Inhibitory effects of essential oils from Asteraceae plant against pathogenic fungi of Panax notoginseng.

AIMS: Diseases caused by pathogenic fungi was a major constrain in increasing productivity and improving quality of Panax notoginseng. The aim of this research was to evaluate the inhibitory activity of essential oils (EOs) from Asteraceae family, Chrysanthemum indicum and Laggera pterodonta, against pathogenic fungi of P. notoginseng. METHODS AND RESULTS: The antifungal activity was investigated using multiple methods, disclosing that the EOs from C. indicum and L. pterodonta are active against hypha growth of different fungi but with different degrees of potency. Checkerboard testing indicated that the combination of EOs with hymexazol had synergistic effect against Pythium aphanidermatum, and exhibited additive effects against bulk of targeted pathogenic fungi. Besides, we found that the baseline sensitivity of Fusarium oxysporum to L. pterodonta EOs was higher than those of C. indicum by means of mycelium growth rate method. Finally, the practicability of those EOs as plant pesticide was confirmed by in vivo model showing that EOs can significantly inhibit the occurrence of root rot of P. notoginseng caused by F. oxysporum. CONCLUSION: Those studies suggest that the EOs from C. indicum and L. pterodonta had the potential to develop into new pollution-free pesticides for the protection of precious Chinese herbal medicines. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provided a new way of biological control for overcoming the frequent diseases occurrence of P. notoginseng.

[Association of fibroblast growth factor 23 with age-related cardiac diastolic function subclinical state in a healthy Chinese population].

Objective: To determine the association of serum fibroblast growth factor-23 concentrations with age-related cardiac diastolic function subclinical state and whether this association differs by sex. Methods: Seven hundred sixteen healthy subjects (aged 35-89 years, 68.4% female) were selected from National Basic Research Program of China (973 Program-China Medical University subsection) between January 2014 and February 2015 and assigned into 4 groups according to sex and age:< 60 years old male and female group, ≥ 60 years old male and female group. Blood biochemical indicators and general clinical data of the subjects were measured. The glomerular filtration rate (eGFR) were estimated using the Modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI-ASIA) equation. The fibroblast factor 23 (FGF-23), C-reactive protein (CRP) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Cardiac structure and function parameters including left atrial diameter (LAD), inter-ventricular septum thickness (IVST), left ventricle posterior wall thickness (LVPWT), left ventricle mass index (LVMI),left atrial mass index (LAVI) and the ratio of peak velocity of early filling to the septal early peak diastolic mitral annulus velocity(E/e') were measured by echocardiography. Association between serum FGF-23 and aging-related diastolic function subclinical status was analyzed by binary Logistic regression analysis. Results: (1) Serum log-transformed FGF-23 levels were significantly higher in males than in females [(2.0±0.3) ng/L vs (1.9±0.4) ng/L, P<0.05]. (2) Cardiac diastolic function gradually decreased with age, and age related cardiac diastolic function decline of female was significantly higher than males[E/e':<60 years old male group (7.6±2.6), ≥ 60 years old male group (8.6±2.7), P<0.01;<60 years old female group (8.3±2.3), ≥ 60 years old female group (9.5±3.1), P<0.01; LAVI:<60 years old female group (14±5) ml/m(2), ≥ 60 years old female group (16±5) ml/m(2), P<0.01]. (3) Serum FGF-23 was significantly positively correlated with age (r=0.089, P<0.05) and LAVI (r=0.084, P<0.05) in total study population while with E/e' (r=0.149, P<0.05) only in males. There was no significant correlation between serum FGF-23 and cardiac diastolic function parameters in females. (4) Binary Logistic regression analysis showed that median and high FGF-23 were independently associated with age-related cardiac diastolic function decline (OR=2.831, 95% CI: 1.144-7.009, P=0.024; OR=2.548, 95% CI: 1.053-6.163, P=0.038) in males. Conclusions: Serum FGF-23 concentrations are associated with age-related cardiac diastolic function subclinical state in a healthy Chinese population. High levels of FGF-23 are independently associated with age-related cardiac diastolic function decline in males.

