The catalytic properties of nanostructured Au and their physical origin were investigated by using the low-temperature CO oxidation as a test reaction. In order to distinguish between structural effects (structure–activity correlations) and bimetallic/bifunctional effects, unsupported nanoporous gold (NPG) samples prepared from different Au alloys (AuAg, AuCu) by selective leaching of a less noble metal (Ag, Cu) were employed, whose structure (surface area, ligament size) as well as their residual amount of the second metal were systematically varied by applying different potentials for dealloying. The structural and chemical properties before and after 1000 min reaction were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The catalytic behavior was evaluated by kinetic measurements in a conventional microreactor and by dynamic measurements in a temporal analysis of products (TAP) reactor. The data reveal a clear influence of the surface contents of residual Ag and Cu species on both O2 activation and catalytic activity, while correlations between activity and structural parameters such as surface area or ligament/crystallite size are less evident. Consequences for the mechanistic understanding and the role of the nanostructure in these NPG catalysts are discussed.
AuAg alloy; AuCu alloy; CO oxidation; dynamic studies; kinetics; nanoporous Au (NPG) catalyst; oxygen storage capacity (OSC); temporal analysis of products (TAP)
To investigate the effect of Y-27632 on the survival and neurite outgrowth of the cultured retinal neurocytes.
After the postnatal day 2-3, Sprague-Dawley retinal neurocytes were cultured for 48 hours, the culture media was replaced with serum-free media (control group) and serum-free media contained 30µmol/L Y-27632 (Y-27632 group), and the cells were continually cultured another 48 hours. The cultured retinal neurocytes were identified with anti-neuron specific enolase (NSE) immunocytochemistry. The survival state of those cells was estimated by MTT assay, and the neurite outgrowth of those cells was evaluated by the computerized image-analysis system.
Compared with the control group, the absorbance values of cells survival in Y-27632 group increased 12.90% and 33.33% respectively after 72 and 96 hours culture. Y-27632 had no significant effect on the diameter of cultured retinal neurocytes. Compared with the control group, Y-27632 induced a stable improvement of neurite outgrowth of retinal neurocytes after 72 and 96 hours culture (P=0.001).
Y-27632 could promote the survival and neurite outgrowth of the early postnatal cultured retinal neurocytes.
Y-27632; retinal neurocytes; cell culture; neurites
Poorly differentiated neuroendocrine carcinomas (NEC) of the pancreas are rare malignant neoplasms with a poor prognosis. The aim of this study was to determine the clinicopathologic and genetic features of poorly differentiated NECs and compare them to other types of pancreatic neoplasms. We investigated alterations of KRAS, CDKN2A/p16, TP53, SMAD4/DPC4, DAXX, ATRX, PTEN, Bcl2 and RB1 by immunohistochemistry and/or targeted exomic sequencing in surgically resected specimens of nine small cell NEC, 10 large cell NECs and 11 well-differentiated neuroendocrine tumors (PanNETs) of the pancreas. Abnormal immunolabeling patterns of p53 and Rb were frequent (p53, 18 of 19, 95%; Rb, 14 of 19, 74%) in both small cell and large cell NEC, whereas Smad4/Dpc4, DAXX and ATRX labeling were intact in virtually all of these same carcinomas. Abnormal immunolabeling of p53 and Rb proteins correlated with intragenic mutations in the TP53 and RB1 genes. By contrast, DAXX and ATRX was lost in 45% of PanNETs whereas p53 and Rb immunolabeling was intact in these same cases. Overexpression of Bcl-2 protein was observed in all nine small cell NECs (100%) and in five of 10 (50%) large cell NECs compared to only two of 11 (18%) PanNETs. Bcl-2 overexpression was significantly correlated with higher mitotic rate and Ki-67 labeling index in neoplasms in which it was present. Small cell NECs are genetically similar to large cell NECs, and these genetic changes are distinct from those reported in PanNETs. The finding of Bcl-2 overexpression in poorly differentiated NECs, particularly small cell NEC, suggests that Bcl-2 antagonists/inhibitors may be a viable treatment option for these patients.
