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The expending of elderly population worldwide has resulted in a dramatic rise in the incidence of chronic diseases such as Alzheimer's disease (AD). Inadequate understanding of the mechanisms underlying AD has hampered the development of efficient tools for definitive diagnosis and curative interventions. Previous studies have attempted to discover reliable biomarkers of AD, but these biomarkers can only be measured through invasive (neuropathological markers in cerebrospinal fluid) or expensive (positron emission tomography scanning or magnetic resonance imaging) techniques. Metabolomics is a high-throughput technology that can detect and catalog large numbers of small metabolites and may be a useful tool for characterization of AD and identification of biomarkers. In this study, we used ultra-performance liquid chromatography-mass spectrometry based untargeted metabolomics to measure the concentrations of plasma metabolites in a cohort of subjects with AD (n=44) and cognitively normal controls (Ctrl, n=94). The AD group showed marked reductions in levels of polyunsaturated fatty acids, acyl-carnitines, degradation products of tryptophan, and elevated levels of bile acids compared to the Ctrl group. We then validated the results using an independent cohort that included subjects with AD (n=30), mild cognitive impairment (MCI, n=13), healthy controls (n=43), and non-AD neurological disease controls (NDC, n=31). We identified five metabolites comprising cholic acid, chenodeoxycholic acid, allocholic acid, indolelactic acid, and tryptophan that were able to distinguish patients with AD from both Ctrl and NDC with satisfactory sensitivity and specificity. The concentrations of these metabolites were significantly correlated with disease severity. Our results also suggested that altered bile acid profiles in AD and MCI might indicate early risk for the development of AD. These findings may allow for development of new approaches for diagnosis of AD and may provide novel insights into AD pathogenesis.

Respiratory syncytial virus (RSV) can cause lower respiratory tract infections, such as bronchiolitis in infants. In China, traditional asthma-relieving medicine has numerous clinical applications in the treatment of RSV infections. However, due to the complexity of the traditional Chinese medicine system, its therapeutic mechanism and main pharmacological components remain unclear. Metabolomics can be used to analyze the efficacy of traditional Chinese medicine to provide modern scientific evidence for such treatments. In this study, an animal model experiment was performed with seven groups of three-week-old rats. The model group and five intervention groups were inoculated nasally with RSV for three consecutive days, and the normal group was treated with the same amount of saline for three consecutive days under the same conditions. In parallel, the five intervention groups were treated separately with the following via intragastric administration for seven consecutive days: asthma-relieving traditional Chinese medicine decoction, its three constituent agents (ascending (xuan) therapy, descending (jiang) therapy, pyretic clearing (qing) therapy), and ribavirin. Both normal group and RSV model group were administered with normal saline via intragastric administration as controls for seven consecutive days. The fundus plasma of rats in each group was collected on day 0, day 3, and day 7. Liquid chromatography-mass spectrometry-based untargeted metabolomics analysis was performed to investigate the changes in the metabolome after RSV infection, the effects of the asthma-relieving decoction on the regulation of metabolites related to RSV infection, and the primary source of efficacy. The detected metabolite ions were corrected using internal standards. Multivariate analysis of ions with an RSD value of less than 30% in quality control (QC) samples was used to construct principal component analysis models to monitor the overall metabolic changes of each group. The results showed that, during RSV infection and treatment, the asthma-relieving decoction and the positive control ribavirin had similar effects on the overall metabolic regulation of RSV-infected rats. Among the three asthma-relieving decoction constituent agents, the ascending (xuan) therapy agents which was composed of ephedra and ginkgo had a closer metabolic regulation effect with asthma-relieving decoction, and might be the main source of pharmacological efficacy. Based on the retention time, m/z value and tandem mass spectra in the database established by our laboratory, a total of 150 metabolites were identified. Paired t-tests were performed using data of the identified metabolites before and after RSV infection in each group, and it was found that 83 metabolite levels significantly changed after RSV infection, indicating that RSV infection could lead to disorders of multiple metabolic pathways in rats. The altered pathways included aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, primary bile acid biosynthesis, phenylalanine metabolism and sphingomyelin metabolism. On the third day, the asthma-relieving decoction had regulatory effects on several metabolites such as bile acids, amino acids, organic acids, lipids, etc. Among the three asthma-relieving decoction constituent agents, the ascending (xuan) therapy agents had more similar effects on the regulation of metabolites with the asthma-relieving decoction. On the other hand, the descending (jiang) therapy agents and pyretic clearing (qing) therapy agents down-regulated the abnormal increase in acylcarnitine caused by the RSV infection. Additionally, both asthma-relieving decoction and its constituent agents could maintain the stability of the immune system and metabolism of the intestinal flora in rats. This study used metabolomics to evaluate the efficacy of an asthma-relieving decoction and demonstrate the metabolites and the corresponding changes after asthma-relieving decoction-based treatment. It provides theoretical support for research on the therapeutic mechanism and active ingredients of asthma-relieving decoction.

