Preliminary evidence for an influence of exposure to polycyclic aromatic hydrocarbons on the composition of the gut microbiota and neurodevelopment in three-year-old healthy children.

BACKGROUND: During the second and third year after birth the gut microbiota (GM) is subjected to important development. The polycyclic aromatic hydrocarbon (PAH) exposure could influence the GM in animal and early postnatal exposure is associated with neurodevelopment disorder in children. This study was designed to explore the possible influence of the polycyclic aromatic hydrocarbons (PAHs) on the composition of the gut microbiota (GM) and neurodevelopment in a sample of 38 healthy children at the age of 3 years. METHODS: A brief development (Gesell Development Inventory, GDI) and behavior test (Child Behavior Checklist, CBCL) were completed on 3-yr-olds and stool samples were collected for 16S rRNA V4-V5 sequencing. The PAH-DNA adduct in the umbilical cord blood and the urinary hydroxyl PAHs (OH-PAHs) at the age of 12 months were measured as pre- and postnatal PAH exposure, respectively. RESULTS: The most abundant two phyla were Bacteroidetes (68.6%) and Firmicutes (24.2%). The phyla Firmicutes, Actinobacteria, Proteobacteria, Tenericutes, and Lentisphaerae were positively correlated with most domain behaviors of the GDI, whereas the Bacteroidetes, Cyanobacteria, and Fusobacteria were negatively correlated. Correspondingly, the phyla Bacteroidetes, Actinobacteria, and Fusobacteria showed positive correlations with most CBCL core and broadband syndromes, whereas the Firmicutes, Verrucomicrobia, Synergistetes, Proteobacteria and Tenericules were negatively correlated. The OH-PAH levels were not significantly associated with the Firmicutes phylum whereas the Bacteroidetes, Bacteroidia, and Bacteroidales all showed significant negative association with the OH-PAH levels. CONCLUSION: The current findings suggest that composition of the GM is associated with neurodevelopment of the child. PAHs seem to change the relative abundance of some taxa (some deleted and some recruited) to counteract the negative effects of the PAHs.

Development and validation of a photographic atlas of food portions for accurate quantification of dietary intakes in China.

BACKGROUND: Accurate estimation of food portion sizes remains an important challenge in dietary data collection. The present study aimed to develop a food atlas with adequate visual reference to improve the accuracy of dietary surveys in China. METHODS: A food atlas for dietary surveys in China was developed using three visual reference systems, namely, regularly placed food portions, the two-dimensional background coordinates and common objects known in daily life. The atlas was validated by estimating a meal before and after using the food atlas, and differences in weight estimation were compared using a paired t-test. In total, 50 college students participated in the study. RESULTS: After determination of food varieties; design of the food display; purchase, processing, cooking and weighing of food; photographing food; post-image processing and data processing, a total of 799 pictures of 303 types of food and two types of tableware were produced. The mean value of food weight estimated with the atlas was closer to the actual weight, and the variation range of these values was smaller and more stable than that estimated without the atlas. The differences estimated before and after using the atlas for all foods were significant (P < 0.05). Comparing the differences in weight before using the atlas, the error ranges of food samples were reduced. CONCLUSIONS: A food atlas has been developed for a retrospective dietary survey in China, which can be used to enable a better understanding of nutritional adequacy in the Chinese population.

A novel Nogo-66 receptor antagonist peptide promotes neurite regeneration in vitro.

