Epidemiologic studies have examined the association between fruit and vegetable (F&V) consumption and the risk of cancer. Several cancer-preventive mechanisms have been proposed, such as antioxidant properties and modulation of biotransformation enzyme activities; both may be associated with reducing DNA damage and hence the mutation rate. We investigated, in a randomized, controlled, crossover feeding trial, the effect of 10 servings/day of botanically defined F&V for 2 wk on endogenous DNA damage; resistance to γ-irradiation damage; and DNA repair capacity in lymphocytes, measured by the Comet assay. We also explored the association between the UGT1A1*28 polymorphism and serum bilirubin concentrations and DNA damage and repair measures. Healthy men (n = 11) and women (n = 17), age 20 to 40 yr, provided blood samples at the end of each feeding period. Overall, F&V did not affect DNA damage and repair measures in lymphocytes. The number of UGT1A1*28 alleles was inversely associated with sensitivity to γ-irradiation exposure and DNA repair capacity, but a biological mechanism to explain this association is unclear. A larger sample size is needed to investigate the association between bilirubin concentrations and endogenous DNA damage. With inconsistent findings in the literature, additional dietary intervention studies on the effect of F&V on DNA damage and repair are needed.
The hydrological cycle is an important way of transportation and reallocation of reactive nitrogen (N) in forest ecosystems. However, under a high level of atmospheric N deposition, the N distribution and cycling through water flows in forest ecosystems especially in bamboo ecosystems are not well understood.
In order to investigate N fluxes through water flows in a Pleioblastus amarus bamboo forest, event rainfall/snowfall (precipitation, PP), throughfall (TF), stemflow (SF), surface runoff (SR), forest floor leachate (FFL), soil water at the depth of 40 cm (SW1) and 100 cm (SW2) were collected and measured through the whole year of 2009. Nitrogen distribution in different pools in this ecosystem was also measured. Mean N pools in vegetation and soil (0–1 m) were 351.7 and 7752.8 kg ha−1. Open field nitrogen deposition at the study site was 113.8 kg N ha−1 yr−1, which was one of the highest in the world. N-NH4+, N-NO3− and dissolved organic N (DON) accounted for 54%, 22% and 24% of total wet N deposition. Net canopy accumulated of N occurred with N-NO3− and DON but not N-NH4+. The flux of total dissolved N (TDN) to the forest floor was greater than that in open field precipitation by 17.7 kg N ha−1 yr−1, due to capture of dry and cloudwater deposition net of canopy uptake. There were significant negative exponential relationships between monthly water flow depths and monthly mean TDN concentrations in PP, TF, SR, FFL and SW1.
The open field nitrogen deposition through precipitation is very high over the world, which is the main way of reactive N input in this bamboo ecosystem. The water exchange and N consume mainly occurred in the litter floor layer and topsoil layer, where most of fine roots of bamboo distributed.
The role of the endogenous secretory receptor for advanced glycation end products (esRAGE) in depression of diabetes patients and its clinical significance are unclear. This study investigated the role of serum esRAGE in patients with type 2 diabetes mellitus with depression in the Chinese population.
Patients and Methods
One hundred nineteen hospitalized patients with type 2 diabetes were recruited at Fujian Provincial Hospital (Fuzhou, China) from February 2010 to January 2011. All selected subjects were assessed with the Hamilton Rating Scale for Depression (HAMD). Among them, 71 patients with both type 2 diabetes and depression were included. All selected subjects were examined for the following: esRAGE concentration, glycosylated hemoglobin (HbA1c), blood lipids, C-reactive protein, trace of albumin in urine, and carotid artery intima-media thickness (IMT). Association between serum esRAGE levels and risk of type 2 diabetes mellitus with depression was also analyzed.
There were statistically significant differences in gender, age, body mass index, waist circumference, and treatment methods between the group with depression and the group without depression (P<0.05). Multiple linear regression analysis showed that HAMD scores were negatively correlated with esRAGE levels (standard regression coefficient −0.270, P<0.01). HAMD-17 scores were positively correlated with IMT (standard regression coefficient 0.183, P<0.05) and with HbA1c (standard regression coefficient 0.314, P<0.01).