Hox genes reveal genomic DNA variation in tetraploid hybrids derived from Carassius auratus red var. (female) × Megalobrama amblycephala (male).

BACKGROUND: Allotetraploid F1 hybrids (4nF1) (AABB, 4n = 148) were generated from the distant hybridization of Carassius auratus red var. (RCC) (AA, 2n = 100) (♀) × Megalobrama amblycephala (BSB) (BB, 2n = 48) (♂). It has been reported that Hox gene clusters are highly conserved among plants and vertebrates. In this study, we investigated the genomic organization of Hox gene clusters in the allotetraploid F1 hybrids and their parents to investigate the polyploidization process. RESULTS: There were three copies of Hox genes in the 4nF1 hybrids, two copies in RCC and one copy in BSB. In addition, obvious variation and pseudogenization were observed in some Hox genes from 4nF1. CONCLUSION: Our results reveal the influence of polyploidization on the organization and evolution of Hox gene clusters in fish and also clarify some aspects of vertebrate genome evolution.

SERS detection of R6G based on a novel graphene oxide/silver nanoparticles/silicon pyramid arrays structure.

We present a novel surface-enhanced Raman scattering (SERS) substrate based on graphene oxide/silver nanoparticles/silicon pyramid arrays structure (GO/Ag/PSi). The SERS behaviors are discussed and compared by the detection of R6G. Based on the contrast experiments with PSi, GO/PSi, Ag/PSi and GO/AgA/PSi as SERS substrate, the perfect bio-compatibility, good homogeneity and chemical stability were confirmed. We also calculated the electric field distributions using Finite-difference time-domain (FDTD) analysis to further understand the GO/Ag/PSi structure as a perfect SERS platform. These experimental and theoretical results imply that the GO/Ag/PSi with regular pyramids array is expected to be an effective substrate for label-free sensitive SERS detections in areas of medicine, food safety and biotechnology.

[Clinical diagnostic practices for Chinese developmental dyslexia].

Objective: To explore the optimization of the standardized assessment tool for clinical diagnosis of Chinese developmental dyslexia (DD). Methods: A cross-sectional study was conducted from May to December 2023, in which 130 primary school children in grades 1 to 3 with clinical signs of literacy lag and positive screening results on the screening scales were recruited from the outpatient clinic of Child Health Care Medical Division, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine. Chinese dyslexia screening behavior checklist for primary students (CDSBC) was used as the screening scales, and supplemented by dyslexia checklist for Chinese children. Referring to the standard procedure of the"expert advice on diagnosis and intervention of Chinese developmental dyslexia", the developmental dyslexia scale for standard mandarin (DDSSM) was used to evaluate the children's literacy-related cognitive abilities and conduct the diagnostic assessment, and divided the children into learning backward group and the DD group. The t-test and χ2 test were used to compare the differences in the distribution of intelligence, literacy and attention deficit hyperactivity disorder between the two groups. Spearman's correlation was used to analyze the correlation between the scores for each cognitive ability in the DDSSM and the CDSBC. Results: Of the 130 children, 90 were male, aged (8.3±1.0) years; 40 were female, aged (8.1±0.9) years. A final diagnosis of DD was made in 59 cases, of which 41 were males. There was no statistically significant difference in operational intelligence quotient (101±15 vs.100±15, t=0.53, P>0.05) and statistically significant difference in literacy of DDSSM (32±5 vs.21±4, t=11.56, P<0.001) between the learning backward group and the DD group. Eighteen cases (25.4%) of the learning backward group were children with attention deficit subtype attention deficit hyperactivity disorder (ADHD-I), and 16 cases (27.1%) in DD group, the difference in incidence between the two groups was not statistically significant (χ2=0.05, P>0.05). There were correlations between the DDSSM (for oral vocabulary, morphological awareness and orthographic awareness) and the CDSBC total score (r=-0.42, -0.32, -0.35, all P<0.01), but the correlations for visuospatial perception and rapid automatized naming with CDSBC total score were not statistically significant (r=-0.09 and -0.20,both P>0.05). Conclusion: For literacy-related cognitive abilities, screening scales CDSBC are not sufficiently useful for assessment, so the introduction of standardized assessment tools DDSSM is an optimization of the clinical diagnosis of Chinese DD, which is crucial for achieving accurate diagnosis and intervention.