Chalcones (1,3-diaryl-2-propen-1-ones) are precursors for flavonoids and isoflavonoids, which are common simple chemical scaffolds found in many naturally occurring compounds. Many chalcone derivatives were also prepared due to their convenient synthesis. Chalcones as weandhetic analogues have attracted much interest due to their broad biological activities with clinical potentials against various diseases, particularly for antitumor activity. The chalcone family has demonstrated potential in vitro and in vivo activity against cancers via multiple mechanisms, including cell cycle disruption, autophagy regulation, apoptosis induction, and immunomodulatory and inflammatory mediators. It represents a promising strategy to develop chalcones as novel anticancer agents. In addition, the combination of chalcones and other therapies is expected to be an effective way to improve anticancer therapeutic efficacy. However, despite the encouraging results for their response to cancers observed in clinical studies, a full description of toxicity is required for their clinical use as safe drugs for the treatment of cancer. In this review, we will summarize the recent advances of the chalcone family as potential anticancer agents and the mechanisms of action. Besides, future applications and scope of the chalcone family toward the treatment and prevention of cancer are brought out.

Large-scale population screenings are not feasible by applying laborious oral glucose tolerance tests, but using fasting blood glucose (FPG) and glycated hemoglobin (HbA1c), a considerable number of diagnoses are missed. A novel marker is urgently needed to improve the diagnostic accuracy of broad-scale diabetes screening in easy-to-collect blood samples. In this study, by applying a novel knowledge-based, multistage discovery and validation strategy, we scaled down from 108 diabetes-associated metabolites to a diagnostic metabolite triplet (Met-T), namely hexose, 2-hydroxybutyric/2-hydroxyisobutyric acid, and phenylalanine. Met-T showed in two independent cohorts, each comprising healthy controls, prediabetic, and diabetic individuals, distinctly higher diagnostic sensitivities for diabetes screening than FPG alone (>79.6 vs 32% using fasting plasma glucose down to

Soil nitrification, mediated mainly by ammonia oxidizing archaea (AOA) and bacteria (AOB), converts ammonium (NH4 +) to nitrite (NO2 -) and thence nitrate (NO3 -). To better understand ecological differences between AOA and AOB, we investigated the nitrification kinetics of AOA and AOB under eight replicated cropped and unmanaged ecosystems (including two fertilized natural systems) along a long-term management intensity gradient in the upper U.S. Midwest. For five of eight ecosystems, AOB but not AOA exhibited Haldane kinetics (inhibited by high NH4 + additions), especially in perennial and successional systems. In contrast, AOA predominantly exhibited Michaelis-Menten kinetics, suggesting greater resistance to high nitrogen inputs than AOB. These responses suggest the potential for NH4 +-induced niche differentiation between AOA and AOB. Additionally, long-term fertilization significantly enhanced maximum nitrification rates (Vmax ) in the early successional systems for both AOA and AOB, but not in the deciduous forest systems. This was likely due to pH suppression of nitrification in the acidic forest soils, corroborated by a positive correlation of Vmax with soil pH but not with amoA gene abundance. Results also demonstrated that soil nitrification potentials were relatively stable, as there were no seasonal differences. Overall, results suggest that (1) NH4 + inhibition of AOB but not AOA could be another factor contributing to niche differentiation between AOA and AOB in soil, and (2) nitrification by both AOA and AOB can be significantly promoted by long-term nitrogen inputs.