Female gender, younger age, obesity, poor glycemic control, complications, and insulin therapy are all risk factors of type 2 diabetes mellitus with combined depression in the Chinese population. Inflammation and atherosclerosis play an important role in the pathogenesis of depression. esRAGE is a protective factor of depression among patients who have type 2 diabetes.
Picria fel-terrae is a traditional Chinese medicine.
Materials and Methods:
A new approach to the search for acetylcholinesterase (AChE) inhibitors from Picria fel-terrae is presented.
Bioassay- and LC-MS-guided fractionation of the ethyl acetate extract was from traditional Chinese medicine P.fel-terrae. Following primary extraction, the ethyl acetate extracts fraction of P.fel-terrae showed strong AChE inhibitory activities. So the sample was separated using highperformance liquid chromatography (HPLC). The effluent was split towards two identical 96-well fraction collectors, and the presence of the biologically interesting portion and chromatographic fractions could be readily detected by analyzing selected ion chromatograms through an electrophoresis-electrospray ionization mass spectrometry (ESIMS) system for accurate mass measurement. One 96-well plate was used for a bioassay (AChE-inhibitory assay) and detected the bioactivity and position of the relevant peak in the chromatogram. The positive well in the second 96-well plate was used for identification by LC-(+) ESIMS.
As abovementioned, the AChE inhibitory constituents from P.fel-terrae by LC-bioassay-ESIMS were rapid identified. Liquid chromatography/ mass spectrometry (LC-MS) screening detected the presence of six active compounds, identified as picfeltarraenin IA (1), picfeltarraenin IB (2), picfeltarraenin IV (3), picfeltarraenin X (4), picfeltarraenin XI (5), and one unknown compound. The structures were further determined by 13C NMR. The six compounds expressed stronger AChE inhibition than the known AChE inhibitorTacrine. Above all, the value of this LC-bioassay-ESIMS methodology is highlighted by the finding and structure elucidation of the active constituents from many other structural families of natural products.
Acetylcholinesterase inhibitory activity; LC-bioassay-ESIMS; Picriafel-terrae
Aberrant sensitivity of incentive neurocircuitry to nondrug rewards has been suggested as either a risk factor for or consequence of drug addiction. Using functional magnetic resonance imaging, we tested whether alcohol-dependent patients (ADP: n = 29) showed altered recruitment of ventral striatal (VS) incentive neurocircuitry compared to controls (n = 23) by: 1) cues to respond for monetary rewards, 2) post-response anticipation of rewards, or 3) delivery of rewards. Using an instrumental task with two-stage presentation of reward-predictive information, subjects saw cues signaling opportunities to win $0, $1, or $10 for responding to a target. Following this response, subjects were notified whether their success would be indicated by a lexical notification (“Hit?”) or by delivery of a monetary reward (“Win?”). After a variable interval, subjects then viewed the trial outcome. We found no significant group differences in voxelwise activation by task contrasts, or in signal change extracted from VS. Both ADP and controls showed significant VS and other limbic recruitment by pre-response reward anticipation. In addition, controls also showed VS recruitment by post-response reward-anticipation, and ADP had appreciable subthreshold VS activation. Both groups also showed similar mesolimbic responses to reward deliveries. Across all subjects, a questionnaire measure of “hot” impulsivity correlated with VS recruitment by post-response anticipation of low rewards and with VS recruitment by delivery of low rewards. These findings indicate that incentive-motivational processing of nondrug rewards is substantially maintained in recovering alcoholics, and that reward-elicited VS recruitment correlates more with individual differences in trait impulsivity irrespective of addiction.
Reward; Impulsivity; Nucleus accumbens; Ventral Striatum; Alcoholism; Substance use disorder; Instrumental behavior
This review is to analyze the role of National Natural Science Foundation of China (NSFC) on the development of basic research of Parkinson’s disease from 1990 to 2012. Data on the total number of projects and funding of NSFC allocated to Parkinson’s disease, as well as hotspots in western countries, papers published, awards, personnel training, subject construction were collected, and the role of NSFC on other sources of funding was evaluated. Over the past 23 years, a full range of continuous funding from NSFC has led to fruitful results and a strong impetus to the progress of basic research of Parkinson’s disease.
Nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease, is increased worldwide in parallel with the obesity epidemic. Our previous studies have showed that the extract of I. hainanensis (EIH) can prevent NAFLD in rat fed with high-fat diet. In this work, we aimed to find biomarkers of NAFLD and investigate the therapeutic effects of EIH. NAFLD model was induced in male Sprague-Dawley rats by high-fat diet. The NAFLD rats were administered EIH orally (250 mg/kg) for two weeks. After the experimental period, samples of 24 h urine were collected and analyzed by ultraperformance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC-Q-TOF). Orthogonal partial least squares analysis (OPLSs) models were built to find biomarkers of NAFLD and investigate the therapeutic effects of EIH. 22 metabolites, which are distributed in several metabolic pathways, were identified as potential biomarkers of NAFLD. Taking these biomarkers as screening indexes, EIH could reverse the pathological process of NAFLD through regulating the disturbed pathway of metabolism. The metabolomic results not only supply a systematic view of the development and progression of NAFLD but also provide a theoretical basis for the prevention or treatment of NAFLD.
Androgenetic alopecia (AGA) is a well-characterized type of progressive hair loss commonly seen in men, with different prevalences in different ethnic populations. It is generally considered to be a polygenic heritable trait. Several susceptibility genes/loci, such as AR/EDA2R, HDAC9 and 20p11, have been identified as being involved in its development in European populations. In this study, we aim to validate whether these loci are also associated with AGA in the Chinese Han population.
We genotyped 16 previously reported single nucleotide polymorphisms (SNPs) with 445 AGA cases and 546 healthy controls using the Sequenom iPlex platform. The trend test was used to evaluate the association between these loci and AGA in the Chinese Han population. Conservatively accounting for multiple testing by the Bonferroni correction, the threshold for statistical significance was P ≤3.13×10−3.
We identified that 5 SNPs at 20p11 were significantly associated with AGA in the Chinese Han population (1.84×10−11≤P≤2.10×10−6).
This study validated, for the first time, that 20p11 also confers risk for AGA in the Chinese Han population and implicated the potential common genetic factors for AGA shared by both Chinese and European populations.
Though multiple single nucleotide polymorphisms (SNPs) associated with type 2 diabetes have been identified, the genetic bases of isolated fasting hyperglycaemia (IFH) and isolated postprandial hyperglycaemia (IPH) were still unclear. In present study, we aimed to investigate the association of genome-wide association study-validated genetic variants and IFH or IPH in Han Chinese.
We genotyped 27 validated SNPs in 6,663 unrelated individuals comprising 341 IFH, 865 IPH, 1,203 combined fasting hyperglycaemia and postprandial hyperglycaemia, and 4,254 normal glycaemic subjects of Han ancestry. The distributions of genotype frequencies of FTO, CDKAL1 and GCKR were significant different between individuals with IFH and those with IPH (SNP(ptrend): rs8050136(0.0024), rs9939609(0.0049), rs7756992(0.0122), rs780094(0.0037)). Risk allele of FTO specifically increased the risk of IFH (rs8050136: OR 1.403 [95% CI 1.125–1.750], p = 0.0027; rs9939609: 1.398 [1.120–1.744], p = 0.0030). G allele of CDKAL1 specifically increased the risk of IPH (1.217 [1.092–1.355], p = 0.0004). G allele of GCKR increased the risk of IFH (1.167 [0.999–1.362], p = 0.0513), but decreased the risk of IPH (0.891 [0.801–0.991], p = 0.0331). In addition, TCF7L2 and KCNQ1 increased the risk of both IFH and IPH. When combined, each additional risk allele associated with IFH increased the risk for IFH by 1.246-fold (p<0.0001), while each additional risk allele associated with IPH increased the risk for IPH by 1.190-fold (p<0.0001).
Our results indicate that genotype distributions of variants from FTO, GCKR, CDKAL1 were different between IPH and IFH in Han Chinese. Variants of genes modulating insulin sensitivity (FTO, GCKR) contributed to the risk of IFH, while variants of genes related to beta cell function (CDKAL1) increase the risk of IPH.