A street rabies virus (RV) isolate, GXHXN, was obtained from brain tissue of rabid cattle in the Guangxi Zhuang Autonomous Region of China in 2009. GXHXN is the first isolate from cattle in China with its entire genome sequenced and is closely related to BJ2011E from horse in Beijing, WH11 from donkey in the Hubei Province, and isolates from dogs in the Guangxi and Fujian Provinces, with homologies of 97.6% to 99.6%. It is more distantly related to isolates from domestic cat, pig, Chinese ferret badger, and vaccine strains, with homologies of 83.1% to 88.0%.
Traditional serrated adenomas (TSAs) are a type of colorectal polyp with neoplastic potential. Immunohistochemical analysis and sequencing were performed on 24 TSAs from 23 patients to characterize the molecular genetics of TSAs. Abnormal Ki-67 and p53 labeling were observed in 7 (29%) of 24 and 6 (25%) of 24 TSAs, respectively; both types were significantly associated with the presence of conventional epithelial dysplasia (P = .0005 and P = .0001, respectively). Activating KRAS mutation was identified in 11 TSAs (46%) and was mutually exclusive with activating BRAF mutations, which were seen in 7 TSAs (29%). Abnormal p53 nuclear labeling in a TSA was significantly associated with BRAF mutation status (P = .04), whereas no relationship was found for β-catenin labeling patterns. The overall morphologic features of TSA do not correlate with the genetic status of the KRAS and BRAF genes. However, conventional epithelial dysplasia and abnormal p53 labeling in a TSA are seen more often in the setting of BRAF mutation.
Traditional serrated adenoma; KRAS; Colon polyp; BRAF; p53
Leprosy is a disabling chronic infection, with insidious onset that often evades early detection. In order to detect new leprosy cases in a timely manner, we conducted surveillance visits in some difficult-to-reach mountain areas in South West China where the disease is still prevalent. Our data confirm that Chinese multibacillary (MB) leprosy patients have strong antibody responses against Mycobacterium leprae antigens ND-O-BSA and LID-1. Contacts of clinically diagnosed patients were then monitored at regular intervals by both physical examinations and the laboratory determination of antibody responses in sera collected during these examinations. Elevations in antibody titers indicated the onset of MB leprosy in one of the contacts, and diagnosis was subsequently confirmed on physical examination. Our data indicate that rising antibody titers can be used as a trigger for physical examination or increased monitoring of particular individuals in order to provide early leprosy diagnosis.
The current identification of microRNAs (miRNAs) in insects is largely dependent on genome sequences. However, the lack of available genome sequences inhibits the identification of miRNAs in various insect species. In this study, we used a miRNA database of the silkworm Bombyx mori as a reference to identify miRNAs in Helicoverpa armigera and Spodoptera litura using deep sequencing and homology analysis. Because all three species belong to the Lepidoptera, the experiment produced reliable results. Our study identified 97 and 91 conserved miRNAs in H. armigera and S. litura, respectively. Using the genome of B. mori and BAC sequences of H. armigera as references, 1 novel miRNA and 8 novel miRNA candidates were identified in H. armigera, and 4 novel miRNA candidates were identified in S. litura. An evolutionary analysis revealed that most of the identified miRNAs were insect-specific, and more than 20 miRNAs were Lepidoptera-specific. The investigation of the expression patterns of miR-2a, miR-34, miR-2796-3p and miR-11 revealed their potential roles in insect development. miRNA target prediction revealed that conserved miRNA target sites exist in various genes in the 3 species. Conserved miRNA target sites for the Hsp90 gene among the 3 species were validated in the mammalian 293T cell line using a dual-luciferase reporter assay. Our study provides a new approach with which to identify miRNAs in insects lacking genome information and contributes to the functional analysis of insect miRNAs.
microRNA; deep sequencing; homolog analysis; Helicoverpa armigera; Spodoptera litura; Bombyx mori.