Autotrophic nitrification is mediated by ammonia oxidizing bacteria (AOB) or ammonia oxidizing archaea (AOA) and nitrite oxidizing bacteria (NOB). Mounting studies have examined the impact of nitrogen (N) fertilization on the dynamic and diversity of AOA and AOB, while we have limited information on the response of the activity, abundance, and diversity of NOB to N fertilization. We investigated the influence of organic and inorganic N fertilizers on soil NOB in silage corn field plots that received contrasting nitrogen (N) treatments: control (no additional N), ammonium sulfate (AS 100 and 200 kg N ha−1), and compost (200 kg N ha−1). Nitrifying community was examined using a universal marker (16S rRNA gene), functional gene markers (AOB amoA and Nitrospira nxrB), and metagenomics. The overall nitrifying community was not altered after the first fertilization but was significantly shifted by 4-year repeated application of ammonium fertilizers. Nitrospira were the dominant NOB (>99.7%) in our agricultural soil. Both community compositions of AOB and Nitrospira were significantly changed by ammonium fertilizers but not by compost after 4 years of repeated applications. All nitrifiers, including comammox, were recovered in soil metagenomes based on a gene-targeted assembly, but their sequence counts were very low. Although N treatment did not affect the abundance of Nitrospira nxrB determined by real-time quantitative PCR, ammonium fertilizers significantly promoted rates of potential nitrite oxidation determined at 0.15 mM nitrite in soil slurries. Understanding the response of both ammonia oxidizers and nitrite oxidizers to N fertilization may initiate or improve strategies for mitigating potential environmental impacts of nitrate production in agricultural ecosystems.

Unclarified molecular mechanism and lack of practical diagnosis biomarkers hinder the effective treatment of non-small-cell lung cancer. Herein, we performed liquid chromatography-mass spectrometry-based nontargeted metabolomics analysis in 131 patients with their lung tissue pairs to study the metabolic characteristics and disordered metabolic pathways in lung tumor. A total of 339 metabolites were identified in metabolic profiling. Also, 241 differential metabolites were found between lung carcinoma tissues (LCTs) and paired distal noncancerous tissues; amino acids, purine metabolites, fatty acids, phospholipids, and most of lysophospholipids significantly increased in LCTs, while 3-phosphoglyceric acid, phosphoenolpyruvate, 6-phosphogluconate, and citrate decreased. Additionally, pathway enrichment analysis revealed that energy, purine, amino acid, lipid, and glutathione metabolism are markedly disturbed in lung cancer (LCa). Using binary logistic regression, we further defined candidate biomarkers for different subtypes of lung tumor. Xanthine and PC 35:2 were selected as combinational biomarkers for distinguishing benign from malignant lung tumors with a 0.886 area under curve (AUC) value, and creatine, myoinositol and LPE 16:0 were defined as combinational biomarkers for discriminating adenocarcinoma from squamous cell lung carcinoma with a 0.934 AUC value. Overall, metabolic characterization and pathway disturbance demonstrated apparent metabolic reprogramming in LCa. The defined candidate metabolite marker panels are useful for subtyping of lung tumors to assist clinical diagnosis.

