Traditional Uses, Chemical Constituents and Pharmacological Activities of the Toona sinensis Plant.

Toona sinensis (A. Juss.) Roem., which is widely distributed in China, is a homologous plant resource of medicine and food. The leaves, seeds, barks, buds and pericarps of T. sinensis can be used as medicine with traditional efficacy. Due to its extensive use in traditional medicine in the ancient world, the T. sinensis plant has significant development potential. In this review, 206 compounds, including triterpenoids (1-133), sesquiterpenoids (134-135), diterpenoids (136-142), sterols (143-147), phenols (148-167), flavonoids (168-186), phenylpropanoids (187-192) and others (193-206), are isolated from the T. sinensis plant. The mass spectrum cracking laws of representative compounds (64, 128, 129, 154-156, 175, 177, 179 and 183) are reviewed, which are conducive to the discovery of novel active substances. Modern pharmacological studies have shown that T. sinensis extracts and their compounds have antidiabetic, antidiabetic nephropathy, antioxidant, anti-inflammatory, antitumor, hepatoprotective, antiviral, antibacterial, immunopotentiation and other biological activities. The traditional uses, chemical constituents, compound cracking laws and pharmacological activities of different parts of T. sinensis are reviewed, laying the foundation for improving the development and utilization of its medicinal value.

Enhancing oxidation reaction over Pt-MnO2 catalyst by activation of surface oxygen.

Formaldehyde (HCHO) and carbon monoxide (CO) are both common air pollutants and hazardous to human body. It is imperative to develop the catalyst that is able to efficiently remove these pollutants. In this work, we activated Pt-MnO2 under different conditions for highly active oxidation of HCHO and CO, and the catalyst activated under CO displayed superior performance. A suite of complementary characterizations revealed that the catalyst activated with CO created the highly dispersed Pt nanoparticles to maintain a more positively charged state of Pt, which appropriately weakens the Mn-O bonding strength in the adjacent region of Pt for efficient supply of active oxygen during the reaction. Compared with other catalysts activated under different conditions, the CO-activated Pt-MnO2 displays much higher activity for oxidation of HCHO and CO. This research contributes to elucidating the mechanism for regulating the oxidation activity of Pt-based catalyst.

Immunogenic exosome-encapsulated black phosphorus nanoparticles as an effective anticancer photo-nanovaccine.

Tumor vaccines are a promising form of cancer immunotherapy, but difficulties such as neo-antigen identification, activation of immune cells, and tumor infiltration prevent their clinical breakthrough. Interestingly, nanotechnology-based photothermal therapy (PTT) has great potential to overcome these barriers. Previous studies have shown that serum exosomes (hEX) from hyperthermia-treated tumor-bearing mice displayed an array of patient-specific tumor-associated antigens (TAAs), and strong immunoregulatory abilities in promoting dendritic cell (DC) differentiation and maturation. Here, we developed a tumor vaccine (hEX@BP) by encapsulating black phosphorus quantum dots (BPQDs) with exosomes (hEX) against a murine subcutaneous lung cancer model. In comparison with BPQDs alone (BP), hEX@BP demonstrated better long-term PTT performance, greater elevation of tumor temperature and tumor targeting efficacy in vivo. Vaccination with hEX@BP in combination with PTT further demonstrated an outstanding therapeutic efficacy against established lung cancer, and promoted the infiltration of T lymphocytes into the tumor tissue. Our findings demonstrated that hEX@BP might be an innovative cancer photo-nanovaccine that offers effective immuno-PTT against cancers.

Eradication of tumor growth by delivering novel photothermal selenium-coated tellurium nanoheterojunctions.

