Congenital eye illnesses are caused by congenital ocular malformations and are a primary cause of poor visual acuity and blindness in infants. Early diagnosis and treatment of congenital eye illnesses are of great significance for affected infants, their families, and even society as a whole. This study describes the current situation for prenatal and infant screening for congenital eye diseases and briefly summarizes novel progress in the treatment of the five most common eye diseases (congenital dacryocystitis, congenital cataract, retinopathy of prematurity, congenital glaucoma and retinoblastoma). Current programs are now aimed at improvements in the prevention and treatment of congenital eye diseases in China.Read more
Two C₂₁- and C₂₂-terpenoids, salviprzols A (1) and B (2), together with 24 known compounds including 17 diterpenoids (3-19), a triterpenoid (20), and 6 phenolic derivatives (21-26), were isolated from the roots of Salvia przewalskii Maxim. Salviprzols A and B represented a new subtype of C₂₃-terpenoids featured by an additional 2-oxopropyl moiety at C-12 and a rare γ-hydroxyl-α-methyl-α,β-unsaturated-γ-lactone ring system. Their structures were elucidated by extensive spectroscopic analyses, and the structure of 2 was confirmed by a single-crystal X-ray diffraction crystallography. The cytotoxic activities of the new isolates were tested. A plausible biosynthetic pathway for 1 and 2 was also proposed.Read more
To isolate and culture cardiac stem cells (CSCs) in vitro and evaluate their potential of differentiation into functional cardiac myocytes.
Myocardial tissues obtained from neonatal SD rats were cut into pieces of 0.5-1.0 mm(3), and digested twice for 5 min at 37 degrees C; with 0.2% trypsin and 0.1% collagenase II. The remaining tissues were cultured in complete explant culture medium (CEM) at 37 degrees C; in the presence of 5% CO(2). About a week later, a layer of fibroblast-like cells was generated from the adherent explants. These cells were passaged and seeded at about 1x10(6) cells/ml in poly-D-lysine-coated multi-well plates in cardiosphere-growing medium. When beating of the cultured cells was observed (at week 2), flow cytometry and immunohistochemistry were performed for identification of the primary and passaged cells.
The primary cells were successfully cultured from the digested myocardial tissue, and flow cytometry demonstrated the phenotype of c-kit(+)CD31(+)CD34(-)CD45(-)CTnT(-). After cell passage for about two weeks, single beating cells and cell clusters with synchronized contraction were seen microscopically, and their phenotype was converted to c-kit(+)CD31(-)CD34(-)CD45(-) CTnT(+). Immunohistochemistry staining identified CTnT expression in the passaged cells but not in the primary cells.
A cell population with the phenotype c-kit(+)CD31(+)CD34(-)CD45(-)CTnT(-) has been obtained from neonatal SD rat heart, which possesses the potential to differentiate in vitro into beating cardiac myocytes and express CTnT protein.Read more
A series of novel 1-((indol-3-yl)methyl)-1H-imidazolium salts were prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the 5,6-dimethyl-benzimidazole ring, and substitution of the imidazolyl-3-position with a naphthylacyl or 4-bromophenacyl group, were vital for modulating inhibitory activity of cell growth. In particular, 1-((N-Boc-indol-3-yl)methyl)-3-(2-naphthylacyl)-1H-5,6-dimethyl-benzimidazolium bromide was found to be the most potent derivative and more selective against myeloid liver carcinoma (SMMC-7721), lung carcinoma (A549) and breast carcinoma (MCF-7), with IC50 values 1.9-fold, 1.7-fold and 4.8-fold lower than DDP. This compound can induce significant cell apoptosis in SMMC-7721 cells.Read more
Two compounds belonging to a new group of diterpene alkaloids, kaurines A and B (1 and 2), and an alkaloid bearing a succinimide moiety (3) were obtained from Isodon rubescens. Their structures and absolute configurations were determined by spectroscopy and quantum-chemical computational (13)C NMR and ECD data analysis. These alkaloids differ from known diterpene alkaloids and diterpenoids and are presumably biosynthesized from ent-kaurane diterpenoids.Read more
PXR, CAR and PPAR, widely distributed in the body, are important members of the nuclear receptors (NRs) family. The activities and gene expressions of drug-metabolizing enzymes (DMEs) and transporters can be regulated by the activation of NRs, which effect the drug disposition. Multidrug resistance (MDR) is the leading cause of failure in cancer therapy. NRs, including PXR, CAR and PPAR, were shown to regulate the expressions of DMEs and transporters involved in the drug metabolism and clearance, suggesting that the modulation of NRs can be considered as a new target to overcome MDR. This review described the research progress of NR family members PXR, CAR, PPAR and their transcriptional activation mechanism, the regulation of DMEs and transporters by NRs, which may provide a valuable reference for clinical medication and overcome of MDR.Read more