Comparison of 5-fluorouracil pharmacokinetics in patients receiving continuous 5-fluorouracil infusion and oral uracil plus N1-(2'-tetrahydrofuryl)-5-fluorouracil.

Plasma 5-fluorouracil (5-FU) levels were compared in the same patients after approximately equimolar doses (1.9 mmol/ m2/day) of 5-day continuous i.v. infusion of 5-FU (CIFU) and oral administration of a formulation of two combined pharmacological agents, uracil (U) plus N1-(2'-tetrahydrofuryl)-5-fluorouracil (ftorafur or FT), a prodrug of 5-FU. Ten patients received CIFU for 5 days, then, after a week wash-out period, began the 28-day oral UFT regimen, which was given in three daily divided doses. Following 1 h of CIFU, the plasma 5-FU levels reached a steady state of 0.6+/-0.2 microM (mean+/-SD; day 1), which was maintained for the entire 5-day infusion period (0.6+/-0.1 microM). In contrast, the maximum 5-FU concentrations (Cpmax) generated from oral UFT at 1 h after dose administration on days 1 and 5 were 2.1+/-1.5 microM and 2.3+/-1.9 microM, respectively, which were higher than the steady-state levels during CIFU. These high 5-FU levels disappeared with an apparent elimination half-life (tl/2,beta) of 5.2+/-2.4 h (day 1) and 7.2+/-3.9 h (day 5). On day 1 of both regimens, CIFU patients had significantly larger 5-FU area under the concentration versus time curve (AUC0-8h) values (4.4+/-1.3 microM.h) than the AUC value when they received the UFT regimen (2.6+/-1.7 microM.h; P = 0.02). However, by day 5, there were no significant differences between AUC0-8 h values in patients receiving CIFU and UFT, respectively (4.8+/-1.5 microM.h versus 3.8+/-2.2 microM.h; P = 0.30)]. On day 5, the average concentration of the metabolite 5-FU at steady-state (Css,aver) within dose interval of 8 h (0.48+/-0.28 microM) for the oral UFT treatment is comparable with the Cpss values of 5-FU from CIFU-treated patients. The post-UFT generated 5-FU pharmacokinetic parameters (higher Cp(mx, comparable Css,aver, equal AUC values, and longer apparent t1/2,beta of 5-FU) may make oral UFT a preferred method of delivering this fluoropyrimidine over CIFU. In addition, oral UFT would eliminate the incidence of venous thrombosis and catheter-related infections sometimes seen in patients treated with CIFU. Furthermore, the convenience and decreased cost of oral administration may be preferable for many patients, particularly those receiving 5-FU for palliation.

Oral uracil and Ftorafur plus leucovorin: pharmacokinetics and toxicity in patients with metastatic cancer.