Two-dimensional nanomaterial-based photothermal therapy (PTT) is currently under intensive investigation as a promising approach toward curative cancer treatment. However, high toxicity, moderate efficacy, and low uniformity in shape remain critical unresolved issues that hamper their clinical application. Thus, there is an urgent need for developing versatile nanomaterials to meet clinical expectations. To achieve this goal, we developed a stable, highly uniform in size, and nontoxic nanomaterials made of tellurium-selenium (TeSe)-based lateral heterojunction. Systemic delivery of TeSe nanoparticles in mice showed highly specific accumulation in tumors relative to other healthy tissues. Upon exposure to light, TeSe nanoparticles nearly completely eradicated lung cancer and hepatocellular carcinoma in preclinical models. Consistent with tumor suppression, PTT altered the tumor microenvironment and induced immense cancer cell apoptosis. Together, our findings demonstrate an exciting and promising PTT-based approach for cancer eradication.

Promising hen egg-derived proteins/peptides (EDPs) for food engineering, natural products and precision medicines.

Hen eggs (HEs) provide valuable nutrients for humans, including proteins, carbohydrates, lipids and vitamins. Recent studies revealed a number of novel egg-derived proteins/peptides (EDPs), and EDPs may play a crucial role in food industry and medical therapy. First, these EDPs were purified from the enzyme-catalyzed hydrolysates of egg proteins and were characterized by biochemical assays such as gel electrophoresis, HPLC, mass spectrometry, proteomic and peptideomic analysis, etc. Second, some EDPs can be used as nontoxic bio-preservatives and functional nutraceuticals for replacing harmful sodium nitrite, inhibiting foodborne pathogens, promoting metal-ion absorption and improving meat-product quality, and these new features will be widely used in the field of food production. Third, novel medical properties of EDPs comprise anti-oxidative, anti-microbial, anti-inflammatory and anti-nociceptive activities, which will benefit prevention of cardiovascular diseases, cancers, diabetic mellitus, immune disorders, etc. In summary, this review gives a real insight into the novel nutritional, biological and medical functions of EDPs, predictably facilitating the applications of EDPs in production of nutritive supplements, functional nutraceuticals and therapeutic medicines.

Formation and characterization of the micro-size granular sludge in denitrifying sulfur-conversion associated enhanced biological phosphorus removal (DS-EBPR) process.

Denitrifying Sulfur conversion-associated Enhanced Biological Phosphorus Removal (DS-EBPR) bioprocess has been recently developed for saline sewage treatment. This study investigated the applicability of granulation technology in DS-EBPR by long-term operation (272 days) of a lab-scale reactor to cultivate sludge granules, then analyzed important physicochemical and biological properties. The findings of this research showed that the net P removal and denitrification efficiencies in DS-EBPR were 80% and 98%, respectively. The average particle size was about 100 µm, and the ratio of SVI5 and SVI30 was <1.3, indicating the activated sludge was well aggregated as micro-granules. The dry density was between 32 and 56 mg/mL, and the specific surface area was 28 m2/g, demonstrating good microporous structure. FISH reveals absence of PAOs, but enriched with SRB (predominant) and denitrifying bacteria in the DS-EBPR granular sludge. Overall, this study provided essential characterization information of DS-EBPR granular sludge which can be used for future development.

A rat model for studying electroacupuncture analgesia on acute visceral hyperalgesia.

The aim of this study was to establish an appropriate rat model to study the effect of electroacupuncture (EA) analgesia on acute visceral hyperalgesia. Adult rats received colorectal instillation with different concentrations of acetic acid (AA). Treatment with EA was performed for 30 min at bilateral acupoints of ST-36 and ST-37 in the hind limbs. The visceral sensation of all rats was quantified by scores of abdominal withdrawal reflex (AWR) and discharges of rectus abdominis electromyogram (EMG) in response to colorectal distension (CRD). Two hours after instillation of saline (no AA), 1%, 2%, and 4% AA, there were no, slight, moderate and severe visceral hyperalgesia, respectively. Application of EA significantly relieved the visceral hyperalgesia induced by 2% but not 4% AA. The results suggest that 2% AA acute visceral hyperalgesia in adult rats responds well to EA treatment. This may offer an appropriate model for the investigation of EA effects.

