The anticancer effects of wogonin on murine sarcoma S180 both in vitro and in vivo were investigated, and its pro-apoptotic molecular mechanism was further studied. Wogonin treatment resulted in ...significant inhibition of S180 cells in a concentration-dependent manner detected by MTT assay. The IC50 value for 48 h was (7.37±1.53)×10−5 M. Typical morphological changes and apoptosis bleb phenomenon in S180 cells exposed to wogonin were distinctly observed by the inverted light microscope and the fluorescence microscope, respectively. According to protocols of transplanted tumor research,1) mice were transplanted with tumor cells S180. The weight of tumor and the peripheral leucocyte count were observed after the treatment of wogonin. The significant suppression of tumor growth was observed, and the peripheral leucocyte count of S180-bearing mice remained no significant changes compared with control group. After the treatment of 40 mg/kg wogonin, the inhibitory rate of tumor weight was 53.01%. Additional DNA fragmentation assay showed that wogonin induced apoptosis on murine sarcoma S180 tissue. RT-PCR results indicated that the increasing mRNA levels of bax and p53 and the decreasing mRNA level of bcl-2 were induced by wogonin. Western-blot assay showed that the increasing protein level of bax and the decreasing protein level of bcl-2 were induced by wogonin. Collectively, wogonin could induce apoptosis in murine sarcoma S180 thereby inhibiting the tumor growth both in vitro and in vivo. The pro-apoptotic effects might be related to the improvement of mRNA level of p53, the improvement of mRNA and protein levels of bax, and the reduction of mRNA and protein levels of bcl-2.
Background Delay in seeking medical care in patients with acute myocardial infarction （AMI） is receiving increasing attention. This study aimed to examine the association between expected symptoms ...and experienced symptoms of AMI and its effects on care-seeking behaviors of patients with AMI. Methods Between November 1, 2005 and December 31, 2006, a cross-sectional and multicenter survey was conducted in 19 hospitals in Beijing and included 799 patients with ST-elevation myocardial infarction （STEMI） admitted within 24 hours after onset of symptoms. Data were collected by structured interviews and medical record review. Results The median （25%, 75%） prehospital delay was 140 （75, 300） minutes. Only 264 （33.0%） arrived at the hospital by ambulance. The most common symptoms expected by patients with STEMI were central or left chest pain （71.4%）, radiating arm or shoulder pain （68.7%）, shortness of breath or dyspnea （65.5%）, and loss of consciousness （52.1%）. The most common symptoms experienced were central or left chest pain （82.1%）, sweats （71.8%）, shortness of breath or dyspnea （43.7%）, nausea or vomiting （32.3%）, and radiating pain （29.4%）. A mismatch between symptoms experienced and those expected occurred in 41.8% of patients. Patients who interpreted their symptoms as noncardiac in origin were more likely to arrive at the hospital by self-transport （86.5% vs. 52.9%, P 〈0.001） and had longer prehospital delays （medians, 180 vs. 120 minutes, P 〈0.001） compared to those who interpreted their symptoms as cardiac in origin. Conclusions Symptom interpretation influenced the care-seeking behaviors of patients with STEMI in Beijing. A mismatch between expectation and actual symptoms was associated with longer prehospital delay and decreased use of emerqency medical service （EMS）.
Objective: We applied a comparative functional genomics approach to evaluate whether diet‐induced obese (DIO) rats serve as an effective obesity model.
Methods and Procedures: Gene‐expression ...profiles of epididymal fat from DIO and lean rats were generated using microarrays and compared with the published array data of obese and non‐obese human subcutaneous adipocytes.
Results: Caloric intake and fuel efficiency were significantly higher in DIO rats, which resulted in increased body weight and adiposity. Circulating glucose, cholesterol, triglyceride, insulin, and leptin levels in DIO rats were significantly higher than those in the lean controls. DIO rats also exhibited impaired insulin sensitivity. A direct comparison of gene‐expression profiles from DIO and lean rats and those from obese and non‐obese humans revealed that global gene‐expression patterns in DIO rat fat resemble those of obese human adipocytes. Differentially expressed genes between obese and non‐obese subjects in both human and rat studies were identified and associated with biological pathways by mapping genes to Gene Ontology (GO) categories. Immune response–related genes and angiogenesis‐related genes exhibited significant upregulation in both obese humans and DIO rats when compared with non‐obese controls. However, genes in fatty acid metabolism and oxidation exhibited a broad downregulation only in obese human adipocytes but not in DIO rat epididymal fat.