The Nogo-66 receptor (NgR1), a receptor for Nogo-A, contributes to the inhibition of axonal regeneration in the adult central nervous system after traumatic injuries. Thus, NgR1 has been considered a critical target in axon regeneration therapy. Here, we identified a specific NgR1 antagonist peptide (HIYTALV, named NAP2) which promotes neurite regeneration in vitro from a phage display heptapeptide library. NAP2 was co-localized with NgR1 on the surface of PC12 cells and cerebellar granule cells (CGCs) by immunofluorescence assay. Horseradish peroxidase (HRP)-streptavidin-biotin assay further showed that NAP2 binds to NgR1 and the dissociation constant (Kd) was 0.45 µM Functional analyses indicated that NAP2 could reduce the inhibitory effects of Nogo-66 on neurite outgrowth in differentiated PC12 cells and CGCs by blocking the Nogo-66-induced activation of Rho-associated coiled coil-containing protein kinase (ROCK), collapsin response mediator protein 2 (CRMP2) and myosin light chain (MLC). Taken together, the small molecule NgR1 antagonist peptide NAP2 (MW: 815.98Da) has a potential ability in crossing blood brain barrier and will be a promising therapeutic agent for the treatment of spinal cord injury and neurodegenerative diseases.

Recombinant Nogo-66 via soluble expression with SUMO fusion in Escherichia coli inhibits neurite outgrowth in vitro.

Nogo-66, a hydrophilic loop of 66 amino acids flank two hydrophobic domains of the Nogo-A C terminus, interacts with the Nogo-66 receptor (NgR) to exert numerous functions in the central nervous system (CNS). Nogo-66 has important roles in aspects of neuronal development, including cell migration, axon guidance, fasciculation, and dendritic branching, and in aspects of CNS plasticity, including oligodendrocyte differentiation and myelination. Here, the small ubiquitin-related modifier (SUMO) was fused to the target gene, Nogo-66, and the construct was expressed in Escherichia coli (E. coli). Under the optimal fermentation conditions, the soluble expression level of the fusion protein was 33 % of the total supernatant protein. After cleaving the fusion proteins with SUMO protease and purifying them by Ni-NTA affinity chromatography, the yield and purity of recombinant Nogo-66 obtained by 10-L scale fermentation were 23 ± 1.5 mg/L and greater than 93 %, respectively. The authenticity of the recombinant Nogo-66 was confirmed by an electrospray ionization-mass spectrometry analysis. The functional analyses indicated that the recombinant Nogo-66 was capable of binding the NgR specifically. The immunofluorescence results showed that the recombinant Nogo-66 could significantly inhibit neurite outgrowth of rat pheochromocytoma (PC12) cells stimulated by nerve growth factor and cerebellar granule cells (CGCs). Furthermore, Nogo-66 inhibited neurite outgrowth by increasing the level of phosphorylated Rho-associated coiled-coil-containing protein kinase 2 (ROCK2), collapsin response mediator protein 2 (CRMP2), and myosin light chain (MLC). This study provided a feasible and convenient production method for generating sufficient recombinant Nogo-66 for experimental and clinical applications.

Relevance of genetic causes and environmental adaptation of Cronobacter spp. isolated from infant and follow-up formula production factories and retailed products in China: A 7-year period of continuous surveillance based on genome-wide analysis.