Microglia are regarded as macrophages in the central nervous system (CNS) and play an important role in neuroinflammation in the CNS. Microglial activation has been strongly implicated in neurodegeneration in the brain. Increasing evidence also suggests an important role of spinal cord microglia in the genesis of persistent pain, by releasing the proinflammatory cytokines tumor necrosis factor-alpha (TNFα), Interleukine-1beta (IL-1β), and brain derived neurotrophic factor (BDNF). In this review, we discuss the recent findings illustrating the importance of microglial mediators in regulating synaptic plasticity of the excitatory and inhibitory pain circuits in the spinal cord, leading to enhanced pain states. Insights into microglial-neuronal interactions in the spinal cord dorsal horn will not only further our understanding of neural plasticity but may also lead to novel therapeutics for chronic pain management.
The Watson-Crick like iGiC pair, with the amino and carbonyl groups transposed relative to the Watson-Crick GC pair, provides an expanded alphabet for understanding interactions that shape nucleic acid structure. Here, thermodynamic stabilities of tandem GA pairs flanked by iGiC pairs are reported along with the NMR structures of the the RNA self-complementary duplexes (GCiGGAiCGCA)2 and (GGiCGAiGCCA)2. A sheared GA pairing forms in (GCiGGAiCGCA)2 and an imino GA pairing forms in (GGiCGAiGCCA)2. The structures contrast with the formation of tandem imino and sheared GA pairs flanked by GC pairs in the RNA self-complementary duplexes (GCGGACGC)2 and (GGCGAGCC)2, respectively. In both iGiC duplexes, Watson-Crick like hydrogen bonds are formed between iG and iC, and iGiC substitutions result in less favorable loop stability. The results provide benchmarks for testing computations of molecular interactions that shape RNA three-dimensional structure.
microRNAs (miRNAs/miRs) may have a crucial function in tumor metastasis through the regulation of a plethora of signaling pathways. Increasing evidence has shown that miR-199a is important in regulating the tumor metastasis of ovarian cancer, although the precise biological function of miR-199a is unclear at present. In the current study, it was observed that the expression levels of miR-199a were higher in OV2008 cells compared with C13* cells. However, lower levels of mammalian target of rapamycin (mTOR) protein were detected by western blotting in the OV2008 cells compared with the C13* cells. The miR-199a levels were increased in the C13* cells using miR-199a mimics and the mTOR levels were observed to decrease. This may have resulted in a reversal of cisplatin resistance in the C13* cells. To test this hypothesis, the Renilla luciferase reporter gene system was used to analyze the mTOR levels. The results indicated that the expression levels of mTOR were significantly blocked by the increased miR-199a levels. When the miR-199a inhibitor was applied to decrease the miR-199a levels, it was observed that the mTOR expression levels were increased, while cisplatin-induced apoptosis was decreased in the OV2008 cells. The study concludes that miR-199a is able to reverse cisplatin resistance in human ovarian cancer cells through the inhibition of mTOR and that mTOR may be the target of miR-199a during this process.
microRNA-199a; mammalian target of rapamycin; cisplatin resistance; ovarian cancer cells
Antisense oligonucleotides (ASODNs) have been widely used as an important tool for regulating gene expression, and developed into therapeutics. Natural ODNs are susceptible to nuclease degradation, nucleic acid analogues, however, have less side effects, stronger stability and more potent activities. Large-scale de novo synthesis of a certain oligonucleotide has been very difficult and costly. In a previous preliminary study, we developed the polymerase-endonuclease amplification reaction (PEAR) for amplification and large-scale preparation of natural antisense ODNs. Here we extended the method in preparation of a widely used modified oligonucleotide with 5′-O-(1-Thiotriphosphate) modifications. Using electrospray ionization liquid chromatography mass spectrometry (ESI/LC/MS) detection, the purity of the PEAR product was measured as high as 100.0%. Using PEAR a large amount of a specific oligonucleotide can be produced starting from a small amount of synthetic seeds. It is suggested that PEAR can be a useful tool for large-scale production of modified oligonucleotides.