Immunogenicity differences of a 15-valent pneumococcal polysaccharide conjugate vaccine (PCV15) based on vaccine dose, route of immunization and mouse strain.

Pneumococcal disease continues to be a medical need even with very effective vaccines on the market. Globally, there are extensive research efforts to improve serotype coverage with novel vaccines; therefore, conducting preclinical studies in different animal models becomes essential. The work presented herein focuses on evaluating a 15-valent pneumococcal conjugate vaccine (PCV15) in mice. Initially we evaluated several doses of PCV15 in Balb/c mice. The optimal vaccine dose was determined to be 0.4µg per pneumococcal polysaccharide (PS) (0.8µg of 6B) for subsequent studies. This PS dose was chosen for PCV evaluation in mice based on antibody levels determined by multiplexed electrochemiluminescent (ECL) assays, T-cell responses following in vitro stimulation with CRM197 peptides and protection from pneumococcal challenge. We then selected four mouse strains for evaluation: Balb/c, C3H/HeN, CD1 and Swiss Webster (SW), immunized with PCV15 by either intraperitoneal (IP) or intramuscular (IM) routes. We assessed IgG responses by ECL assays and functional antibody activity by multiplexed opsonophagocytic assays (MOPA). Every mouse strain evaluated responded to all 15 serotypes contained in the vaccine. Mice tended to have lower responses to serotypes 6B, 23F and 33F. The IP route of immunization resulted in higher antibody titers for most serotypes in Balb/c, C3H and SW. CD1 mice tended to respond similarly for most serotypes, regardless of route of immunization. Similar trends were observed with the four mouse strains when evaluating functional antibody activity. Given the differences in antibody responses based on mouse strain and route of immunization, it is critical to evaluate pneumococcal vaccines in multiple animal models to determine the optimal formulation before moving to clinical trials.

Downregulation of the spinal NMDA receptor NR2B subunit during electro-acupuncture relief of chronic visceral hyperalgesia.

The involvement of spinal NR2B, a N-methyl-D-aspartate (NMDA) receptor subunit, in the therapeutic effect of electro-acupuncture (EA) on chronic visceral hyperalgesia was investigated. Chronic visceral hyperalgesia was induced using an irritable bowel syndrome (IBS) model in rats. Graded colorectal distention (CRD) stimuli at strengths of 20, 40, 60 and 80 mmHg were applied, and behavioral tests were performed to measure the abdominal withdrawal reflex (AWR) in response to the CRD stimuli and assess the severity of the visceral hyperalgesia. Rats were randomly divided into four groups: normal intact (control) group, IBS model (model) group, EA-treated IBS rats (EA) group and sham EA-treated IBS rats (sham EA) group. For the EA treatment, electric stimuli were applied through needles inserted into two acupoints [Zu-san-li (ST-36) and Shang-ju-xu (ST-37)] in both hind limbs, while the sham EA treatment consisted of only the insertion of needles into these same acupoints without an application of electric stimuli. Our results showed that AWR scores of the model group responding to CRD stimuli of 20, 40, 60 and 80 mmHg were significantly increased. These increased scores subsequently decreased following EA treatment (P < 0.05) compared with those for the other groups. The expression of NR2B in the superficial laminae (SDH, laminae I and II), nucleus proprius (NP, laminae III and IV), neck of the dorsal horn (NECK, laminae V and VI) and central canal region (lamina X) at thoracolumbar (T13-L2) and lumbosacral (L6-S2) segmental level significantly increased in the model group versus the control group (P < 0.05) and significantly decreased after EA treatment (P < 0.05). There were no significant changes in neither AWR scores nor expression of the NR2B subunit in these spinal regions after the sham EA treatment. These results confirm that EA can relieve chronic visceral hyperalgesia in IBS model rats and suggest that such an effect is possibly mediated through the downregulation of the NR2B subunits of NMDA at the spinal level.