The possible contamination routes, environmental adaptation, and genetic basis of Cronobacter spp. in infant and follow-up formula production factories and retailed products in mainland China have been determined by laboratory studies and whole-genome comparative analysis in a 7-year nationwide continuous surveillance spanning from 2012 to 2018. The 2-year continuous multicenter surveillance of the production process (conducted in 2013 and 2014) revealed that the source of Cronobacter spp. in the dry-blending process was the raw dry ingredients and manufacturing environment (particularly in the vibro sieve and vacuum cleaner), while in the combined process, the main contamination source was identified as the packing room. It is important to note that, according to the contamination control knowledge obtained from the production process surveillance, the contamination rate of retail powdered infant formula (PIF) and follow-up formula (FUF) products in China decreased significantly from 2016 onward, after improving the hygiene management practices in factories. The prevalence of Cronobacter spp. in retailed PIF and FUF in China in 2018 was dramatically reduced from 1.55 % (61/3925, in 2012) to an average as low as 0.17 % (13/7655 in 2018). Phenotype determination and genomic analysis were performed on a total of 90 Cronobacter spp. isolates obtained from the surveillance. Of the 90 isolates, only two showed resistance to either cefazolin or cefoxitin. The multilocus sequence typing results revealed that C. sakazakii sequence type 1 (ST1), ST37, and C. malonaticus ST7 were the dominant sequence types (STs) collected from the production factories, while C. sakazakii ST1, ST4, ST64, and ST8 were the main STs detected in the retailed PIF and FUF nationwide. One C. sakazakii ST4 isolate (1.1 %, 1/90) had strong biofilm-forming ability and 13 isolates (14.4 %, 13/90) had weak biofilm-forming ability. Genomic analysis revealed that Cronobacter spp. have a relatively stable core-genome and an increasing pan-genome size. Plasmid IncFIB (pCTU3) was prevalent in this genus and some contained 14 antibacterial biocide- and metal-resistance genes (BMRGs) including copper, silver, and arsenic resistant genes. Plasmid IncN_1 was predicted to contain 6 ARGs. This is the first time that a multi-drug resistance IncN_1 type plasmid has been reported in Cronobacter spp. Genomic variations with respect to BMRGs, virulence genes, antimicrobial resistance genes (ARGs), and genes involved in biofilm formation were observed among strains of this genus. There were apparent differences in copies of bcsG and flgJ between the biofilm-forming group and non-biofilm-forming group, indicating that these two genes play key roles in biofilm formation. The findings of this study have improved our understanding of the contamination characteristics and genetic basis of Cronobacter spp. in PIF and FUF and their production environment in China and provide important guidance to reduce contamination with this pathogen during the production of PIF and FUF.

[Determination of 24 minerals in human milk by inductively coupled plasma mass spectrometry with microwave digestion].

OBJECTIVE: To determine the levels of 24 minerals in human milk by inductively coupled plasma mass spectrometry with microwave digestion. METHODS: The samples were digested by microwave. The contents of minerals were determined by inductively coupled plasma mass spectrometry. The standard reference minerals of 1849a and 1568a from National Institute of Science and Technology were used for quality control. The accuracy and reproduability for this method were evaluated with mix standards and 1849a and 1568a standard reference materials. RESULTS: The ranges of the levels of sodium, magnesium, phosphorus, potassium, calcium, aluminum, chromium, arsenic, selenium, iron, zinc, manganese, copper, molybdenum, vanadium, cobalt, nickel, gallium, cadmium, silver, strontium, cesium, barium, lead in human milk was 34.97-415.83 mg/kg, 19.00-39.52 mg/kg, 102.13-274.53 mg/kg, 351.19-713.99 mg/kg, 180.08-349.64 mg/kg, 0.06-0.44 mg/kg, 0.9-7.37 microg/kg, 0.92-2.72 microg/kg, 0.20-21.15 microg/kg, 0.10-0.70 mg/kg, 0.56-3.25 mg/kg, 3.00-16.12 micro.g/kg, 62.16-591.69 microg/kg, 0.02-6.91 microg/kg, 5.99-13.70 microg/kg, 0.07-2.11 microg/kg, 0.77-209.26 microg/kg, 0.005-0.28 microg/kg, 0.02-0.23 microg/kg, 0.02-0.71 microg/kg, 36.89-132.26 microg/kg, 0.01-4.72 microg/kg, 0.83-28.16 microg/kg, 2.5-5.3 microg/kg, respectively. The levels of minerals in human milk in present study were consisted with other similar studies. CONCLUSION: The experiment examined the levels of minerals in human milk satisfactorily. The method has high accuracy and good reproducibility, which could be used for understanding the levels of minerals in human milk.

A single-tube-braided stent for various airway structures.