Chronic airway disorders, including chronic obstructive pulmonary disease (COPD), cystic fibrosis, and asthma, are associated with persistent pulmonary inflammation and goblet cell metaplasia and contribute to significant morbidity and mortality worldwide. While the molecular pathogenesis of these disorders is actively studied, little is known regarding the transcriptional control of goblet cell differentiation and mucus hyperproduction. Herein, we demonstrated that pulmonary allergen sensitization induces expression of FOXM1 transcription factor in airway epithelial and inflammatory cells. Conditional deletion of the Foxm1 gene from either airway epithelium or myeloid inflammatory cells decreased goblet cell metaplasia, reduced lung inflammation, and decreased airway resistance in response to house dust mite allergen (HDM). FOXM1 induced goblet cell metaplasia and Muc5AC expression through the transcriptional activation of Spdef. FOXM1 deletion reduced expression of CCL11, CCL24, and the chemokine receptors CCR2 and CX3CR1, resulting in decreased recruitment of eosinophils and macrophages to the lung. Deletion of FOXM1 from dendritic cells impaired the uptake of HDM antigens and decreased cell surface expression of major histocompatibility complex II (MHC II) and costimulatory molecule CD86, decreasing production of Th2 cytokines by activated T cells. Finally, pharmacological inhibition of FOXM1 by ARF peptide prevented HDM-mediated pulmonary responses. FOXM1 regulates genes critical for allergen-induced lung inflammation and goblet cell metaplasia.
Studies have demonstrated that autophagy pathways are activated in the brain after experimental subarachnoid hemorrhage (SAH) and this may play a protective role in early brain injury. However, the contribution of autophagy in the pathogenesis of cerebral vasospasm (CVS) following SAH, and whether up-regulated autophagy may contribute to aggravate or release CVS, remain unknown. Cystatin C (CysC) is a cysteine protease inhibitor that induces autophagy under conditions of neuronal challenge. This study investigated the expression of autophagy proteins in the walls of basilar arteries (BA), and the effects of CysC on CVS and autophagy pathways following experimental SAH in rats.
All SAH animals were subjected to injection of 0.3 mL fresh arterial, non-heparinized blood into the cisterna magna. Fifty rats were assigned randomly to five groups: control group (n = 10), SAH group (n = 10), SAH + vehicle group (n = 10), SAH + low dose of CysC group (n = 10), and SAH + high dose of CysC group (n = 10). We measured proteins by western blot analysis, CVS by H&E staining method, morphological changes by electron microscopy, and recorded neuro-behavior scores.
Microtubule-associated protein light chain-3, an autophagosome biomarker, and beclin-1, a Bcl-2-interacting protein required for autophagy, were significantly increased in the BA wall 48 h after SAH. In the CysC-handled group, the degree of CVS, measured as the inner BA perimeter and BA wall thickness, was significantly ameliorated in comparison with vehicle-treated SAH rats. This effect paralleled the intensity of autophagy in the BA wall induced by CysC.
These results suggest that the autophagy pathway is activated in the BA wall after SAH and CysC-induced autophagy may play a beneficial role in preventing SAH-induced CVS.
Autophagy; Cerebral Vasospasm; Cystatin C; Subarachnoid Hemorrhage
Hydrochloric acid is used in oil-well acidizing commonly for improving the crude oil production of the low-permeable reservoirs, while it is a great challenge for the metal instruments involved in the acidification. Developing natural products as oilfield chemicals is a straight way to find less expensive, green and eco-friendly materials. The great plant resources in Qin-ling and Ba-shan Mountain Area of Shannxi Province enable the investigating of new green oil field chemicals. Diospyros Kaki L.f (persimmon), a famous fruit tree is widely planted in Qin-ling and Ba-shan Mountain Area of Shaanxi Province. It has been found that the crude persimmon extracts are complex mixtures containing vitamins, p-coumaric acid, gallic acid, catechin, flavonoids, carotenoids and condensed tannin and so on, which indicates the extracts of persimmon husk suitable to be used as green and eco-friendly corrosion inhibitors.
Extracts of persimmon husk were investigated, by using weight loss and potentiodynamic polarisation techniques, as green and eco-friendly corrosion inhibitors of Q235A steel in 1M HCl. The inhibition efficiency of the extracts varied with extract concentration from 10 to 1,000 mg/L. There are some synergistic effects between the extracts and KI, KSCN and HMTA. Potentiodynamic polarization studies indicate that extracts are mixed-type inhibitors. Besides, the extracts were screened for antibacterial activity against oil field microorganisms, and they showed good to moderate activity against SRB, IB and TGB.