Autophagy is a mechanism that enables cells to maintain cellular homeostasis by removing damaged materials and mobilizing energy reserves in conditions of starvation. Although nutrient availability strongly impacts the process of autophagy, the specific metabolites that regulate autophagic responses have not yet been determined. Recent results indicate that S‐adenosylmethionine (SAM) represents a critical inhibitor of methionine starvation–induced autophagy. SAM is primarily involved in four key metabolic pathways: transmethylation, transsulphuration, polyamine synthesis and 5′‐deoxyadenosyl 5′‐radical–mediated biochemical transformations. SAM is the sole methyl group donor involved in the methylation of DNA, RNA and histones, modulating the autophagic process by mediating epigenetic effects. Moreover, the metabolites of SAM, such as homocysteine, glutathione, decarboxylated SAM and spermidine, also exert important influences on the regulation of autophagy. From our perspective, nuclear‐cytosolic SAM is a conserved metabolic inhibitor that connects cellular metabolic status and the regulation of autophagy. In the future, SAM might be a new target of autophagy regulators and be widely used in the treatment of various diseases., Working model for SAM‐mediated modulation of autophagy. SAM is an essential metabolite that acts as a high‐energy methyl donor for most methylation modifications of non‐histone, histone, DNA and RNA, which epigenetically affect autophagic flux. Moreover, SAM is the biosynthetic precursor for HCY and cysteine and other sulphur‐containing metabolites such as GSH. All of these roles significantly contribute to the modulation of autophagy. In addition, the SAM metabolite SPD has also been shown to be a physiological inducer of autophagy. Collectively, the metabolites of SAM and the key enzymes in SAM biosynthesis and metabolism influence the core autophagy machinery. S‐adenosylmethionine: SAM, homocysteine: HCY, glutathione: GSH, spermidine: SPD, AMP‐dependent protein kinase: AMPK, mechanistic target of rapamycin: mTOR, migration inhibitory factor: MIF, cystic fibrosis transmembrane conductance regulator: CFTR, mTOR complex 1: mTORC1, protein phosphatase 2A: PP2A, nitrogen permease regulating protein: NPR2P, ten‐eleven translocation methylcytosine dioxygenases: TET, N6‐methyladenosine RNA methylation, m6A RNA methylation

Soil extracellular enzymes play a significant role in the N mineralization process. However, few studies have documented the linkage between enzyme activity and the microbial community that performs the function. This study examined the effects of inorganic and organic N fertilization on soil microbial communities and their N mineralization functions over 4 years. Soils were collected from silage corn field plots with four contrasting N treatments: control (no additional N), ammonium sulfate (AS; 100 and 200 kg of N ha−1), and compost (200 kg of N ha−1). Illumina amplicon sequencing was used to comprehensively assess the overall bacterial community (16S rRNA genes), bacterial ureolytic community (ureC), and bacterial chitinolytic community (chiA). Selected genes involved in N mineralization were also examined using quantitative real-time PCR and metagenomics. Enzymes (and marker genes) included protease (npr and sub), chitinase (chiA), urease (ureC), and arginase (rocF). Compost significantly increased diversity of overall bacterial communities even after one application, while ammonium fertilizers had no influence on the overall bacterial communities over four seasons. Bacterial ureolytic and chitinolytic communities were significantly changed by N fertilization. Compost treatment strongly elevated soil enzyme activities after 4 years of repeated application. Functional gene abundances were not significantly affected by N treatments, and they were not correlated with corresponding enzyme activities. N mineralization genes were recovered from soil metagenomes based on a gene-targeted assembly. Understanding how the structure and function of soil microbial communities involved with N mineralization change in response to fertilization practices may indicate suitable agricultural management practices that improve ecosystem services while reducing negative environmental consequences. IMPORTANCE Agricultural N management practices influence the enzymatic activities involved in N mineralization. However, specific enzyme activities do not identify the microbial species directly involved in the measured process, leaving the link between the composition of the microbial community and the production of key enzymes poorly understood. In this study, the application of high-throughput sequencing, real-time PCR, and metagenomics shed light on how the abundance and diversity of microorganisms involved in N mineralization respond to N management. We suggest that N fertilization has significantly changed bacterial ureolytic and chitinolytic communities.