We occasionally found that cestode Taenia taeniaeformis in rats favored Sporothrix schenckii infection and survival, causing protracted cutaneous lesions. In this study, we compared the pathology and cytokines profile of rats co-infected with the two pathogens and infected with S. schenckii alone to explore underlying mechanisms. In the co-infection group, there was high expression of β-glucan receptor Dectin-1 in the cutaneous lesions and no multinucleated giant cells, but in the S. schenckii infection group the opposite was observed. Cytokines profiles demonstrated an expected finding that IL-4, commonly expressed in helminth and fungus infection, is undetectable in the two infection groups. In the single fungal infection group, cytokines IFN-γ, IL-10 and IL-17 kept increasing in the first few weeks of infection to a peak which was followed by gradual decrease. This study showed that Dectin-1 and IL-17, which were believed to be the major anti-fungus mechanisms, are Th2 independent and dispensable for clearance of S. schenckii infection, suggesting that S. schenckii has a different molecular recognition pattern and evokes anti-infection mechanisms other than Dectin-1 and IL-17.
Extensive molecular, genetic, and anatomical analyses have suggested that olfactory memory is stored in the mushroom body (MB), a higher-order olfactory center in the insect brain. The MB comprises of three subtypes of neurons whose axons extend into different lobes. A recent functional imaging study has revealed a long-term memory trace manifested as an increase in the Ca2+ activity in an axonal branch of a subtype of MB neurons. However, early memory traces in the MB remain elusive. We report here learning-induced changes in Ca2+ activities during early memory formation in a different subtype of MB neurons. We used three independent in vivo and in vitro preparations, and all of them showed that Ca2+ activities in the axonal branches of α′/β′ neurons in response to a conditioned olfactory stimulus became larger compared to one that was not conditioned. The changes were dependent on proper G protein signaling in the MB. The importance of these changes in the Ca2+ activity of α′/β′ neurons during early memory formation was further tested behaviorally by disrupting G protein signaling in these neurons or blocking their synaptic outputs during the learning and memory process. Our results suggest that increased Ca2+ activity in response to conditioned olfactory stimulus may be a neural correlate of early memory in the MB.
learning and memory; Drosophila; imaging; calcium; Olfactory; Fluorescence microscopy
To determine the variation of IFN-γ and IL-17 responses to M. tuberculosis antigens in healthy TST+ humans.
We isolated peripheral blood mononuclear cells from 21 TST+ healthy adults, stimulated them with phytohemagglutinin (PHA), PPD, Ag85B, ESAT-6, and live M. bovis BCG, and assayed IFN-γ and IL-17 secretion by ELISA in supernatants after 24 or 72 hours of incubation respectively.
As in other studies, we found a wide range of IFN-γ responses to M. tuberculosis antigens; the variation significantly exceeded that observed in the same donors to the polyclonal T cell stimulus, phytohemagglutinin (PHA). In addition, we assayed IL-17 secretion in response to the same stimuli, and found less subject-to-subject variation. Analysis of the ratio of IFN-γ to IL-17 secretion on a subject-to-subject basis also revealed a wide range, with the majority of results distributed in a narrow range, and a minority with extreme results all of which were greater than that in the majority of subjects. The data suggest that study of exceptional responses to M. tuberculosis antigens may reveal immunologic correlates with specific outcomes of M. tuberculosis infection.
Variation of IFNγ and IFN-γ/IL-17 responses to mycobacterial antigens exceeds that of responses to the polyclonal stimulus, PHA, in TST positive healthy humans. This indicates a quantitative spectrum of human immune responses to infection with M. tuberculosis. Since the outcome of human infection with M. tuberculosis varies greatly, systematic study of multiple immune responses to multiple antigens is likely to reveal correlations between selected immune responses and the outcomes of infection.
Small cell carcinoma (SCC) of the pancreas is a rare malignancy with a poor prognosis. We established and characterized a primary human pancreatic SCC cell line, designated A99.
Cancer tissue was obtained from the liver metastasis of a SCC of the pancreas and xenografted into nude mice. The first-pass xenograft was then used to establish a cultured cell line called A99. Cellular morphology, immunohistochemical properties, tumorigenic potential, and genetic alterations of this new line were characterized.