Discussion: Our study based on gene‐expression profiling suggested that DIO rats in general represent an appropriate obesity model. However, the discrepancies in gene‐expression alterations between DIO rats and obese humans, particularly in the metabolic pathways, may explain the limitations of using DIO rodent models in obesity research and drug discovery.
The search for new organic semiconductors with enhanced charge transport properties and self-organizing abilities plays a pivotal role in the development of new applications in the emerging field of ...organic electronics. We have synthesized two series of discotic mesogenic materials derived from hexasubstituted triphenylene, including (i) 1-aryl-2,3,6,7,10,11-hexakis(pentyloxy)triphenylenes (14 new compounds) by a Suzuki cross-coupling reaction between the appropriate 1-bromotriphenylene precursor and various arylboronic acids and (ii) unsymmetrical facial dibenzo fg , op tetracene discotic molecules (11 new compounds) by an FeCl 3 -oxidized cyclodehydrogenation reaction of the former. The mesomorphism has been investigated by polarizing optical microscopy, differential scanning microscopy, and small-angle X-ray scattering. Most aryl-substituted triphenylene derivatives exhibit a single hexagonal columnar mesophase, enantiotropic over small temperature ranges or monotropic, with this low stability being likely attributed to the free-rotating bulky side-on arene group that disrupts a perfect stacking. The corresponding more rigid and flat dibenzo fg , op tetracene derivatives also self-organize into a hexagonal columnar mesophase, but with a larger mesophase stability than their parents, and occurring slightly above room temperature. The UV/vis absorption and fluorescence emission spectra have been measured. Tetracenes show stronger photoluminescence than aryltriphenylene in solution, while the reversed is observed in thin films, where a strong excimer emission for one of the polar 1-aryltriphenylenes is observed. The charge carrier mobility of two representative discogens has been measured by the time-of-flight photocurrent technique. The results show that the discogen with a lateral nucleus dipole displays a hole mobility of 10 −4 cm 2 V −1 s −1 in the mesophase, while the non-polar compound exhibits a hole mobility of 10 −2 cm 2 V −1 s −1 in its metastable-induced ordered phase. The charge carrier mobility is discussed as a function of the supramolecular organization.
Knoevenagel condensations of
α
,
β
-unsaturated aldehydes and 1,3-dicarbonyl compounds were catalyzed by primary natural amino acid L-lysine. The reactions were carried out at room temperature in ...dimethylsulfoxide. It provides a facile entry to a wide variety of
α
,
β
,
γ
,
δ
-unsaturated dicarbonyl compounds.
Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.
Highlights • Rhesus macaques are an effective animal model for bacterial vaginosis • Sucrose gel reduces the vaginal pH in rhesus macaques • Sucrose gel selectively promotes growth of Lactobacillus ...species • The proportion of Gram-negative bacteria is reduced with sucrose gel application • Sucrose gel provides a non-antibiotic alternative for treating bacterial vaginosis
Decitabine (DAC) is commonly used for the treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Previous studies have indicated DAC sequentially combined with idarubicin was ...an effective treatment for myeloid neoplasms. Therefore, a clinical study was conducted of the sequential combination of DAC followed by low-dose idarubicin/cytarabine in high-risk myeloid neoplasms. A total of 30 patients with a diagnosis of high-risk MDS, AML evolving from MDS or relapsed/refractory AML were enrolled in the study. DAC was administered 20 mg/m(2) daily for 3 consecutive days. Idarubicin (3 mg/m(2)/day) was administered 24 h after the last administration of DAC for 5-7 consecutive days, combined with cytarabine (30 mg/m(2)/day) for 7-14 days. The overall complete remission rate was 66.67%. The results demonstrate that epigenetic priming with decitabine followed by low-dose idarubicin/ytarabine has an increased anti-leukemia effect compared to traditional chemotherapy in high-risk myeloid neoplasms.