Background: Airway stent has been widely used in airway procedures. However, the metallic and silicone tubular stents are not customized designed for individual patients and cannot adapt to complicated obstruction structures. Other customized stents could not adapt to complex airway structures with easy and standardized manufacturing methods. Object: This study aimed to design a series of novel stents with different shapes which can adapt to various airway structures, such as the "Y" shape structure at the tracheal carina, and to propose a standardized fabrication method to manufacture these customized stents in the same way. Methods: We proposed a design strategy for the stents with different shapes and introduced a braiding method to prototype six types of single-tube-braided stents. Theoretical model was established to investigate the radial stiffness of the stents and deformation upon compression. We also characterized their mechanical properties by conducting compression tests and water tank tests. Finally, a series of benchtop experiments and ex vivo experiments were conducted to evaluate the functions of the stents. Results: The theoretical model predicted similar results to the experimental results, and the proposed stents could bear a compression force of 5.79N. The results of water tank tests showed the stent was still functioning even if suffering from continuous water pressure at body temperature for a period of 30 days. The phantoms and ex-vivo experiments demonstrated that the proposed stents adapt well to different airway structures. Conclusion: Our study offers a new perspective on the design of customized, adaptive, and easy-to-fabricate stents for airway stents which could meet the requirements of various airway illnesses.

Retinal safety and toxicity study of artesunate in vitro and in vivo.

Background: Artesunate (ART), a member of the artemisinin family, possesses multi-properties, including anti-inflammation, anti-oxidation, and anti-tumor. ART was recently reported to show anti-neovascularization effect on the cornea, iris, and retina. Compared to the expensive anti-VEGF treatment, this versatile, economical treatment option is attractive in the ophthalmic field. The safety and toxicity profile of ART intravitreal application are in utmost need. Methods: In this study, immortalized microglial (IMG) cells were treated with ART to determine the safe concentrations without inducing overt inflammatory reactions. Reverse transcription-polymerase chain reaction analysis was used to detect the cytokine expressions in IMG cells in response to ART stimulation. Various doses of ART were intravitreally injected into the right eyes of C57BL/6 mice. Retinal function was tested by electroretinogram, and retinal ganglion cell (RGC) survival was evaluated by counting Brn3a stained cells in flat-mounted retinas at 7 days after ART injection. Results: ART below 5µM was safe for IMG cells in vitro. Both 2.5 and 5 â€‹µM ART treatment increased IL-10 gene expression in IMG cells while not changing IL-1ß, IL-6, TNF-α, and Arg-1. In the in vivo study, intravitreal injection of ART below 100 â€‹µM did not cause deterioration in the retinal function and RGC survival of the mouse eyes, while 1 â€‹mM ART treatment significantly attenuated both the scotopic and photopic b-wave amplitudes and impaired RGC survival. In addition, treatment with ART of 25, 50, and 100 â€‹µM significantly decreased TNF-α gene expression while ART of 100 â€‹µM significantly increased IL-10 in the mouse retina. Conclusions: Intravitreal injection of 100 â€‹µM ART could downregulate TNF-α while upregulate IL-10 in the mouse retina without causing retinal functional deterioration and RGC loss. ART might be used as anti-inflammatory agent for retinal disorders.

[Effect of different dietary protein source and protein level on serum lipids profile in rats].

OBJECTIVE: The aim of this study was to evaluate the effect of dietary protein source and protein level on serum lipids in male rats. METHODS: Wistar weaning male rats were assigned to four groups (15 rats in each group) according to their original body weight. The effects of two kinds of dietary protein with two different levels, including low cow milk (LM, 9%), high cow milk (HM, 18%), low soybean and egg white (LS, 9%), and high soybean and egg white (HS, 18%) diets, were observed. Each group was provided with one of four diets for 20 weeks. Serum lipids were tested and the ratio of lipid were calculated. RESULTS: Serum TC and HDL-C were the highest and TC/HDL-C was the lowest in HM group; serum TG in HS group was the lowest. The ratio of TG/HDL-C in HS and HM group was lower than LS and LM group. Compared with LM and HM groups, serum LDL-C and LDL-C/HDL-C was lower in LS and HS group. CONCLUSION: Long-term intake of protein from soybean and egg white, serum TG level may be significantly lower, which may reduce the risk of atherosclerosis. There was a trend of rising serum cholesterol level in rats fed with protein from cow milk for a long time.

[Serum retinol and carotenoid of rural infants and young children in Linyi of Shangdong Province and analysis on their related influencing dietary factors].