Electroacupuncture analgesia with different frequencies is mediated via different opioid pathways in acute visceral hyperalgesia rats.

AIMS: To investigate the efficacy of electroacupuncture (EA) alleviation of acute visceral hyperalgesia, the frequency dependence of this efficacy, and the difference in endogenous opioid pathways as underlying mechanism explaining the frequency dependence. MAIN METHODS: A visceral hyperalgesia model was established by colorectal instillation of 2% acetic acid (AA) in adult rats. EA treatment at 2Hz, 100Hz, 2/100Hz and sham EA were performed at two bilateral acupoints, ST-36 and ST-37, in the hind-limbs. Naloxone (NLX, 2mg/kg) was administered intraperitoneally 5min before the application of EA. The visceral sensation was quantified by scores of abdominal withdrawal reflex (AWR) and values of rectus abdominis electromyograms (EMGs) in response to colorectal distension (CRD). KEY FINDINGS: Acute visceral hyperalgesia was produced by instillation of AA. The hyperalgesia reached the peak at 2h, and maintained steadily for >6h. EA treatment at 2Hz, 100Hz and 2/100Hz attenuated the acute hyperalgesia, and the attenuation lasted for 2.5h, 2h and 3h, respectively. Sham EA produced no such effect. The analgesic potencies of EA treatment at 2Hz, 100Hz and 2/100Hz were completely blocked, almost not affected, and partially blocked by NLX. In the latter two frequencies, the analgesic durations were shortened to 1.5h and 2h, respectively. SIGNIFICANCE: EA can alleviate acute visceral hyperalgesia. Effective EA analgesia at different frequencies are potentially mediated via different endogenous opioid pathways.

Purified anthocyanin supplementation reduces dyslipidemia, enhances antioxidant capacity, and prevents insulin resistance in diabetic patients.

BACKGROUND: Oxidative stress plays an essential role in the pathogenesis of type 2 diabetes. Anthocyanin, a natural antioxidant, has been reported to reduce oxidative stress and to attenuate insulin resistance and diabetes in animal models; however, the translation of these observations to humans has not been fully tested. OBJECTIVE: This study was designed to investigate the effects of purified anthocyanins on dyslipidemia, oxidative status, and insulin sensitivity in patients with type 2 diabetes. METHODS: A total of 58 diabetic patients were given 160 mg of anthocyanins twice daily or placebo (n = 29/group) for 24 wk in a randomized, placebo-controlled, double-blind trial. Participants and investigators were masked to treatment allocation. RESULTS: Anthocyanin supplementation significantly decreased serum LDL cholesterol (by 7.9%; P < 0.05), triglycerides (by 23.0%; P < 0.01), apolipoprotein (apo) B-48 (by 16.5%; P < 0.05), and apo C-III (by 11.0%; P < 0.01) and increased HDL cholesterol (by 19.4%; P < 0.05) compared with placebo after the 24-wk intervention. In addition, patients in the anthocyanin group showed higher total radical-trapping antioxidant parameter and ferric ion reducing antioxidant power values than did patients in the placebo group (both P < 0.05). Serum concentrations of 8-iso-prostaglandin F2α, 13-hydroxyoctadecadienoic acid, and carbonylated proteins in patients in the anthocyanin group were significantly less than in patients in the placebo group (23.4%, 25.8%; P < 0.01 and 20%; P = 0.022, respectively). Furthermore, supplementation with anthocyanin lowered fasting plasma glucose (by 8.5%; P < 0.05) and homeostasis model assessment for insulin resistance index (by 13%; P < 0.05), and elevated serum adiponectin (by 23.4%; P < 0.01) and ß-hydroxybutyrate (by 42.4%; P = 0.01) concentrations compared with placebo supplementation. CONCLUSION: These findings demonstrate that anthocyanin supplementation exerts beneficial metabolic effects in subjects with type 2 diabetes by improving dyslipidemia, enhancing antioxidant capacity, and preventing insulin resistance. This trial was registered at www.clinicaltrials.gov as NCT02317211.