Acute myeloid leukemia (AML) is the second most common form of leukemia in children. Aberrant DNA methylation patterns are a characteristic feature in various tumors, including AML. Metallothionein ...III (MT3) is a tumor suppresser reported to show promoter hypermethylated in various cancers. However, the expression and molecular function of MT3 in pediatric AML is unclear.
Eleven human leukemia cell lines and 41 pediatric AML samples and 20 NBM/ITP (Norma bone marrow/Idiopathic thrombocytopenic purpura) control samples were analyzed. Transcription levels of MT3 were evaluated by semi-quantitative and real-time PCR. MT3 methylation status was determined by methylation specific PCR (MSP) and bisulfite genomic sequencing (BSG). The molecular mechanism of MT3 was investigated by apoptosis assays and PCR array analysis.
The MT3 promoter was hypermethylated in leukemia cell lines. More CpG's methylated of MT3 was observed 39.0% pediatric AML samples compared to 10.0% NBM controls. Transcription of MT3 was also significantly decreased in AML samples compared to NBM/ITP controls (P < 0.001); patients with methylated MT3 exhibited lower levels of MT3 expression compared to those with unmethylated MT3 (P = 0.049). After transfection with MT3 lentivirus, proliferation was significantly inhibited in AML cells in a dose-dependent manner (P < 0.05). Annexin V assay showed that apoptosis was significantly upregulated MT3-overexpressing AML cells compared to controls. Real-time PCR array analysis revealed 34 dysregulated genes that may be implicated in MT3 overexpression and apoptosis in AML, including FOXO1.
MT3 may be a putative tumor suppressor gene in pediatric AML. Epigenetic inactivation of MT3 via promoter hypermethylation was observed in both AML cell lines and pediatric AML samples. Overexpression of MT3 may inhibit proliferation and induce apoptosis in AML cells. FOXO1 was dysregulated in MT3-overexpressing cells, offering an insight into the mechanism of MT3-induced apoptosis. However, further research is required to determine the underlying molecular details.
Objective Evidence suggests that type 2 diabetes （T2DM） is associated with an increased risk of dementia and that glucose variability is an independent risk factor for diabetic complications. This ...study investigated the relationship between glucose excursion and cognitive function in aged T2DM patients. Methods A total of 248 aged T2DM patients wore a continuous glucose monitoring system （CGMS） for 3 days in order to evaluate glucose excursion, including mean amplitude of glycemic excursions （MAGE） and mean of daily difference （MODD）. All subjects were evaluated with a number of accepted cognitive function tests, including the mini-mental status examination （MMSE）. The relationship between MAGE and MODD and performance on these cognitive tests was assessed. Results The MAGE and MMSE score were negatively correlated, likewise with the correlation between MODD and MMSE. Liner multivariate regression analysis showed that MAGE and MODD were also negatively related to MMSE independent of age, sex, glycemic control, hypertension, smoking, or coronary heart disease history. Conclusion Glucose excursion is related to cognitive function in aged T2DM patients. Elevated glucose excursion decreased the MMSE score, which reflects general cognitive function. Thus, therapy aimed at controlling glucose excursion may be beneficial for maintaining cognitive function in aged T2DM patients.
The effects of Sm additions （0, 0.5 wt.%, 1.0 wt.%and 1.5 wt.%） on the eutectic Si and β-Al5FeSi phases of ADC12 as-cast alloys were studied by optical microscopy （OM）, scanning electron microscopy ...（SEM） and differential thermal analysis （DTA）. The experimental results showed that Sm was an effective modifying agent for the eutectic Si of ADC12 alloy, when 1.0 wt.%-1.5 wt.%Sm was added to the alloy, the coarse acicular eutectic Si was modified into fine particle or short rod structure. Moreover, the appropriate addition of Sm （about 1.0 wt.%） had marked effects on shortening the length of needle-likeβ-Al5FeSi phase. Whereas, Sm was less effective on modifying the needle-likeβ-iron to the Chinese script or sphericalα-iron phase. The modification mecha-nism was also discussed.
PDF