A99 cells grew consistently in culture, formed colonies in soft agar and grew as subcutaneous xenografts when inoculated into nude mice. A99 cells were positive for pancytokeratin, synaptophysin, chromogranin A, NSE, CD57 (Leu7), CD56, PGP 9.5, TTF-1, Smad4, p53 and p16 but not for CD99, PDX-1 or RB protein. Sequencing analysis revealed homozygous point mutations of KRAS and TP53. Cytogenetic analysis revealed complex chromosomal rearrangements including marker chromosomes.
A99 is the first cell line report to be derived from a primary SCC of the pancreas. The establishment of this cell line may serve as a useful model system for studying the cell biology of this rare cancer, or for evaluation of novel targeted agents in preclinical models.
cell line; small cell carcinoma; pancreas; neuroendocrine neoplasm; molecular genetics
The virulence-attenuated Leptospira interrogans serovar Lai strain IPAV was derived by prolonged laboratory passage from a highly virulent ancestral strain isolated in China. We studied the genetic variations of IPAV that render it avirulent via comparative analysis against the pathogenic L. interrogans serovar Lai strain 56601. The complete genome sequence of the IPAV strain was determined and used to compare with, and then rectify and reannotate the genome sequence of strain 56601. Aside from their highly similar genomic structure and gene order, a total of 33 insertions, 53 deletions and 301 single-nucleotide variations (SNVs) were detected throughout the genome of IPAV directly affecting 101 genes, either in their 5′ upstream region or within their coding region. Among them, the majority of the 44 functional genes are involved in signal transduction, stress response, transmembrane transport and nitrogen metabolism. Comparative proteomic analysis based on quantitative liquid chromatography (LC)-MS/MS data revealed that among 1 627 selected pairs of orthologs, 174 genes in the IPAV strain were upregulated, with enrichment mainly in classes of energy production and lipid metabolism. In contrast, 228 genes in strain 56601 were upregulated, with the majority enriched in the categories of protein translation and DNA replication/repair. The combination of genomic and proteomic approaches illustrated that altered expression or mutations in critical genes, such as those encoding a Ser/Thr kinase, carbon-starvation protein CstA, glutamine synthetase, GTP-binding protein BipA, ribonucleotide-diphosphate reductase and phosphate transporter, and alterations in the translational profile of lipoproteins or outer membrane proteins are likely to account for the virulence attenuation in strain IPAV.
genome; proteome; Leptospira; virulence; mutation
Inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is being pursued as a new therapeutic approach for the treatment of obesity and metabolic syndrome. Therefore, there is an urgent need to determine the effect of 11β-HSD1 inhibitor, which suppresses glucocorticoid action, on adipose tissue inflammation. The purpose of the present study was to examine the effect of BVT.2733, a selective 11β-HSD1 inhibitor, on expression of pro-inflammatory mediators and macrophage infiltration in adipose tissue in C57BL/6J mice.
C57BL/6J mice were fed with a normal chow diet (NC) or high fat diet (HFD). HFD treated mice were then administrated with BVT.2733 (HFD+BVT) or vehicle (HFD) for four weeks. Mice receiving BVT.2733 treatment exhibited decreased body weight and enhanced glucose tolerance and insulin sensitivity compared to control mice. BVT.2733 also down-regulated the expression of inflammation-related genes including monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-α) and the number of infiltrated macrophages within the adipose tissue in vivo. Pharmacological inhibition of 11β-HSD1 and RNA interference against 11β-HSD1 reduced the mRNA levels of MCP-1 and interleukin-6 (IL-6) in cultured J774A.1 macrophages and 3T3-L1 preadipocyte in vitro.
These results suggest that BVT.2733 treatment could not only decrease body weight and improve metabolic homeostasis, but also suppress the inflammation of adipose tissue in diet-induced obese mice. 11β-HSD1 may be a very promising therapeutic target for obesity and associated disease.