Soil ammonia-oxidizing bacteria and archaea (AOB and AOA) convert ammonium/ammonia to nitrite in the process of nitrification. However, the potentially differential responses of these AO to substrate and temperature and the effects of conventional and organic nitrogen management on these responses remains poorly understood. We determined the response of nitrification to ammonium substrate concentration and temperature using an AOB specific inhibitor to distinguish the contribution of AOB and AOA to nitrification. Soils were sampled from cornfield plots that had been treated for four years with contrasting nitrogen sources: control (no additional N), ammonium sulfate at two rates and compost. Nitrification potential and net rates were stimulated for one month after fertilization with ammonium sulfate compared to relatively lower and stable rates in control and compost treated soils. For soils that had been fertilized with ammonium sulfate, the proportion of nitrification mediated by AOB in slurry assays was over 90% at 1.0 mM but less than 50% at 0.01 mM. Kinetic analysis showed maximum nitrification activity (Vmax) for AOB ranged from 0.32 to 4.8 mmol N kg−1d−1 with a half saturation constant (Km) of 14–160 μM ammonium; parameters were higher for soils from ammonium sulfate treated plots. Vmax and Km for AOA averaged 0.24 mmol N kg−1d−1 and 4.28 μM ammonium with no effect of field treatment. The proportion of nitrification due to AOA was lowest at 5 °C, increased with temperature, and was near to 100% at 50 °C; optimum temperature was 41 °C for AOA versus 31 °C for AOB. Understanding the kinetic and temperature response of microbes responsible for nitrification may allow ecosystem models to include these populations as dynamic components driving nitrogen flux.

Agriculture is responsible for over half of the input of reactive nitrogen (N) to terrestrial systems; however improving N availability remains the primary management technique to increase crop yields in most regions. In the majority of agricultural soils, ammonium is rapidly converted to nitrate by nitrification, which increases the mobility of N through the soil matrix, strongly influencing N retention in the system. Decreasing nitrification through management is desirable to decrease N losses and increase N fertilizer use efficiency. We review the controlling factors on the rate and extent of nitrification in agricultural soils from temperate regions including substrate supply, environmental conditions, abundance and diversity of nitrifiers and plant and microbial interactions with nitrifiers. Approaches to the management of nitrification include those that control ammonium substrate availability and those that inhibit nitrifiers directly. Strategies for controlling ammonium substrate availability include timing of fertilization to coincide with rapid plant update, formulation of fertilizers for slow release or with inhibitors, keeping plant growing continuously to assimilate N, and increasing microbial N assimilation (immobilization). Another effective strategy is to inhibit nitrifiers directly with either synthetic or biological nitrification inhibitors. Commercial nitrification inhibitors are effective but their use is complicated by a changing climate and by organic management requirements. The interactions of the nitrifying organisms with plants or microbes producing biological nitrification inhibitors is a promising approach but just beginning to be critically examined. Climate smart agriculture will need to carefully consider optimized seasonal timing for these strategies to remain effective management tools.

In a Chinese prospective cohort, 500 patients with new‐onset type 2 diabetes (T2D) within 4.61 years and 500 matched healthy participants are selected as case and control groups, and randomized into discovery and validation sets to discover the metabolite changes before T2D onset and the related diabetogenic loci. A serum metabolomics analysis reveals that 81 metabolites changed significantly before T2D onset. Based on binary logistic regression, eight metabolites are defined as a biomarker panel for T2D prediction. Pipecolinic acid, carnitine C14:0, epinephrine and phosphatidylethanolamine 34:2 are first found associated with future T2D. The addition of the biomarker panel to the clinical markers (BMI, triglycerides, and fasting glucose) significantly improves the predictive ability in the discovery and validation sets, respectively. By associating metabolomics with genomics, a significant correlation (p, In a Chinese prospective cohort, 500 patients with new‐onset type 2 diabetes (T2D) within 4.61 years and 500 matched healthy participants are selected. A serum metabolomics analysis is performed and 81 metabolites are found to significantly change before T2D onset. The new biomarker panel helps to predict T2D. Gene FADS1, CHRM3, and WWOX are found to be associated with T2D‐related metabolites.