A case of advanced lung cancer with malignant pericardial effusion treated by intrapericardial Cinobufacini injection instillation.

Malignant pericardial effusion is one of the severe complications in advanced lung cancer patients, seriously affecting the patient's cardiopulmonary function and even life. Pericardial drainage and instillation of anti-neoplastic drugs in the pericardial cavity seems to offer the best chance of controlling pericardial effusion. We reported a case concerning treatment of a 63-year-old man in advanced lung cancer with a large amount of pericardial effusion. We utilized pericardium puncture and drainage combined with instillation of Cinobufacini injection in the pericardial cavity to treat pericardial effusion. After treatment with Cinobufacini injection for two weeks, the patient was followed up in one month to assess effectiveness, quality of life, and safety. We found that the cardiac tamponade symptoms such as difficult breathing, chest distress, and palpitations were significantly relieved. The patient's quality of life was effectively improved with KPS scores increased. We also found that the levels of tumor marker CA-125 in the pericardial effusion decreased (from 340.80 U/mL to 34.85 U/mL) and pericardium B ultrasound showed that the quantity of pericardial effusion reduced significantly (from 2.5 cm to 0.6 cm). Furthermore, there were little gastrointestinal adverse reactions and myelosuppression in the patient after instillation of the Cinobufacini injection. Taken together, this provides a new way for treating cancerous pericardial effusion, especially for patients who cannot tolerate instillation of chemotherapy drugs, and is worthwhile to carry out more standardized studies in the future.

Anthocyanin increases adiponectin secretion and protects against diabetes-related endothelial dysfunction.

Adiponectin is an adipose tissue-secreted adipokine with beneficial effects on the cardiovascular system. In this study, we evaluated a potential role for adiponectin in the protective effects of anthocyanin on diabetes-related endothelial dysfunction. We treated db/db mice on a normal diet with anthocyanin cyanidin-3-O-ß-glucoside (C3G; 2 g/kg diet) for 8 wk. Endothelium-dependent and -independent relaxations of the aorta were then evaluated. Adiponectin expression and secretion were also measured. C3G treatment restores endothelium-dependent relaxation of the aorta in db/db mice, whereas diabetic mice treated with an anti-adiponectin antibody do not respond. C3G treatment induces adiponectin expression and secretion in cultured 3T3 adipocytes through transcription factor forkhead box O1 (Foxo1). Silencing Foxo1 expression prevented C3G-stimulated induction of adiponectin expression. In contrast, overexpression of Foxo1-ADA promoted adiponectin expression in adipocytes. C3G activates Foxo1 by increasing its deacetylation via silent mating type information regulation 2 homolog 1 (Sirt1). Furthermore, purified anthocyanin supplementation significantly improved flow-mediated dilation (FMD) and increased serum adiponectin concentrations in patients with type 2 diabetes. Changes in adiponectin concentrations positively correlated with FMD in the anthocyanin group. Mechanistically, adiponectin activates cAMP-PKA-eNOS signaling pathways in human aortic endothelial cells, increasing endothelial nitric oxide bioavailability. These results demonstrate that adipocyte-derived adiponectin is required for anthocyanin C3G-mediated improvement of endothelial function in diabetes.

Anthocyanin supplementation improves HDL-associated paraoxonase 1 activity and enhances cholesterol efflux capacity in subjects with hypercholesterolemia.