The aggregation or oligomerization of amyloid-β (Aβ) peptide is thought to be the primary causative event in the pathogenesis of Alzheimer's disease (AD). Considerable in vitro evidence indicates that the aggregation/oligomerization of Aβ is promoted in the presence of Zn; however, the functional role of Zn in AD pathogenesis is still not well clarified in vivo. Zn is imported into the brain mainly through the solute-linked carrier (Slc) 39 family transporters. Using a genetically tractable Drosophila model, we found that the expression of dZip1, the orthologue of human Slc39 family transporter hZip1 in Drosophila, was altered in the brains of Aβ42-expressing flies, and Zn homeostasis could be modulated by forcible dZip1 expression changes. An array of phenotypes associated with Aβ expression could be modified by altering dZip1 expression. Importantly, Aβ42 fibril deposits as well as its SDS-soluble form were dramatically reduced upon dZip1 inhibition, resulting in less neurodegeneration, significantly improved cognitive performance, and prolonged lifespan of the Aβ42-transgenic flies. These findings suggest that zinc contributes significantly to the Aβ pathology, and manipulation of zinc transporters in AD brains may provide a novel therapeutic strategy.
Alzheimer's disease (AD) is characterized by extracellular amyloid plaques and altered metal ion (including Zn, Cu, Fe) concentrations in the brain. Amyloid plaques are the result of increased aggregation of Aβ, while the in vivo role of metal ions such as Zn remains poorly understood. We found that the expression of a zinc transporter (dZip1) is altered in the brains of AD flies. Genetic manipulation of dZip1 to modulate its expression was accompanied by altered Aβ accumulation, resulting in changes in the neurodegeneration development, cognitive performance, and lifespan of the AD flies. These genetic findings support the zinc role in AD pathology and implicate a new therapeutic target for treating AD.
Patients with chronic pain usually suffer from working memory deficits, which may decrease their intellectual ability significantly. Despite intensive clinical studies, the mechanism underlying this form of memory impairment remains elusive. In this study, we investigated this issue in the spared nerve injury (SNI) model of neuropathic pain, a most common form of chronic pain. We found that SNI impaired working memory and short-term memory in rats and mice. To explore the potential mechanisms, we studied synaptic transmission/plasticity in hippocampus, a brain region critically involved in memory function. We found that frequency facilitation, a presynaptic form of short-term plasticity, and long-term potentiation at CA3–CA1 synapses were impaired after SNI. Structurally, density of presynaptic boutons in hippocampal CA1 synapses was reduced significantly. At the molecular level, we found that tumor necrosis factor-α (TNF-α) increased in cerebrospinal fluid, in hippocampal tissue and in plasma after SNI. Intracerebroventricular or intrahippocampal injection of recombinant rat TNF mimicked the effects of SNI in naive rats, whereas inhibition of TNF-α or genetic deletion of TNF receptor 1 prevented both memory deficits and synaptic dysfunction induced by SNI. As TNF-α is critical for development of neuropathic pain, we suggested that the over-production of TNF-α following peripheral nerve injury might lead to neuropathic pain and memory deficits, simultaneously.
spared nerve injury; chronic neuropathic pain; working memory; long-term potentiation; presynaptic boutons; tumor necrosis factor-α; pain/analgesics; learning & memory; neuropharmacology; plasticity; peripheral nerve injury; chronic neuropathic pain; working memory; long-term potentiation; presynaptic boutons; tumor necrosis factor alpha
Aim. To compare the basic endocrine profile and outcomes of in vitro fertilization (IVF) in women with polycystic ovary syndrome (PCOS), ovulatory polycystic ovaries (PCO), or normal ovaries (NO). Methods. The basic clinical features and in vitro fertilization and embryo transfer outcome in patients receiving IVF or intracytoplasmic sperm injection (ICSI) were retrospectively analyzed. Results. The body mass index, basal luteinizing hormone, and testosterone levels were significantly lower in patients with ovulatory PCO compared to those in patients with PCOS. The PCOS patients exhibited the shortest duration of ovarian stimulation and lowest dose of gonadotropin, followed by the ovulatory PCO and NO patients. The ovulatory PCO and PCOS patients showed similar levels of E2 on the human chorionic gonadotropin treatment day and numbers of oocytes, which were both significantly higher than those of the NO patients. The fertilization rate of the PCOS patients was significantly lower than the other two groups. Compared to NO patients, the cleavage rate was lower in both PCOS and ovulatory PCO patients, however, the number of available embryos was significantly more in these two groups. The incidence of the moderate to severe ovarian hyperstimulation syndrome (OHSS) was markedly higher in the PCOS and ovulatory PCO patients. Conclusion. Ovulatory PCO patients do not express similar endocrine abnormalities as PCOS patients. Although the fertilization rate and cleavage rate were relatively low in PCOS patients, ultimately, all the three groups showed similar transferred embryo numbers, clinical pregnancy rates, and implantation rates. Since the incidence of OHSS was much higher in the PCOS and ovulatory PCO patients, we should take more care of these patients and try to prevent severe OHSS.