OBJECTIVE: The study was carried out to determine serum retinol and carotenoid of infants and young children in rural areas, and to explore their related dietary factors. METHODS: A total of 254 rural healthy infants and young children aged 6-24 month-old were recruited from a program for health examination and feeding survey conducted in villages in Meibu of Linyi of Shandong Province by cluster sampling method. Serum retinol, beta-carotene, alpha-carotene, beta-cryptoxanthin and lutein + zeaxanthin were detected with HPLC. The frequency of food intake of babies during the past month was inquired from their mothers or baby-sitters. The relationship between serum retinol and carotenoid level with some factors related to feeding pattern was analyzed. RESULTS: The average serum retinol was (0.96 +/- 0.55) micromol/L with little variation by age (P > 0.05). The prevalence of serum vitamin A deficiency and marginal deficiency were 40.6% and 32.6%. The average serum beta-carotene, alpha-carotene, beta-cryptoxanthin and lutein + zeaxanthin were (0.056 +/- 0.088) micromol/L, (3.3 +/- 12.1) nmol/L, (27.0 +/- 45.2) nmol/L and (0.22 +/- 0.22) micromol/L, respectively, and no significant difference between age groups on serum beta-carotene, alpha-carotene and beta-cryptoxanthin (all were P > 0.05) except lutein + zeaxanthin (P < 0.05). Breast feeding and formula feeding were significant dietary factors influencing serum retinol and carotenoids levels. The frequency of breast-feeding was correlated significantly with serum beta-carotene (P < 0.05). Serum retinol was correlated positively with carotenoids and among carotenoids with each other (all were P < 0.001). CONCLUSION: Vitamin A deficiency and marginal deficiency were prevalent in the investigated infants and young children. Serum carotenoid was little variation with age, but was different significantly with dietary patterns fed by breast milk, formula, or fruits and vegetables.

Lycium barbarum extract promotes M2 polarization and reduces oligomeric amyloid-ß-induced inflammatory reactions in microglial cells.

Lycium barbarum (LB) is a traditional Chinese medicine that has been demonstrated to exhibit a wide variety of biological functions, such as antioxidation, neuroprotection, and immune modulation. One of the main mechanisms of Alzheimer's disease is that microglia activated by amyloid beta (Aß) transform from the resting state to an M1 state and release pro-inflammatory cytokines to the surrounding environment. In the present study, immortalized microglial cells were pretreated with L. barbarum extract for 1 hour and then treated with oligomeric Aß for 23 hours. The results showed that LB extract significantly increased the survival of oligomeric Aß-induced microglial cells, downregulated the expression of M1 pro-inflammatory markers (inducible nitric oxide synthase, tumor necrosis factor α, interleukin-6, and interleukin-1ß), and upregulated the expression of M2 anti-inflammatory markers (arginase-1, chitinase-like protein 3, and interleukin-4). LB extract also inhibited the oligomeric Aß-induced secretion of tumor necrosis factor α, interleukin-6, and interleukin-1ß in microglial cells. The results of in vitro cytological experiments suggest that, in microglial cells, LB extract can inhibit oligomeric Aß-induced M1 polarization and concomitant inflammatory reactions, and promote M2 polarization.

[Interventional effect of vitamin A supplementation on re-vaccination to hepatitis B virus among rural infants and young children in China].