CONTEXT AND OBJECTIVE: Paraoxonase 1 (PON1), an enzyme associated with high-density lipoprotein (HDL-PON1), is reported to have antioxidant and cardioprotective properties. The aim of the present study was to investigate the effects of anthocyanins on the HDL-PON1 activity and cholesterol efflux capacity in hypercholesterolemic subjects. DESIGN AND PARTICIPANTS: A total of 122 hypercholesterolemic subjects were given 160 mg of anthocyanins twice daily or placebo (n = 61 of each group) for 24 weeks in a double-blind, randomized, placebo-controlled trial. Participants and investigators were masked to treatment allocation. RESULTS: Anthocyanin consumption significantly increased HDL cholesterol and decreased low -density lipoprotein cholesterol concentrations compared with placebo (P < .018 and P < .001, respectively). Anthocyanin supplementation also increased the activity of HDL-PON1 compared with placebo (P < .001). Furthermore, cholesterol efflux capacity was increased more in the anthocyanin group (20.0% increase) than in the placebo group (0.2% increase) (P < .001). The negative correlations established between HDL-PON1 activity and the levels of lipid hydroperoxides associated with HDL confirm the relationship between PON1 activity and lipid peroxidation of lipoproteins. Furthermore, a strong positive correlation was noted between increased HDL-PON1 activity and improved cholesterol efflux capacity both before and after adjustment for HDL cholesterol and apolipoprotein AI in anthocyanin-treated subjects (both P < .001). Inhibition of HDL-PON1 activity strongly prevented the antioxidant ability of HDL and attenuated the cholesterol efflux capacity of subjects from anthocyanin group. CONCLUSIONS: Our observations suggest that the alterations of PON1 activity by anthocyanin observed in hypercholesterolemic HDL reflect a shift to an improvement of cholesterol efflux capacity of HDL and may provide a link between anthocyanin and cardioprotective effects.

Supplementation of cyanidin-3-O-ß-glucoside promotes endothelial repair and prevents enhanced atherogenesis in diabetic apolipoprotein E-deficient mice.

Atherosclerosis is accelerated in diabetes mellitus mainly due to the reduced availability and function of endothelial progenitor cells (EPCs). The purpose of this study was to determine the protective effects of the anthocyanin cyanidin-3-O-ß-glucoside (C3G) on EPC function and endothelial repair in diabetic apolipoprotein E-deficient (apoE(-/-)) mice. Diabetes mellitus was induced in 8-wk-old male apoE(-/-) mice with streptozotocin. Diabetic apoE(-/-) mice were fed the AIN-93 diet or an AIN-93 diet supplemented with C3G (0.2% wt:wt) for 6 wk. Sham-injected apoE(-/-) mice fed the AIN-93 diet served as nondiabetic controls. The endothelium-dependent relaxation response to acetylcholine in the aortas of C3G-fed mice was greater by 51% compared with diabetic mice fed the AIN-93 diet (P < 0.05) and was similar to that in nondiabetic apoE(-/-) mice. The capacity of in vitro adhesion to fibronectin, migration, and tube formation was significantly impaired in diabetic EPCs (decreased by 83, 61.9, and 74.5%, respectively, compared with nondiabetic controls; all P < 0.01), which was significantly rescued in response to C3G (increased by 3.9-, 2-, and 1.8-fold compared with diabetic EPCs, respectively; all P < 0.05). At the molecular level, the phosphorylation levels of AMP-activated protein kinase (AMPK) Thr 172 and endothelial nitric oxide synthase (eNOS) Ser1177 were higher in EPCs derived from the C3G-treated diabetic mice compared with those in nondiabetic mice. Furthermore, compared with nondiabetic controls, diabetic apoE(-/-) mice had a 3.5-fold increase in the aortic lesion area, which was lowered by 45% in C3G-fed diabetic mice. This study extends our current knowledge that C3G improves the impairment of EPC function, enhances endothelial repair, and thus limits accelerated atherogenesis caused by diabetes. Our findings emphasize the potential utility of anthocyanin in the prevention and treatment of diabetic vascular complications.