Objective: To investigate the impact of antithyroid antibody on pregnancy outcome following the in vitro fertilization and embryo transfer (IVF-ET).
Methods: A total of 90 patients (156 cycles) positive for antithyroid antibody (ATA+ group) and 676 infertile women (1062 cycles) negative for antithyroid antibody (ATA- group) undergoing IVF/ICSI from August 2009 to August 2010 were retrospectively analyzed.
Results: There was no significant difference in the days of ovarian stimulation, total gonadotropin dose, serum E2 level of HCG day and number of oocytes retrieved between the two groups. The fertilization rate, implantation rate and pregnancy rate following IVF-ET were significantly lower in women with antithyroid antibody than in control group (64.3% vs 74.6%, 17.8% vs 27.1% and 33.3% vs 46.7%, respectively), but the abortion rate was significantly higher in patients with antithyroid antibody (26.9% vs 11.8%).
Conclusion: Patients with antithyroid antibody showed significantly lower fertilization rate, implantation rate and pregnancy rate and higher risk for abortion following IVF-ET when compared with those without antithyroid antibody. Thus, the presence of antithyroid antibody is detrimental for the pregnancy outcome following IVF-ET.
thyroid auto-antibodies; in vitro fertilization and embryo transfer; pregnancy outcome
Rho-associated kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase RhoA. The Rho/ROCK pathway is closely related to the pathogenesis of several central nervous system (CNS) disorders, and involved in many aspects of neuronal functions including neurite outgrowth and retraction. In the adult CNS, the damaged neuron regeneration is very difficult due to the presence of myelin-associated axon growth inhibitors such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (Omgp), etc. The effects of these axon growth inhibitors are reversed by blocking the Rho/ROCK pathway in vitro, and the inhibition of Rho/ROCK pathway can promote axon regeneration and functional recovery in the injured CNS in vivo. In addition, the therapeutic effects of the Rho/ROCK inhibitors have also been demonstrated in some animal models and the Rho/ROCK pathway becomes an attractive target for the development of drugs for treating CNS disorders. In this review, we summarized on the effect of the Rho and the downstream factor ROCK in neural regeneration, and the potential therapeutic effect of Rho/ROCK inhibitors in the survival and axonal regeneration of retinal ganglion cells was also discussed.
Rho/ROCK pathway; neural regeneration; potential therapeutic effect; optic nerve damage
To evaluate the frequency of blue-on-yellow perimetry (B/YP) deficits in ocular hypertension (OHT) patients and to correlate these findings with central corneal thickness (CCT), and to investigate the influence of age, refraction and gender on the B/YP results in OHT patients.
The B/YP and CCT were checked respectively in 72 OHT patients with normal white-on-white perimetry(W/WP) and normal optic nerve head. The B/YP was tested by Octopus 101 automated perimetry using G2 strategy, while the CCT was checked with DGH-550 ultrasound pachymeter. All patients were chosen randomly one eye for statistical analysis, a binary regression model was used to determine the independent contribution of variables included in the model, and the differences of the intraocular pressure (IOP), CCT, age, refraction and gender between the normal B/YP group and abnormal B/YP group were compared.
Forty-nine out of 72 patients with OHT showed normal B/YP results, whereas 23 of 72 patients(31.9%) demonstrated abnormal B/YP results. CCT showed a correlation with the B/YP results (B=-0.038, SE=0.019, P=0.044), whereas none of the IOP, age, refraction and gender was found to be correlated with the B/YP results. The mean CCT in OHT patients with abnormal B/YP group was lower than that with normal B/YP group (t=2.066, P=0.043).There was a significant positive correlation between IOP and CCT (R2=0.513, P=0.000).