The inhibition efficiency of the extracts varied with extract concentration from 10 to 1,000 mg/L, and the highest reaches to 65.1% with the con concentration of 1,000 mg/L WE. KI, KSCN and HMTA they can enhance the IE of WE effectively to 97.3% at most, but not effective for KI and KSCN to AE. Tafel polarisation measurements indicate the extracts behave as mixed type inhibitor. Investigation of the antibacterial activity against oil field microorganism showed the extracts can inhibit SRB, IB and TGB with moderate to highly efficiency under 1,000 mg/L, which makes extracts potential to be used as bifunctional oil field chemicals.
Persimmon; Acid corrosion; Weight loss; Microbiological corrosion
Of great interest in recent years has been computationally predicting the novel polypharmacology of drug molecules. Here, we applied an “induced-fit” protocol to improve the homology models of 5-HT2A receptor, and we assessed the quality of these models in retrospective virtual screening. Subsequently, we computationally screened the FDA approved drug molecules against the best induced-fit 5-HT2A models, and chose six top scoring hits for experimental assays. Surprisingly, one well-known kinase inhibitor, sorafenib has shown unexpected promiscuous 5-HTRs binding affinities, Ki = 1959, 56 and 417 nM against 5-HT2A, 5-HT2B and 5-HT2C, respectively. Our preliminary SAR exploration supports the predicted binding mode, and further suggests sorafenib to be a novel lead compound for 5HTR ligand discovery. Although it has been well known that sorafenib produces anticancer effects through targeting multiple kinases, carefully designed experimental studies are desirable to fully understand whether its “off-target” 5-HTR binding activities contribute to its therapeutic efficacy or otherwise undesirable side effects.
GPCR; 5-HTR; induced-fit; molecular docking; molecular dynamics; sorafenib
AIM: To investigate the safety and efficacy of anus-preserving rectectomy via telescopic colorectal mucosal anastomosis (TCMA) for low rectal cancer.
METHODS: From August 1993 to October 2012, 420 patients including 253 males and 167 females with low rectal cancer underwent transabdominal and transanal anterior resection, followed by TCMA. The distance between the anus and inferior margin of the tumor ranged from 5 to 7 cm, and was 5 cm in 6 patients, 6 cm in 127, and 7 cm in 287 patients. Tumor-node-metastasis staging showed that 136 patients had stage I, 252 had stage II and 32 had stage III. Fifty-six patients with T3 or over received preoperative neoadjuvant chemoradiotherapy.
RESULTS: The postoperative follow-up rate was 91.9% (386/420) with a median time of 6.4 years. All 420 patients underwent radical resection. No postoperative death occurred. Postoperative complications included anastomotic leakage in 13 (3.1%) patients and anastomotic stenosis in 7 (1.6%). The local recurrence rate after surgery was 6.2%, the hepatic metastasis rate was 13.2% and the pulmonary metastasis rate was 2.3%. The 5-year survival rate was 74.0% and the disease-free survival rate was 71.0%. Kirwan classification showed that continence was good in 94.4% of patients with stage I when scored 12 mo after resection.
CONCLUSION: TCMA for patients with low rectal cancer leads to better quality of life and satisfactory defecation function, and lowers anastomotic leakage occurrence, and might be one of the safe operative procedures in anus-preserving rectectomy.
Low rectal cancer; Rectectomy; Telescopic colorectal mucosal anastomosis; Reconstruction; Abdominoperineal resection
Epithelial ovarian cancer (EOC) is the leading cause of female reproductive system cancer mortality in females. The majority of cases of ovarian carcinomas are not identified until a late stage. Identifying the molecular changes that occur during the development and progression of ovarian cancer is an urgent requirement. MicroRNAs (miRNAs) have been identified as gene expression regulators that induce mRNA degradation or translation blockade through pairing to the 3′ untranslated region (3-‘UTR) of the target mRNAs. In the present study, miR-222 was observed to be frequently upregulated in ovarian cancer. miR-222 upregulation induced an enhancement of ovarian cancer cell proliferation potential, possibly by downregulating its target, P27Kip1. A bioinformatic analysis showed that the 3′-UTR of the P27Kip1 mRNA contained a highly-conserved putative miR-222 binding site. Luciferase reporter assays demonstrated that P27Kip1 was a direct target of miR-222. Consistently, there was an inverse correlation between the P27Kip1 and miR-222 expression levels in the ovarian cancer cell lines and tissues. Overall, the present results suggest that miR-222 upregulation in human ovarian cancer may promote ovarian cancer cell proliferation during ovarian carcinogenesis.
epithelial ovarian cancer; miR-222; P27Kip1; carcinogenesis
The present study aimed to assess the prevalence of hypertension among Chinese adults.