Supplementation with cyanidin-3-O-ß-glucoside protects against hypercholesterolemia-mediated endothelial dysfunction and attenuates atherosclerosis in apolipoprotein E-deficient mice.

In this study, we investigated the protective effects of the anthocyanin cyanidin-3-O-ß-glucoside (C3G) on hypercholesterolemia-induced endothelial dysfunction in apoE-deficient (apoE(-/-)) mice. In the prevention study, twenty 8-wk-old male apoE(-/-) mice (n = 10/group) were fed a high-fat, cholesterol-rich diet (HCD) or the HCD supplemented with C3G (2 g/kg diet) for 8 wk. The endothelium-dependent relaxation response to acetylcholine in the aortas of the C3G-fed mice was greater compared with those fed the HCD (P < 0.05). The atherosclerotic plaque area in the aortic sinus of mice fed the C3G diet was lowered by 54% compared with those fed the HCD (P < 0.01). Mice fed C3G had greater expression of the ATP-binding cassette transporter G1 (ABCG1) and lower cholesterol, mainly 7-ketocholesterol (7-KC), concentrations than those fed the HCD. Superoxide production and lipid hydroperoxides in aorta were lower in mice fed C3G compared with those fed the HCD. The phosphorylation levels at Ser1177 of endothelial NO synthase (eNOS) and the production of cyclic GMP (cGMP) in aorta were greater in C3G-fed mice than in HCD-fed mice. In the therapy study, apoE(-/-) mice were fed the HCD for 8 wk and then continued to receive the HCD or were switched to the HCD supplemented with C3G (2 g/kg diet) for another 8 wk. The established endothelial dysfunction and atherosclerosis were reversed, accompanied by greater ABCG1 expression in aorta, lower cholesterol and 7-KC concentrations, and greater generation of cGMP in mice fed C3G compared with those fed the HCD. Taken together, our results show that the anthocyanin C3G prevents or reverses hypercholesterolemia-induced endothelial dysfunction by inhibiting cholesterol and 7-oxysterol accumulation in the aorta and the subsequent decrease in superoxide production, thereby preserving eNOS activity and NO bioavailability.

Pre-clinical evaluation of a 15-valent pneumococcal conjugate vaccine (PCV15-CRM197) in an infant-rhesus monkey immunogenicity model.

The incidence of invasive pneumococcal disease (IPD), caused by the approximately 91 serotypes of Streptococcus pneumoniae (PN), varies geographically and temporally as a result of changing epidemiology and vaccination patterns as well as due to regional measurement differences. Prevnar(®) (Pfizer), the first licensed pneumococcal conjugate vaccine (PCV), comprises polysaccharides (PS) from 7 serotypes conjugated to the mutant diphtheria toxin carrier protein, CRM197. In the United States and elsewhere, this vaccine has been highly efficacious in reducing the incidence of IPD caused by vaccine serotypes, however, the incidence of non-vaccine serotypes (e.g., 19A, 22F, and 33F) has increased, resulting in the need for vaccines with higher valencies. In response, 10- and 13-valent PCVs have recently been licensed. To further increase serotype coverage, we have developed a 15-valent PCV containing PS from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F conjugated to CRM197 and formulated on aluminum phosphate adjuvant. Vaccine immunogenicity was evaluated in infant rhesus monkeys since they, like human infants, respond poorly to unconjugated PN PS. Infant (2-3 month old) rhesus monkeys were vaccinated three times with PCV-15 or Prevnar(®) at 2 month intervals, and serotype-specific IgG antibodies were measured using a multiarray electrochemiluminescence (ECL) assay. The results indicate that antibody responses to PCV-15 and Prevnar(®) were comparable for the 7 common serotypes and that post-vaccination responses to PCV-15 were >10-fold higher than baseline for the 8 additional serotypes.

[Exploration on eighteen incompatible medicaments of chest pain prescriptions based on association rules mining].