The mean CCT in OHT patients with abnormal B/YP results was lower than that with normal B/YP results. There was a significant positive correlation between IOP and CCT in OHT patients. The age, refraction and gender didn't influence the B/YP results in OHT patients.
ocular hypertension; blue-on-yellow perimetry; central corneal thickness; visual function
Persuasive epidemiological and experimental evidence suggests that dietary flavonoids have anti-cancer activity. Since conventional therapeutic and surgical approaches have not been able to fully control the incidence and outcome of most cancer types, including colorectal neoplasia, there is an urgent need to develop alternative approaches for the management of cancer. We sought to develop the best flavonoids for the inhibition of cell growth, and apigenin (flavone) proved the most promising compound in colorectal cancer cell growth arrest. Subsequently, we found that pro-apoptotic proteins (NAG-1 and p53) and cell cycle inhibitor (p21) were induced in the presence of apigenin, and kinase pathways, including PKCδ and ataxia telangiectasia mutated (ATM), play an important role in activating these proteins. The data generated by in vitro experiments were confirmed in an animal study using APCMIN+ mice. Apigenin is able to reduce polyp numbers, accompanied by increasing p53 activation through phosphorylation in animal models. Our data suggest apparent beneficial effects of apigenin on colon cancer.
Apigenin; p53; p21; NAG-1; PKCδ; colorectal cancer
Background and Objectives: Chronic kidney disease (CKD) is a growing public health problem with an urgent need for new pharmacological agents. Cordyceps cicadae is widely used in traditional Chinese medicine (TCM) and has potential renoprotective benefits. The current study aimed to determine any scientific evidence to support its clinical use. Methods: We analyzed the potential of two kinds of C. cicadae extract, total extract (TE) and acetic ether extract (AE), in treating kidney disease simulated by a subtotal nephrectomy (SNx) model. Sprague-Dawley rats were divided randomly into seven groups: sham-operated group, vehicle-treated SNx, Cozaar, 2 g/(kg∙d) TE SNx, 1 g/(kg∙d) TE SNx, 92 mg/(kg∙d) AE SNx, and 46 mg/(kg∙d) AE SNx. Renal injury was monitored using urine and serum analyses, and hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) stainings were used to analyze the level of fibrosis. The expression of type IV collagen (Col IV), fibronectin (FN), transforming growth factor-β1 (TGF-β1), and connective tissue growth factor (CTGF) was detected by immunohistochemistry. Results: Renal injury, reflected in urine and serum analyses, and pathological changes induced by SNx were attenuated by TE and AE intervention. The depositions of Col IV and FN were also decreased by the treatments and were accompanied by reduced expression of TGF-β1 and CTGF. In some respects, 2 g/(kg∙d) of TE produced better effects than Cozaar. Conclusions: For the first time, we have shown that C. cicadae may inhibit renal fibrosis in vivo through the TGF-β1/CTGF pathway. Therefore, we conclude that the use of C. cicadae could provide a rational strategy for combating renal fibrosis.
Chronic kidney disease; Cordyceps cicadae; TGF-β; Traditional Chinese medicine
Astrocyte elevated gene-1 (AEG-1) is associated with tumorigenesis and progression in diverse human cancers. The present study was aimed to investigate the clinical and prognostic significance of AEG-1 in salivary gland carcinomas (SGC).
Real-time PCR and western blot analyses were employed to examine AEG-1 expression in two normal salivary gland tissues, eight SGC tissues of various clinical stages, and five pairs of primary SGC and adjacent salivary gland tissues from the same patient. Immunohistochemistry (IHC) was performed to examine AEG-1 protein expression in paraffin-embedded tissues from 141 SGC patients. Statistical analyses was applies to evaluate the diagnostic value and associations of AEG-1 expression with clinical parameters.
