FANCD2 is involved in DNA damage repair and maintenance of chromosome stability. The purpose of this study was to investigate the expression of FANCD2 in sporadic breast cancer tissues and its association with clinicopathological features. A total of 162 Chinese women with invasive breast carcinoma who had no family history in first-degree relatives and 12 normal breast tissues were examined. The expression of FANCD2 was detected by immunohistochemical staining based on a tissue microarray technique. SAS system was used to analyze the data. Twenty-one out of the 162 invasive breast cancers (13%) were negative for FANCD2. The mean percentage of FANCD2 positive cells was significantly lower in breast cancers than in controls (P<0.05). FANCD2 expression was significantly inversely associated with histological grade and TNM stage (P<0.05), but not with axillary lymph node status or other conventional prognostic markers such as ER, PR, Her-2 and PCNA (P>0.05). It was suggested that FANCD2 may play a critical role in breast carcinogenesis. It may become a valuable and independent marker for identifying women with sporadic breast cancer and evaluating the prognosis.

OBJECTIVETo investigate the nephrotoxic effects of methyl cantharidimide tablets on urinary protein and enzymes in Beagle dogs.

METHODBeagle dogs were randomly divided into negative control group(blank tablet), methyl cantharidimide tablets group (6.11,12.21, 24.42 mg x kg(-1)), continuously 30 days of oral adminiStration, once a day. The drug and control group were collected and determined fresh urine in 1, 2, 3 and 4 weeks of the administration; Serum urea nitrogen (BUN), creatinine (Crea), total protein (TP) and albumin (ALB) as well as sodium, potassium, chloride electrolyte were determined on 15 and 30 days of the administration; Urine albumin (mAlb), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin( NGAL), N-acetyl-beta-D-glucosaminidase (NAG), clusterin, beta2-microglobulin (beta2-MG), alpha1-microglobulin (alpha1-MG), alanine aminopeptidase( AAP) and im- munoglobulins IgG were tested on 15 and 30 days of the administration.

RESULTCompared with the control group, urine protein and white blood cells was significantly increased in each dose group. On 15 days of the administration, mAlb were higher in each dose group, KIM-1, NGAL, clusterin, NAG and AAP were significantly higher in high-dose group, while the middle and low dose group had no significant difference, as well as blood SCr and BUN no obvious abnormalities. On 30 days, mAlb, KIM-1, clusterin, NAG, AAP were increased in each dose group, appearing dose-effect relationship, beta2-MG and NGAL levels were significantly increased in high-dose group. Contents above indicators were increased with significant dose and time relationship, and serum BUN, Scr were correlated, suggesting that urine mAlb, KIM-1, clusterin, NAG and AAP indicators that can sensitively respond the changes of proteins and enzymes in urine.

CONCLUSIONMethyl cantharidimide tablets has a renal toxicity, urine mAlb, KIM-1, clusterin, NAG and AAP can be used as the early nephrotoxic biomarkers of methyl cantharidimide tablets.

Animals ; Biomarkers ; urine ; Dogs ; Female ; Kidney ; drug effects ; Kidney Diseases ; chemically induced ; Male ; Proteins ; metabolism ; Tablets ; adverse effects ; Urine ; chemistry

Cannabinoid receptors are one of the most expressed G protein-coupled receptors in the central nervous system, which are potential drug targets for inflammation, pain and drug abuse. Cannabinoid receptors are composed of type 1 receptor (CB1R), type 2 receptor (CB2R) and other receptors, of which CB1R plays a vital role in regulating central memory, cognition, and motor function. Therefore, screening CB1R agonists has potential value in treating nervous system diseases. In this study, the intracellular loop 3 (ICL3) domain of CB1R was replaced with a circular-permutated enhanced green fluorescent protein (cpEGFP). After infecting HEK 293T cells with lentivirus particles, we obtained a stable cell line that was overexpressed human CB1R-cpEGFP after puromycin selection. The interaction between receptor agonists and CB1R led to the change of receptor conformation, resulting in de-protonation of the EGFP, and enhancing the fluorescence intensity. Therefore, active CB1R compounds could be verified by measuring the fluorescence intensity. Using CB1R agonist arachidonyl-2′-chloroethylamide (ACEA) as a positive control to evaluate the reliability of this model, studies have shown that ACEA could induce receptor activation and increase fluorescence intensity, while antagonist rimonabant inhibited receptor activation with unchanged fluorescence intensity. In conclusion, this study successfully constructed a fluorescent probe screening model for CB1R agonists.