OBJECTIVE: To investigate the laws of eighteen incompatible medicaments of the chest pain prescriptions based on association rules mining. METHOD: The database of chest pain prescription was established and then the chest pain prescriptions composed of eighteen incompatible medicaments were screened. The dynasty, couplet medicines, the property and flavor of drugs and preparation form were analyzed with the frequent item sets and corresponding analysis methods. RESULT: Eight hundred and fifty chest pain prescriptions were collected, and 88 of them contained eighteen incompatible medicaments, taking 10.3% of all; the applications of ancient and modern chest pain prescriptions containing eighteen incompatible medicaments are significant difference (P < 0.05). Ancient formulas, mainly focus on the eastern jin dynasty and tang dynasty, are more often used than the modern formulas. The most common anti-drugs is on the Fuzi-Pinellia, Chuanwu-Pinellia; the property and flavor of drugs is bitter cold most closely; the decoction of the formulas is mostly used. CONCLUSION: Eighteen incompatible medicaments account for about ten percent of the chest pain prescription, not an uncommon side. There are certain rules for application of anti-drug compatibility to treat chest pain.

Inhibition of SNF1-related protein kinase1 activity and regulation of metabolic pathways by trehalose-6-phosphate.

Trehalose-6-phosphate (T6P) is a proposed signaling molecule in plants, yet how it signals was not clear. Here, we provide evidence that T6P functions as an inhibitor of SNF1-related protein kinase1 (SnRK1; AKIN10/AKIN11) of the SNF1-related group of protein kinases. T6P, but not other sugars and sugar phosphates, inhibited SnRK1 in Arabidopsis (Arabidopsis thaliana) seedling extracts strongly (50%) at low concentrations (1-20 microM). Inhibition was noncompetitive with respect to ATP. In immunoprecipitation studies using antibodies to AKIN10 and AKIN11, SnRK1 catalytic activity and T6P inhibition were physically separable, with T6P inhibition of SnRK1 dependent on an intermediary factor. In subsequent analysis, T6P inhibited SnRK1 in extracts of all tissues analyzed except those of mature leaves, which did not contain the intermediary factor. To assess the impact of T6P inhibition of SnRK1 in vivo, gene expression was determined in seedlings expressing Escherichia coli otsA encoding T6P synthase to elevate T6P or otsB encoding T6P phosphatase to decrease T6P. SnRK1 target genes showed opposite regulation, consistent with the regulation of SnRK1 by T6P in vivo. Analysis of microarray data showed up-regulation by T6P of genes involved in biosynthetic reactions, such as genes for amino acid, protein, and nucleotide synthesis, the tricarboxylic acid cycle, and mitochondrial electron transport, which are normally down-regulated by SnRK1. In contrast, genes involved in photosynthesis and degradation processes, which are normally up-regulated by SnRK1, were down-regulated by T6P. These experiments provide strong evidence that T6P inhibits SnRK1 to activate biosynthetic processes in growing tissues.

Molecular cloning of an arabidopsis homologue of GCN2, a protein kinase involved in co-ordinated response to amino acid starvation.

DNA homologous to the yeast ( Saccharomyces cerevisiae) protein kinase gene, GCN2, was amplified from arabidopsis [ Arabidopsis thaliana (L.) Heynh.] RNA and given the name AtGCN2. The AtGCN2 peptide sequence included adjacent protein kinase and histidyl tRNA synthetase-like domains and showed 45% sequence identity with the GCN2 peptide sequence in the protein kinase domain. AtGCN2 transcripts were detectable in RNA from roots, leaves, stems, buds, flowers, siliques and seedlings. GCN2 is required for yeast cells to respond to amino acid starvation. Expression of AtGCN2 in yeast gcn2 mutants complemented the mutation, enabling growth in the presence of sulfometuron methyl, an inhibitor of branched-chain amino acid biosynthesis, and 3-aminotriazole, an inhibitor of histidine biosynthesis.