PURPOSE: To assess the pharmacokinetics of Ftorafur (tegafur, FT), 5-fluorouracil (5-FU), and uracil in 31 cancer patients who were enrolled in phase I studies of oral uracil and FT (UFT). The correlation between pharmacokinetic parameters and toxic effects of UFT was evaluated. METHODS: Uracil and FT were orally administered in a 4:1 molar ratio at FT doses of 200-400 mg/m2 per day. Patients also received leucovorin at 150 mg/day. Daily doses were divided into three doses and administered at 8-h intervals for 28 consecutive days. Plasma FT concentrations were measured by high-performance liquid chromatography, and plasma 5-FU and uracil concentrations were determined using gas chromatography-mass spectrometry. National Institutes of Health Common Toxicity Criteria were used for assessment of toxicity. RESULTS: The concentrations of FT, 5-FU, and uracil showed wide interpatient variations. Maximum plasma concentrations (Cp(max)) of all three compounds were achieved in 0.3 to 4.0 h. At the various study doses, the terminal half-life (t 1/2beta) of FT ranged from 3.9 to 5.9 h, the area under the concentration-versus-time curve (AUC0-6h) ranged from 16,220 to 52,446 (ng/ml)h, the total clearance (ClT) ranged from 100 to 175 ml/min, and the steady-state volume of distribution (Vd(ss)) ranged from 18.3 to 28.7 l. The 5-FU generated from FT had an apparent distribution half-life (t 1/2alpha) and an apparent elimination half-life (t 1/2beta) of 0.3-1.3 h and 4.9-7.0 h, respectively. The AUC0-6h of 5-FU ranged from 120 to 325 (ng/ml)h. Uracil had a t 1/2alpha of 0.2-0.5 h and the level quickly returned to the endogenous level. The AUC0-6h for uracil ranged from 605 to 3764 (ng/ml)h, the ClT ranged from 3225 to 7748 ml/min, and the Vd(ss) ranged from 341 to 1354 l. The Cp(max) and AUC0-6h of both FT and uracil were significantly correlated with FT doses (P-values of 0.0244 and 0.0112) and with uracil doses (P-values of 0.0346 and 0.0083), respectively. In addition to interpatient variations, intrapatient variations were also observed in six patients who had pharmacology studies done on days 1 and 26+/-2 at the same study dose. We found that the repeated treatment with UFT caused cumulative increases in the values of Cp(max), Ctrough, and AUC0-6h of FT and 5-FU. The major toxic effects observed were diarrhea and nausea and vomiting. The occurrence of these toxic effects correlated significantly with the Cp(max) and AUC0-6h of 5-FU. CONCLUSIONS: The pharmacology studies showed that FT and uracil were readily absorbed orally and that FT was rapidly converted to 5-FU. The preliminary findings suggest that determination of plasma levels of 5-FU after oral administration of UFT may help predict subsequent toxic effects.

Opioid-dopaminergic mechanisms in the potentiation of d-amphetamine discrimination by interferon-alpha.

In rats trained to discriminate 0.8 mg/kg IP d-amphetamine from 1 ml/kg saline, 4 x 10(6) U/kg of recombinant human interferon-alpha (rIFN-alpha) given intramuscularly 1 h prior to tests potentiated responses elicited by 0.4 mg/kg d-amphetamine. Coadministration of the opioid receptor antagonist naloxone (1 mg/kg IP) with rIFN-alpha suppressed the potentiation of d-amphetamine by the cytokine. Opioid-dopaminergic mechanisms are proposed to explain the action of rIFN-alpha.

Activation of extracellular signal-regulated kinase by TGF-beta1 via TbetaRII and Smad7 dependent mechanisms in human bronchial epithelial BEP2D cells.

Transforming growth factor-beta1 (TGF-beta1) can activate mitogen-activated protein kinases (MAPKs) in many types of cells. The mechanism of this activation is not well elucidated. Here, we explore the role of TGF-beta/Smads signaling compounds in TGF-beta1-mediated activation of extracellular signal-regulated kinase (ERK) MAPK in human papillomavirus (HPV)-18 immortalized human bronchial epithelial cell line BEP2D and the role of TGF-beta1-induced phosphorylation of ERK in proliferation and apoptosis of BEP2D. The cell models of siRNA-mediated silencing of TGF-beta receptor type II (TbetaRII), Smad2, Smad3, Smad4, and Smad7 were employed in this study. Our results demonstrate that TGF-beta1 activates ERK in a time-dependent manner with a maximum effect at 60 min; overexpression of Smad7 increased this TGF-beta1-mediated phosphorylation of the ERK; and siRNA-mediated silencing of TbetaRII, Smad3, Smad4, and Smad7 abrogated this effect. Moreover, we observed that overexpression of Smad7 restored TGF-beta1-mediated ERK phosphorylation in Smad4 knockdown cells but not in TbetaRII knockdown cells. In BEP2D cells, TGF-beta1 treatment effectively inhibited cells' proliferation and induced their apoptosis. Pretreatment with U0126, an inhibitor of ERK1/2, significantly enhanced the TGF-beta1-mediated antiproliferative and apoptosis induction effects in BEP2D cells. These data revealed that TbetaRII and Smad7 play the critical roles in TGF-beta1-mediated activation of ERK; Smad3 and Smad4 can play an indirect role through up-regulating Smad7 expression; and TGF-beta1-induced phosphorylation of ERK may participate in BEP2D cell proliferation and apoptosis regulation.