To study the effect of Tibetan medicine Zuotai on the activity, protein and mRNA expression of CYP1A2 and NAT2, three different doses (1.2, 3.8 and 12 mg x kg(-1)) of Zuotai were administrated orally to rats once a day or once daily for twelve days, separately. Rats were administrated orally caffeine (CF) on the second day after Zuotai administration, and the urine concentration of CF metabolite 5-acetylamino-6-formylamino-3-methyl-uracil (AFMU), 1-methyluric acid (1U), 1-methylxanthine (1X), 1, 7-dimethylxanthine (17U) at 5 h after study drug administration was determined by RP-HPLC. The activity of CYP1A2 and NAT2 was evaluated by the ratio of metabolites (AFMU+1X+1U)/17U and the ratio of AFMU/(AFMU+1X+1U), respectively. The protein and mRNA expression of CYP1A2 and NAT2 were determined by ELISA and RT-PCR method, respectively. After single administration of Zuotai 3.8 mg x kg(-1) and repeated administration of Zuotai 3.8 and 12 mg x kg(-1), the activity of CYP1A2 and NAT2 decreased significantly compared with control group and there was no significant difference between other dose group and control group. The protein expression of CYP1A2 was significant lower than that in control group after repeated administration of Zuotai 12 mg x kg(-1), and the mRNA expression of CYP1A2 decreased significantly compared with that of control group after single administration of Zuotai 3.8 mg x kg(-1) and repeated admistration of Zuotai 12 mg x kg(-1), separately. The protein expression of NAT2 decreased significantly compared with that of control group after single and repeated administration of Zuotai 3.8 mg x kg(-1), respectively, and the mRNA expression of CYP1A2 decreased significantly compared with control group after single administration of Zuotai 3.8 mg x kg(-1). This study found that Tibetan medicine Zuotai had significant effect on the activity, protein and mRNA expression of CYP1A2 and NAT2.
Administration, Oral ; Animals ; Arylamine N-Acetyltransferase ; genetics ; metabolism ; Caffeine ; metabolism ; urine ; Cytochrome P-450 CYP1A2 ; genetics ; metabolism ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Female ; Male ; Medicine, Tibetan Traditional ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Theophylline ; urine ; Uracil ; analogs & derivatives ; urine ; Uric Acid ; analogs & derivatives ; urine ; Xanthines ; urine