Data were obtained from sphygmomanometer measurements and a questionnaire administered to 46239 Chinese adults ≥20 years of age who participated in the 2007–2008 China National Diabetes and Metabolic Disorders Study. Hypertension was defined as blood pressure ≥140/90 mm Hg or use of antihypertensive medication.
A total of 26.6% of Chinese adults had hypertension, and a significantly greater number of men were hypertensive than women (29.2% vs 24.1%, p<0.001). The age-specific prevalence of hypertension was 13.0%, 36.7%, and 56.5% among persons aged 20 to 44 years (young people), 45 to 64 years (middle-aged people), and ≥65 years (elderly people), respectively. In economically developed regions, the prevalence of hypertension was significantly higher among rural residents than among urban residents (31.3% vs 29.2%, p = 0.001). Among women or individuals who lived in the northern region, the disparity in the prevalence of hypertension between urban and rural areas disappeared (women: 24.0% vs. 24.0%, p = 0.942; northern region: 31.6% vs. 31.2%, p = 0.505). Among hypertensive patients, 45.0% were aware of their condition, 36.2% were treated, and 11.1% were adequately controlled.
The prevalence of hypertension in China is increasing. The trend of an increase in prevalence is striking in young people and rural populations. Hypertension awareness, treatment, and control are poor. Public health efforts for further improving awareness and enhancing effective control are urgently needed in China, especially in emerging populations.
Several lines of evidence support an important role for Snail, a transcriptional factor, in breast cancer. Overexpression of Snail has been associated with breast cancer metastasis, although the specific role of Snail in the process remains unclear. To address this issue, the expression levels of Snail, RhoA and fibronectin, as well as MMP-2, were reduced in the breast tumor cell lines MDA-MB-231 and MDA-MB-435S, and their biological responses were studied in vitro and in vivo. For the first time, it was observed that downregulated Snail expression is correlated with a significant inhibition of the expression and activity of RhoA GTPase, as well as MMP-2. The present data provide evidence that Snail promotes tumor cell motility and angiogenesis which is mainly mediated through the regulation of RhoA activity. In conclusion, the present findings demonstrate a key regulatory role for Snail in breast tumor growth and progression.
Snail; RhoA GTPase; metastasis; breast cancer
Histopathology forms the gold standard for the diagnosis of breast cancer. Multiphoton microscopy (MPM) has been proposed to be a potentially powerful adjunct to current histopathological techniques. A label-free imaging based on two- photon excited fluorescence and second-harmonic generation is developed for differentiating normal breast tissues, benign, as well as breast cancer tissues. Human breast biopsies (including human normal breast tissues, benign as well as breast cancer tissues ) that are first imaged (fresh, unfixed, and unstained) with MPM and are then processed for routine H-E histopathology. Our results suggest that the MPM images, obtained from these unprocessed biopsies, can readily distinguish between benign lesions and breast cancers. In the tissues of breast cancers, MPM showed that the tumor cells displayed marked cellular and nuclear pleomorphism. The tumor cells, characterized by irregular size and shape, enlarged nuclei, and increased nuclear-cytoplasmic ratio, infiltrated into disrupted connective tissue, leading to the loss of second-harmonic generation signals. For breast cancer, MPM diagnosis was 100% correct because the tissues of breast cancers did not have second-harmonic generation signals in MPM imaging. On the contrary, in benign breast masses, second-harmonic generation signals could be seen easily in MPM imaging. These observations indicate that MPM could be an important potential tool to provide label-free noninvasive diagnostic impressions that can guide surgeon in biopsy and patient management.