Diabetic retinopathy (DR) is the main cause of vision loss or blindness in working age adults worldwide. The lack of effective diagnostic biomarkers for DR leads to unsatisfactory curative treatments. To define potential metabolite biomarkers for DR diagnosis, a multiplatform‐based metabolomics study is performed. In this study, a total of 905 subjects with diabetes without DR (NDR) and with DR at different clinical stages are recruited. Multiplatform metabolomics methods are used to characterize the serum metabolic profiles and to screen and validate the DR biomarkers. Based on the criteria p, Multiplatform metabolomics methods are used to comprehensively investigate the association between the serum metabolic profiles and the onset and progression of diabetic retinopathy (DR) in a large Chinese population, and 12‐HETE and 2‐piperidone are identified as a highly effective marker panel for the detection of DR and early‐stage DR.

In the majority of agricultural soils, ammonium (NH4+) is rapidly converted to nitrate (NO3−) in the biological ammonia and nitrite oxidation processes known as nitrification. The often rate-limiting step of ammonia oxidation to nitrite is mediated by ammonia oxidizing bacteria (AOB) and ammonia oxidizing archaea (AOA). The response of AOA and AOB communities to organic and conventional nitrogen (N) fertilizers, and their relative contributions to the nitrification process were examined for an agricultural silage corn system using a randomized block design with 4 N treatments: control (no additional N), ammonium sulfate (AS) fertilizer at 100 and 200 kg N ha−1, and steer-waste compost (200 kg total N ha−1) over four seasons. DNA was extracted from the soil, and real-time PCR and 454-pyrosequencing were used to evaluate the quantity and diversity of the amoA gene which encodes subunit A of ammonia monooxygenase. Soil pH, nitrate pools, and nitrification potentials were influenced by ammonium and organic fertilizers after the first fertilization, while changes in AOB abundance and community structure were not apparent until after the second fertilization or later. The abundance of AOA was always greater than AOB but was unaffected by N treatments. In contrast, AOB abundance and community structure were changed significantly by ammonium fertilizers. Specific inhibitors of nitrification were used to evaluate the relative contribution of AOA and AOB to nitrification. We found that AOB dominantly contributed to potential nitrification activity determined at 1 mM ammonium in soil slurries and nitrification potential activity was higher in soils treated with ammonium fertilizers relative to control soils. However, AOA dominated gross nitrification activity in moist soils. Our result suggests that AOB activity and community are more responsive to ammonium fertilizers than AOA, but that in situ nitrification rate is controlled by ammonium availability in this agricultural soil. Understanding this response of AOA and AOB to N fertilizers may contribute to improving strategies for the management of nitrate production in agricultural soils.

Periodical changes of steroid hormones have a great impact on the homeostasis of the female. However, there are few studies concerning the metabolome changes during the cycle. To study the periodic metabolic changes, a female cohort was enrolled with time-series serum samples collected during a menstrual cycle. To meet the requirement of the large-scale sample analysis, a high throughput metabolomics method was established by using an efficient sample preparation on a 96 well filter plate and a rapid LC condition in 12 min, which reduces about 70% of the samples preprocessing time and 60% analysis time. Evaluation of metabolite coverage and separation performances reflected that the method was robust for the large-scale metabolomics study. Using this method, we found that 12.6% of total detected ions including lipids, amino acids, citric acid, and so on were significantly changed during a menstrual cycle. Some metabolites were found periodically changed, which is similar to hormones (estrone and progesterone) during the cycle. These results show the novel high throughput method can be applied in large-scale metabolomics studies.

Bacterial cellulose (BC) with a porous structure was prepared via a facile surfactant-assisted foaming method in azodicarbonamide (AC)-NaOH aqueous solution under mild condition. The time-saving and flexible procedure comprises immersing and foaming of BC membranes in AC solution, washing and subsequent freeze drying. The results showed that BC with the surfactant Tween 80 assisted foaming treatment had the homogeneous and interconnected spherical macroporous structure with the pore size up to 20 μm. Compared to native BC, its mesoporous surface area was increased from 56.87 m2/g to 169.86 m2/g, the porosity was increased from 28.3% to 90.8% and the maximum water adsorption was increased from 997% to 7611%.