OBJECTIVE: The objective of this study was to observe the interventional effect of cod liver oil supplementation on re-vaccination to hepatitis B virus (HBV) among infants and young children. METHODS: All 7-36 months old infants and young children, who had been vaccinated with obligatory HBV vaccines routinely by the national technical and administrative procedures for HBV vaccination on children of China, were convened among villages in Linyi, Shandong province, from October 2008 to March 2009. After detection of serum anti-HBV, one hundred children with lower serum anti-HBV were picked out for the randomized, double blinded, placebo controlled vitamin A supplementation study. The children in the intervention group (50 subjects) took 0.5 g condensed cod liver oil (containing 25 000 IU vitamin A and 2500 IU vitamin D(2)) every 15 days for six times. The children in the control group (50 subjects) were given corn oil with same volume. All children were re-vaccinated at the 30th and the 60th day of the experiment. The serum samples were collected from each child at the 90th day of the experiment. Retinol concentration in serum samples was analyzed with HPLC method before and after the intervention. The levels of serum anti-HBs were detected by the electro-chemi-luminescence immunoassay (ECLIA). RESULTS: Total 74 children finished the supplemental experiment and blood collection, 37 subjects in each group, respectively. After intervention, the serum retinol level in the experimental and control group were (404.1 ± 123.1) and (240.8 ± 92.8) µg/L (t = 6.441, P < 0.01), respectively. The serum anti-HBs levels in the experimental and control group were (2737.2 ± 2492.6) and (1199.7 ± 2141.6) U/L (t = 2.846, P < 0.01), respectively. The rate of weak or no-answer case in experimental and control groups was 0.00% (0/37) and 10.81% (4/37) (χ(2) = 4.229, P = 0.040), respectively. CONCLUSION: The results showed that vitamin A supplementation might enhance the re-vaccination reaction against HB vaccine in infants and young children.

Electrical stimulation at nanoscale topography boosts neural stem cell neurogenesis through the enhancement of autophagy signaling.

Neural stem cells (NSCs) transplantation at the injury site of central nerve system (CNS) makes it possible for neuroregeneration. Long-term cell survival and low proliferation, differentiation, and migration rates of NSCs-graft have been the most challenging aspect on NSCs application. New multichannel electrical stimulation (ES) device was designed to enhance neural stem cells (NSCs) differentiation into mature neurons. Compared to controls, ES at nanoscale topography enhanced the expression of mature neuronal marker, growth of the neurites, concentration of BDNF and electrophysiological activity. RNA sequencing analysis validated that ES promoted NSC-derived neuronal differentiation through enhancing autophagy signaling. Emerging evidences showed that insufficient or excessive autophagy contributes to neurite degeneration. Excessive ES current were able to enhance neuronal autophagy, the neuronal cells showed poor viability, reduced neurite outgrowth and electrophysiological activity. Well-controlled autophagy not only protects against neurodegeneration, but also regulates neurogenesis. Current NSC treatment protocol efficiently enhanced NSC differentiation, maturation and survival through combination of proper ES condition followed by balance of autophagy level in the cell culture system. The successful rate of such protreated NSC at injured CNS site should be significantly improved after transplantation.

Electrical stimulation affects neural stem cell fate and function in vitro.

Electrical stimulation (ES) has been applied in cell culture system to enhance neural stem cell (NSC) proliferation, neuronal differentiation, migration, and integration. According to the mechanism of its function, ES can be classified into induced electrical (EFs) and electromagnetic fields (EMFs). EFs guide axonal growth and induce directional cell migration, whereas EMFs promote neurogenesis and facilitates NSCs to differentiate into functional neurons. Conductive nanomaterials have been used as functional scaffolds to provide mechanical support and biophysical cues in guiding neural cell growth and differentiation and building complex neural tissue patterns. Nanomaterials may have a combined effect of topographical and electrical cues on NSC migration and differentiation. Electrical cues may promote NSC neurogenesis via specific ion channel activation, such as SCN1α and CACNA1C. To accelerate the future application of ES in preclinical research, we summarized the specific setting, such as current frequency, intensity, and stimulation duration used in various ES devices, as well as the nanomaterials involved, in this review with the possible mechanisms elucidated. This review can be used as a checklist for ES work in stem cell research to enhance the translational process of NSCs in clinical application.

A novel method of neural differentiation of PC12 cells by using Opti-MEM as a basic induction medium.

