to its antitumor activity, cantharidin has been frequently used in clinical practice. In the present study, we investigated the therapeutic potential of cantharidin in pancreatic cancer. Cantharidin efficiently inhibited the growth of pancreatic cancer cells, but presented a much lighter toxicity effect against normal pancreatic duct cells. It caused G2/M cell-cycle arrest that was accompanied by the down-regulation of cyclin-dependent kinase 1 (CDK1) and up-regulation of p21 expression. It induced apoptosis and elevated the expressions of pro-apoptotic factors tumor necrosis factor-alpha (TNF-alpha), TNF-related apoptosis inducing receptor 1 (TRAILR1), TRAILR2, Bad, Bak, and Bid, and decreased the expression of anti-apoptotic Bcl-2. Activation of caspase-8 and caspase-9 suggested that both extrinsic and intrinsic pathways are involved in the induction of apoptosis. Interestingly, unlike previous studies on other cancer cells, we found that the inhibitory role of cantharidin is independent of oxidative stress in pancreatic cancer cells. Mitogen-activated protein kinases (MAPKs), including ERK, JNK, and p38, were activated after treatment with cantharidin. Inhibition of JNK, but not ERK or p38, alleviated the cytotoxity effect of cantharidin, suggesting cantharidin exerted its anticancer effect through the JNK-dependent way. Hence, in addition to being an attractive candidate compound with therapeutic potential, cantharidin also highlighted the possibility of using PP2A as a therapeutic target for pancreatic cancer treatment.