The objective of this work was to develop a valuable adsorbent for recovery of platinum by studying the properties of Pt4+ -adsorption with immobilized Citrobacter freudii XP05 biomass. Five methods for immobilization of Citrobacter freudii XP05 biomass were compared. The method with gelatin-alginate sodium as entrapment matrix was considered to be the optimal. Spherical and uniform beads were produced and the SEM micrograph indicated that the cell of strain XP08 were uniformly dispersed within the matrix. The adsorption of Pt4+ by immobilized XP05 biomass was affected with adsorptive time, pH value of the solution, immobilized biomass concentration, Pt4+ initial concentration The adsorption was a rapid process. The optimal pH value for Pt4+ adsorption was 1.5, and its adsorptive capacity increased linearly with increasing Pt4+ initial concentrations in the range of 50 - 250 mg/L. The experimental data could be fitted to Langmuir and Freundlich models of adsorption isotherm. The adsorptive capacity reached 35.2 mg/g under the conditions of 250 Pt4+ mg/L, 2.0 g/L immobilized biomass, pH 1.5 and 30 degrees C for 60 min. 98.7% of Pt4+ adsorbed on immobilized biomass could be desorbed with 0.5 mol HC1/L. The characteristics of dynamic adsorption and desorption of immobilized XP05 biomass in packed-bed reactor were investigated. The saturation uptake was 24.66 mg Pt4+ /g under the conditions of flow rate 1.2 mL/min, pH 1.5, 50 mg Pt4+/L and 1.85 g biomass(dry weight) . Adsorptive efficiency of Pt4 + by the immobilized XP05 biomass was above 78% for 4 cycles of adsorption and desorption. The recovery of platinum from waste platinum catalyst was studied. The adsorptive capacity was 20.94 mg Pt4+/g immobilized biomass under the conditions of 4.0 g/L immobilized XP05 biomass, 117.76 mg Pt4+/L and pH 1.5 for 60 min. The immobilized XP05 biomass is potentially applicable to the recovery of platinum from waste and wastewater containing platinum.
Biomass ; Bioreactors ; microbiology ; Citrobacter ; metabolism ; Microscopy, Electron, Scanning ; Microspheres ; Platinum ; isolation & purification ; metabolism ; Waste Disposal, Fluid ; methods ; Water Pollutants, Chemical ; isolation & purification ; metabolism

To exert pharmacological effects, no matter therapeutic effect or toxic/side effect, it's necessary to achieve enough plasma concentration. Chinese medical compounds, which contain various ingredients, influence the metabolism of some active ingredients through the interaction of ingredients to improve curative effects or reduce toxic/side effects. Pharmacokinetics can be used to explore how Chinese medical compounds influence the in vivo metabolism of some active ingredients to achieve better curative effects.
Drugs, Chinese Herbal ; pharmacokinetics ; pharmacology ; Humans

BACKGROUND: Thoracolumbar fracture is commonly seen in spinal injuries, which causes loss of stability of the spine, as well as spinal cord and nerve compression, even deformity and paralysis. The diagnosis and treatment of thoracolumbar fracture remain controversial.OBJECTIVE: To summarize the mechanism of thoracolumbar fracture based on finite element method, its classification and transpedicular screw fixation.METHODS: The first author retrieved CNKI and PubMed databases for the relevant literature published between January 2000 and December 2016. The keywords were "finite element method, thoracolumbar spine fracture,transpedicular screw fixation" in Chinese and English, respectively.RESULTS AND CONCLUSION: (1) The finite element analysis method can simulate the mechanism of thoracolumbar fracture and provides a reference for the studies on the occurrence, development and treatment of thoracolumbar fracture. (2) The classification of thoracolumbar fracture is beneficial for planning a rational treatment strategy and evaluating prognosis. (3) Compared with the traditional screw fixation, the transpedicular screw fixation holds advantages in biomechanical stability and postoperative correction effect. (4) There are various classifications for thoracolumbar fracture; differences in severity and cartilage injury are difficult to simulate completely. (5) The finite element analysis method shows certain application limitations due to long learning curve and modeling time as well as complicated calculations.

FANCD2 is involved in DNA damage repair and maintenance of chromosome stability.The purpose of this study was to investigate the expression of FANCD2 in sporadic breast cancer tissues and its association with clinicopathological features.A total of 162 Chinese women with invasive breast carcinoma who had no family history in first-degree relatives and 12 normal breast tissues were examined.The expression of FANCD2 was detected by immunohistochemical staining based on a tissue microarray technique.SAS system was used to analyze the data.Twenty-one out of the 162 invasive breast cancers(13%)were negative for FANCD2.The mean percentage of FANCD2 positive cells was significantly lower in breast cancers than in controls(P＜0.05).FANCD2 expression was significantly inversely associated with histological grade and TNM stage(P＜0.05),but not with axillary lymph node status or other conventional prognostic markers such as ER,PR,Her-2 and PCNA(P＞0.05).It was suggested that FANCD2 may play a critical role in breast carcinogenesis.It may become a valuable and independent marker for identifying women with sporadic breast cancer and evaluating the prognosis.