Depressive symptoms often coexist with memory deficits in older adults and also are associated with incident cognitive decline in the elderly. However, little is known about the neural correlates of the association between depressive symptoms and memory deficits in nondemented elderly. Fifteen amnestic mild cognitive impairment (aMCI) and 20 cognitively normal (CN) subjects completed resting-state functional magnetic resonance imaging (R-fMRI) scans. Multiple linear regression analysis was performed to test the main effects of the Geriatric Depression Scale (GDS) and Rey Auditory Verbal Learning Test delayed recall (RAVLT-DR) scores, and their interaction on the intrinsic amygdala functional connectivity (AFC) network activity. Severer depressive symptoms and memory deficits were found in the aMCI group than in the CN group. Partial correlation analysis identified that the RAVLT-DR scores were significantly correlated with the AFC network in the bilateral dorsolateral prefrontal cortex (DLPFC), dorsomedial and anterior prefrontal cortex, posterior cingulate cortex (PCC), middle occipital gyrus, right inferior parietal cortex, and left middle temporal gyrus (MTG). The GDS scores were positively correlated with the AFC network in the bilateral PCC and MTG, and left DLPFC. The interactive effects of the GDS and RAVLT-DR scores on the AFC network were seen in the bilateral PCC, MTG, and left DLPFC. These findings not only supported that there were interactive neural links between depressive symptoms and memory functions in nondemented elderly at the system level, but also demonstrated that R-fMRI has advantages in investigating the interactive nature of different neural networks involved in complex functions, such as emotion and cognition.
amnestic mild cognitive impairment; depressive symptom; memory deficits; resting-state functional connectivity MRI; amygdala
Alcohol consumption is a risk factor for breast cancer in humans. Experimental studies indicate that alcohol exposure promotes malignant progression of mammary tumors. However, the underlying cellular and molecular mechanisms remain unclear. Alcohol induces a pro-inflammatory response by modulating the expression of cytokines and chemokines. Monocyte chemoattractant protein-1 (MCP-1), also known as chemokine (C-C motif) ligand 2 (CCL2), is a pro-inflammatory chemokine implicated in breast cancer development/malignancy. We investigated the role of MCP-1 in alcohol-promoted mammary tumor progression. Using a xenograft model, we demonstrated that alcohol increased tumor angiogenesis and promoted growth/metastasis of breast cancer cells in C57BL/6 mice. Alcohol up-regulated the expression of MCP-1 and its receptor CCR2 in breast cancer cells in vitro and in vivo. Using a three-dimensional (3-D) tumor/endothelial cell co-culture system, we demonstrated MCP-1 regulated tumor/endothelial cell interaction and promoted tumor angiogenesis. More importantly, MCP-1 mediated alcohol-promoted angiogenesis; an antagonist of the MCP-1 receptor CCR2 significantly inhibited alcohol-stimulated tumor angiogenesis. The CCR2 antagonist abolished ethanol-stimulated growth of mammary tumors in mice. We further demonstrated that MCP-1 enhanced the migration, but not the proliferation of endothelial cells as well as breast cancer cells. These results suggest that MCP-1 plays an important role in ethanol-stimulated tumor angiogenesis and tumor progression.
Alcohol; angiogenesis; chemokines; metastasis; migration
This study investigated the impact of family history of diabetes (FHD) on β-cell function among Chinese with normal glucose tolerance.
Research Design and Methods
A multistage, stratified, cluster random sampling method was used to select a provincially representative sample from Fujian Province. Eventually, a total of 1,183 subjects were entered into the analysis. Several indexes were used to assess the function of β cells, including homeostasis model assessment (HOMA) of insulin resistance (IR), HOMA of β cells, insulinogenic index (IGI), and disposition index.
Overweight, increased body mass index, higher low-density lipoprotein cholesterol, and higher total cholesterol (TC) were the dominant features of positive FHD (FHD+). The FHD+ subjects had lower insulin sensitivity (P<0.05). FHD+ subjects showed higher risk of IR after adjusting for other risk factors (odds ratio 1.523 [1.272–2.009]). However, there was no significant difference in insulin secretion between the two groups. With the use of the multiple linear regression model, waist circumference (WC) and triglycerides (TGs) were found to be independent risk factors of the decline of insulin sensitivity in FHD+ subjects, and insulin sensitivity declined significantly (P<0.05) with the increase of WC and TGs. In addition, the offspring of fathers with diabetes (PT2D) were much older and had higher TC than those of mothers with diabetes (MT2D). After adjusting for gender of the parents, there was no difference between MT2D and PT2D on insulin sensitivity.
Inheritance if diabetes is associated with the decline of insulin sensitivity. In addition, insulin sensitivity declined with increasing WC and TG in FHD+ subjects.