FB2 is a promising Abl/Src dual tyrosine kinase inhibitor which is designed to overcome imatinib resistance. The present study aims to investigate the role of P-glycoprotein (P-gp) in intestinal absorption of FB2 with an in vitro Caco-2 and MDCK-MDR1 cell model, single-pass intestinal perfusion model and in vivo pharmacokinetics with a selective inhibitor in rats. The results from Caco-2 cells indicated that P(appB-A) of FB2 and its metabolites (FB7 and FB10) were much higher than P(appA-B), and the efflux ratio (P(appB-A)/P(appA-B)) of FB2, FB7 and FB10 were decreased with P-gp inhibitor LSN335984; FB2 was further confirmed to be the substrate of P-gp in MDCK-MDR1 cells. In addition, P(blood) of FB2 and the cumulative amount of metabolites in mesenteric blood were elevated in a concentration-dependent manner in rat intestinal perfusion, while both of them were remarkably increased when P-gp inhibitor was added. The F(oral) of FB2 was increased to 24.52% when orally coadministrated with verapamil (25 mg/kg), which was significantly higher than that (5.7%) by FB2 (18 mg/kg) alone in rats. The AUC and Cmax of FB2 metabolites (FB7 and FB10) were also increased in the presence of verapamil. In conclusion, the low bioavailability of FB2 is believed to be partially due to the P-gp mediated active efflux and first-pass metabolism in the rat intestine.Read more
To evaluate the efficacy and safety of middle-dose cyclophosphamide plus methylprednisolone for myasthenia gravis (MG) patients in crisis.
For this prospective, open, parallel, randomized controlled trial, we recruited a total of 156 MG patients in crisis from January 1999 to October 2011 at Department of Neurology, First Affiliated Hospital, Sun Yat-sen University. They were divided into two groups of cyclophosphamide and control (n = 78 each). In the cyclophosphamide group, each received methylprednisolone 500 mg/d for 3 days, then tapered to 250 mg/d and tapered half every 3 days until 62.5 mg/d. Afterward an oral dose of prednisone was prescribed at 30 mg/d until the end of the trial. At the same time, an intravenous injection of cyclophosphamide was offered at 0.4 g/d for 3 days and then 0.4 g/d every 3 days. In the control group, each received methylprednisolone alone. And the efficacies were assessed by absolute and relative MG scores.
(1) There were 54 (69.2%) patients off-ventilation in 3 days in the cyclophosphamide group versus 36 (46.2%) patients in 8 - 14 days in the control group. Notable statistical significance existed between two groups (P = 0.000). (2) More than half of the patients in cyclophosphamide group with extremity weakness (n = 44, 56%) and dysphagia (n = 47, 60.3%) significantly improved in 10 - 14 days versus 28 days in the control group. Notable statistical significance existed between two groups (P = 0.000). (3) In the cyclophosphamide group, dyspnea disappeared in 54 (69.2%) patients when the dose reached 1.2 g. The recovery of dysphagia (n = 47, 60.3%) and extremity weakness (n = 44, 56.4%) occurred in more than half of the patients when the dose reached 2.8 g. Notable statistical significance existed among three groups (P = 0.000). (4) During the treatment period, there were 17 cases (21.8%) with pulmonary infection in the cyclophosphamide group versus 53 cases (67.9%) in the control group. Notable statistical significance existed between two groups (P = 0.000). (5) Brief and minor side effects appeared in the patients of the cyclophosphamide group.
(1) The combined treatment of middle-dose cyclophosphamide and methylprednisolone for MG patients in crisis is both effective and safe. (2) When combined with methylprednisolone, 90% of patients with MG crisis are successfully off-ventilation when the dose of cyclophosphamide reaches 1.6 g.Read more
Most residents in New York City (NYC) do not consume sufficient fruits and vegetables every day. Difficulties with access and high prices of fruits and vegetables in some neighborhoods contribute to different consumption patterns across NYC neighborhoods. We developed an agent-based model (ABM) to predict dietary behaviors of individuals at the borough and neighborhood levels. Model parameters were estimated from the 2014 NYC Community Health Survey, United States Census data, and the literature. We simulated six hypothetical interventions designed to improve access and reduce the price of fruits and vegetables. We found that all interventions would lead to increases in fruit and vegetable consumption but the results vary substantially across boroughs and neighborhoods. For example, a 10% increase in the number of fruit/vegetable vendors combined with a 10% decrease in the prices of fruits and vegetables would lead to a median increase of 2.28% (range: 0.65%-4.92%) in the consumption of fruits and vegetables, depending on neighborhood. We also found that the impact of increasing the number of vendors on fruit/vegetable consumption is more pronounced in unhealthier local food environments while the impact of reducing prices on fruits/vegetable consumption is more pronounced in neighborhoods with low levels of education. An agent-based model of dietary behaviors that takes into account neighborhood context has the potential to inform how fruit/vegetable access and pricing strategies may specifically work in tandem to increase the consumption of fruits and vegetables at the local level.Read more