The PC12 cell line is a classical neuronal cell model due to its ability to acquire the sympathetic neurons features when deal with nerve growth factor (NGF). In the present study, the authors used a variety of different methods to induce PC12 cells, such as Opti-MEM medium containing different concentrations of fetal bovine serum (FBS) and horse serum compared with RPMI-1640 medium, and then observed the neurite length, differentiation, adhesion, cell proliferation and action potential, as well as the protein levels of axonal growth-associated protein 43 (GAP-43) and synaptic protein synapsin-1, among other differences. Compared with the conventional RPMI-1640 medium induction method, the new approach significantly improved the neurite length of induced cells (2.7 times longer), differentiation rate (30% increase), adhesion rate (21% increase) and expression of GAP-43 and synapsin-1 (three times), as well as reduced cell proliferation. The morphology of induced cells in Opti-MEM medium containing 0.5% FBS was more like that of neurons. Additionally, induced cells were also able to motivate the action potential after treatment for 6 days. Therefore, the research provided a novel, improved induction method of neural differentiation of PC12 cells using Opti-MEM medium containing 0.5% FBS, resulting in a better neuronal model cell line that can be widely used in neurobiology and neuropharmacology research.

Role of amyloid ß protein receptors in mediating synaptic plasticity.

There are few diseases in modern biomedicine that have garnered as much scientific interest and public concern as Alzheimer's disease (AD). The amyloid hypothesis has become the dominant model of AD pathogenesis; however, the details of the hypothesis are changing over time. Recently, given the increasing recognition, subtle effects of amyloid ß protein (Aß) on synaptic efficacy may be critical to AD progression. Synaptic plasticity is the important neurochemical foundation of learning and memory. Recent studies have identified that soluble Aß oligomers combine with certain receptors to impair synaptic plasticity in AD, which advanced the amyloid hypothesis. The aim of the present review was to summarize the role of Aß-relevant receptors in regulating synaptic plasticity and their downstream signaling cascades, which may provide novel insights into the understanding of the pathogenesis of AD and the development of therapeutic strategies to slow down the progression of AD-associated memory decline in the early stages.

Synthesis, characterization and anti-cancer activity of Pluronic F68-curcumin conjugate micelles.

Curcumin (CUR), a nontoxic polyphenol derived from the rhizome of turmeric (Curcuma longa), has been recognized as an anti-cancer and chemo-preventative agent. However, its clinical application for cancer treatment has been greatly limited due to its poor water-solubility and low bioavailability. To tackle this problem, Pluronic F68-CUR (F68-CUR) conjugate micelles, which are amphiphilic copolymers, were designed and synthesized in this study. These highly stable micelles with CUR concentrated in the core were formulated using the solvent evaporation method and were confirmed by Fourier transform infrared spectroscopy and nuclear magnetic resonance. Physicochemical characterization of F68-CUR conjugate micelles revealed that high drug loading content (DL%; 0.248 mg CUR/1 mg F68) was achieved, and the average particle size of micelles was 115.2 ± 3.0 nm. Compared with free CUR, a significantly higher cytotoxicity against human breast cancer cell line MDA-MB-231 was observed in F68-CUR conjugate micelles. The IC50 value of F68-CUR conjugate micelles was 1.95-fold lower than that of free CUR, indicating that the anti-cancer activity of CUR was significantly improved in the micelles. Furthermore, apoptotic studies demonstrated that F68-CUR conjugate micelles induced more cell apoptosis than that of free CUR. Taken together, these results demonstrate that F68-CUR conjugate micelles are promising to improve the clinical effectiveness of CUR in cancer treatment.

Function of Nogo-A/Nogo-A receptor in Alzheimer's disease.

Nogo-A is a protein inhibiting axonal regeneration, which is considered a major obstacle to nerve regeneration after injury in mammals. Rapid progress has been achieved in new physiopathological function of Nogo-A in Alzheimer's disease in the past decade. Recent research shows that through binding to Nogo-A receptor, Nogo-A plays an important role in Alzheimer's disease (AD) pathogenesis. Particularly, Nogo-A/Nogo-A receptors modulate the generation of amyloid ß-protein (Aß), which is thought to be a major cause of AD. This review describes the recent development of Nogo-A, Nogo-A receptor, and downstream signaling involved in AD and pharmacological basis of therapeutic drugs. We concluded the Nogo-A/Nogo-A receptor provide new insight into potential mechanisms and promising therapy strategies in AD.