A novel composites material consisting of calcium silicate deposited in bacterial cellulose membrane was synthesized by immersing BC membrane in the calcium and silicate solutions by turns with different cycle times and characterized. The results indicated that the CaSiO3 particles were homogeneously dispersed on the surface of nanofibers with the effect of BC template when two cycles of soaking proceed, during which the fabrication of most CaSiO3 particles took place. The FT-IR reveals the strong interaction between the two parts of the BC/CaSiO3 composite. The XRD pattern demonstrated a crystal structure disruption of the cellulose aroused by CaSiO3 particle. BC/ CaSiO3 is considered to have a potential application in bone tissue field.

The synthesis of (octreotide-carboxymethyl-dextran)-modified magnetic nanoparticles (CMD-MNPs), which were characterized by FT-IR, AFM, TEM and XRD, and magnetic hysteresis, is described. Magnetic Resonance Imaging (MRI) experiments were performed on a 1.5 Tesla Magnetom Vision machine. The internalization of CMD-MNPs-OC into pancreatic cancer cells Bx-PC3 and colon cancer cells HCT-116 were investigated by transmission electron microscopy (TEM) and magnetic resonance imaging (MRI). The nanoparticles can be recognized specifically, via the somatostatin receptor, and which can be used as a T 2 MRI contrast agent. TEM and MRI results show that somatostatin receptor can deliver OC-modified MNPs into the cytoplasm of a cancer cell line.

Ferrocene (Fc) and its conjugates have attracted considerable attention in recent years due to their unique electrochemical behavior and significant biological activities such as antitumor, antimalarial, and antifungal. Arg-Gly-Asp (RGD)-containing peptides, because of their selective binding to integrins which are highly expressed in tumor-induced angiogenesis, play a key role in cancer targeted therapy. In this study, Fc–RGD and Fc–Am–RGD (Fc: ferrocenoyl; Am: 6-aminohexanoic acid) conjugates were synthesized, and the antitumor activities in vitro were investigated. The cell uptake of the conjugates by B16 murine melanoma cells was measured using HPLC-electrochemical method. The antitumor activities of the conjugates were also evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and flow cytometric measurements. The experimental results revealed that Fc–RGD and Fc–Am–RGD exhibit more effective antitumor activities than their parent compounds RGD and Fc-COOH. Moreover, it is found that Fc–Am–RGD yields the lowest IC 50 values of 5.2 ± 1.4 μM toward B16 cells. The HPLC-electrochemical studies confirmed that the insertion of flexible alkyl spacer Am between Fc and RGD significantly increases the cell uptake toward B16 cells and consequently improves the antitumor activity. Our results suggest that Fc–RGD and Fc–Am–RGD conjugates are potential candidates for cancer treatment.

Background: Radix Astragali mainly contains saponins, polysaccharides, flavonoids, amino acids and other chemical constituents of which total astragalosides have immunomodulatory, anti-viral, hepatoprotective, and gastric mucosa protective effects. Objective: To investigate the process conditions for extraction, purification and enrichment of total astragalosides by macroporous adsorption resin, and to study the inhibitory effect of total astragalosides on growth of human gastric cancer cell line MKN-74. Methods: UV spectrophotometry was applied to determine the adsorption and desorption capacity of macroporous adsorption resin on total astragaloside content, MTT assay was used to determine the inhibition of MKN-74 cell growth by total astragalosides. Results: The dynamic adsorption performance of DA201 adsorption resin was examined, and the dynamic adsorption curve of total astragalosides on DA201 resin column was plotted. Meanwhile, eluent and elution flow rate were investigated, the results showed that the choice of eluent of 80% ethanol, and a flow rate of 5 BV/h could maximize the yield of total astragalosides. MTT assay found that astragalosides could relatively pronouncedly inhibit the proliferation of MKN-74 cells, and the inhibitory effect was enhanced with the increase of astragaloside dose and the extension of processing time, which showed a dose-and time-dependence. Conclusion: DA201 resin can effectively enrich total astragalosides, total astragalosides have an inhibitory effect on growth of MKN-74 cells.Keywords: Total Astragalosides, DA201 Resin, MKN-74 CellAfrican Health sciences Vol 14 No. 1 March 2014