Through our pre-investigation and literature analysis, it was found that rhubarb could be categorized into two types, chrysophanol-type and rhein-type, based on the proportion of the two constituents in the total content of anthraquinones after acid hydrolysis. In this paper, the antimicrobial activities of chrysophanol-type and rhein-type rhubarbs against Staphylococcus aureus were compared with microcalorimetric analysis, in order to illustrate the bioactive differentiability between the two chemotypes. For the aim to display the distinction of chrysophanol and rhein percentage in total anthraquinones, the sampling volume was regulated to make the total anthraquinones equivalent, thus, the antimicrobial difference was only attributed to the difference of chemotypes. The results indicated that the antimicrobial difference between the two chemotypes was confirmable labeled at the biothermokinetic parameters of S. aureus growth affected by the rhubarb samples. The growth rate constant (k1) of the first exponential phase for the growth of S. aureus affected by the rhein-type rhubarb was significantly lower than that of chrysophanol-type (P<0.01), which suggested stronger antimicrobial activity of rhein-type rhubarb than that of chrysophanol-type. However, the antimicrobial activities of rhein-type rhubarbs were not positively correlated to the contents of rhein. It suggested that the antimicrobial activity of rhubarb might be related to some unknown components which were of same accumulating pattern of rhein. The findings in present study provided some experimental evidence on categorizing rhubarb into two chemotypes through the difference of antimicrobial activity on S. aureus by microcalorimetric analysis and, further, offered references to revision of the commercial specification of rhubarb from chemical view.
Anthraquinones ; isolation & purification ; pharmacology ; Anti-Infective Agents ; isolation & purification ; pharmacology ; Calorimetry ; Plants, Medicinal ; chemistry ; Rheum ; chemistry ; Staphylococcus aureus ; drug effects ; growth & development

BACKGROUNDTumor necrosis factor-induced protein 3 (TNFAIP3) gene has been shown important in cardiac remodeling. The aim of the present study was to investigate whether the variants of TNFAIP3 gene are associated with left ventricular hypertrophy (LVH) in hypertensive patients.

METHODSFour representatives of all the other single nucleotide polymorphisms (SNPs) in TNFAIP3 gene were tested for association with hypertrophy in two independent hypertensive populations (n = 2120 and n = 324).

RESULTSWe found that only the tag SNP (rs5029939) was consistently lower in the hypertensives with cardiac hypertrophy than in those without cardiac hypertrophy in the two study populations, indicating a protective effect on LVH (odds ratio (OR) (95% confidence interval (CI)) 0.58 (0.358 - 0.863), P = 0.035; OR (95%CI) = 0.477 (0.225 - 0.815), P < 0.05, respectively). Multiple regression analyses confirmed that the patients with G allele of rs5029939 had less thickness in inter-ventricular septum, left ventricular posterior wall, relative wall thickness and left ventricular mass index than did those with CC allele in the hypertensive patients in both study populations (all P < 0.01).

CONCLUSIONThese findings indicate that the SNP (rs5029939) in the TNFAIP3 gene may serve as a novel protective genetic marker for the development of LVH in patients with hypertension.

Adult ; Aged ; Cross-Sectional Studies ; DNA-Binding Proteins ; Echocardiography ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hypertension ; genetics ; Hypertrophy, Left Ventricular ; genetics ; Intracellular Signaling Peptides and Proteins ; genetics ; Male ; Middle Aged ; Nuclear Proteins ; genetics ; Phenotype ; Polymorphism, Single Nucleotide ; genetics ; Tumor Necrosis Factor alpha-Induced Protein 3