Inhibition of adenylate cyclase by tetraplatin.

In the investigation of effects of platinum-containing compounds on dopamine (DA)-activated adenylate cyclase system, tetraplatin and cisplatin were found to suppress the increase of enzyme activity by various activators. However, tetraplatin was a much more potent inhibitor than cisplatin, with its I50 values being 1/25, 1/45, and 1/130 that of cisplatin in the presence of DA/Gpp(NH)p, NaF/AlCl3, and forskolin/Gpp(NH)p respectively.

Analgesic activity of anticancer agent suramin.

Suramin exhibited morphine-like analgesic activity in mice. It antagonized both thermal (hot-plate) and acetic acid-evoked writhing responses with ED50 values 1/100 and 1/68, respectively, that of morphine. The suramin- and morphine-induced hot-plate analgesia was suppressed by administration of 0.5 mg/kg naloxone. However, lower doses (5-30 micrograms/kg) of naloxone produced dose-related potentiation or suppression of suramin and morphine analgesia. This potentiation effect may be due to the inhibition of writhing by naloxone itself rather than be a direct antagonism of the morphine effect.

The opioid mechanism of interferon-alpha action.

Rats were trained to discriminate the opioid receptor agonist ethylketocyclazocine (EKC) (0.3 mg/kg body weight, intraperitoneally) from saline. Interferon-alpha (IFN-alpha), when substituted for EKC, elicited a dose-related increase in EKC-like responses. This generalization of EKC responses was blocked by the opioid antagonist naloxone (1 mg/kg). Potentiation of responses to a low dose (0.1 mg/kg) of EKC by IFN-alpha (1 x 10(6) U/kg or 0.22 nmol/kg) was also observed. Data thus indicate the involvement of opioid neurons on the action of IFN-alpha. d-Amphetamine (0.8 mg/kg) was shown to potentiate both EKC (0.1 mg/kg) and IFN-alpha (1 x 10(6) U/kg). The present study confirms our previously proposed opioid-mediated dopaminergic mechanism of IFN-alpha.

Neurochemical basis of interleukin 2-modified discrimination behaviour.

We trained one group of rats to discriminate 0.8 mg/kg intraperitoneal (i.p.) d-amphetamine from 1 ml/kg saline and the other to discriminate 0.3 mg/kg i.p. (+/-)-ethylketocyclazocine (EKC) from saline. Recombinant human interleukin 2 (rIL-2), 2 x 10(6) U/kg (or 8.2 nmol/kg) given i.p. 1 h prior to tests, potentiated responses elicited by 0.4 mg/kg d-amphetamine. This potentiation of d-amphetamine responses was suppressed by the opioid receptor antagonist naloxone (1 mg/kg) when administered i.p. together with IL-2. IL-2 (4 x 10(6) U/kg) alone produced EKC-like responses in the EKC-trained animals. The cytokine also potentiated 0.1 mg/kg EKC responses at 2 x 10(6) U/kg, an action that was suppressed by 1 mg/kg naloxone. Data from the present study show that IL-2 exerts the same neurochemical action as that previously observed with IFN-alpha for both d-amphetamine and EKC discrimination in rats.