AEG-1 expression was evidently up-regulated in SGC tissues compared with that in the normal salivary gland tissues and in matched adjacent salivary gland tissues. AEG-1 protein level was positively correlated with clinical stage (P < 0.001), T classification (P = 0.008), N classification (P = 0.008) and M classifications (P = 0.006). Patients with higher AEG-1 expression had shorter overall survival time, whereas those with lower tumor AEG-1 expression had longer survival time.
Our results suggest that AEG-1 expression is associated with SGC progression and may represent a novel and valuable predictor for prognostic evaluation of SGC patients.
AEG-1; Biomarker; Prognosis; Salivary gland carcinomas
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease characterized by late diagnosis and treatment resistance. Recurrent genetic alterations in defined genes in association with perturbations of developmental cell signaling pathways have been associated with PDAC development and progression. Here, we show that GATA6 contributes to pancreatic carcinogenesis during the temporal progression of pancreatic intraepithelial neoplasia by virtue of Wnt pathway activation. GATA6 is recurrently amplified by both quantitative-PCR and fluorescent in-situ hybridization in human pancreatic intraepithelial neoplasia and in PDAC tissues, and GATA6 copy number is significantly correlated with overall patient survival. Forced overexpression of GATA6 in cancer cell lines enhanced cell proliferation and colony formation in soft agar in vitro and growth in vivo, as well as increased Wnt signaling. By contrast siRNA mediated knockdown of GATA6 led to corresponding decreases in these same parameters. The effects of GATA6 were found to be due to its ability to bind DNA, as forced overexpression of a DNA-binding mutant of GATA6 had no effects on cell growth in vitro or in vivo, nor did they affect Wnt signaling levels in these same cells. A microarray analysis revealed the Wnt antagonist Dickopf-1 (DKK1) as a dysregulated gene in association with GATA6 knockdown, and direct binding of GATA6 to the DKK1 promoter was confirmed by chromatin immunoprecipitation and electrophoretic mobility shift assays. Transient transfection of GATA6, but not mutant GATA6, into cancer cell lines led to decreased DKK1 mRNA expression and secretion of DKK1 protein into culture media. Forced overexpression of DKK1 antagonized the effects of GATA6 on Wnt signaling in pancreatic cancer cells. These findings illustrate that one mechanism by which GATA6 promotes pancreatic carcinogenesis is by virtue of its activation of canonical Wnt signaling via regulation of DKK1.
The aim of the present article was to review the current new knowledge on the molecular markers of tumor invasion in ameloblastoma. In this review, tumor molecular markers were identified and allocated to the following six groups according to their functions: (I) Markers involved in extracellular matrix degradation, (II) Molecular markers involved in cell adhesion lost, (III) Molecular markers involved in bone remodeling, (IV) Cytokines involved in angiogenesis, (V) Molecular markers related with the function of tumor stromal cells on the invasion of ameloblastoma, and (VI) Molecular markers involved in cell proliferation related with invasion.
In general, the location of markers within the tumor and not their quantitative assessments as such is emphasized. Data showed that the correlation among molecular markers of invasive relevance is still not quite clear. Results on markers of tumor invasion and metastatic potential appeared to be too premature for a statement regarding the instinct invasive nature of ameloblastoma. The unraveling of specific new details concerning these mechanisms, whereby the expression and relationships among the molecules are mediated, may provide an opportunity to afford efficient prevention and develop new treatment therapies.
Ameloblastoma; molecules; tumor invasion
Genetic screens for Drosophila mutants defective in pavlovian olfactory memory have provided unique insight into the molecular basis of memory storage. Occasionally, these singular genetic lesions have been assembled into meaningful molecular pathways and neural circuitries. For the most part, however, these genes and their expression patterns in the CNS remain fragmented, demanding new clues from continued mutant screens. From a behavioral screen for long-term memory (LTM) mutants, we have identified ben (CG32594), which encodes a novel protein. Mutations of ben specifically disrupt LTM, leaving earlier memory phases intact. The role of ben appears physiological rather than developmental, because acutely induced expression of a ben+ transgene in adults rescues the mutant’s LTM defect. More interestingly, induced expression of ben+ specifically in mushroom bodies (MBs), but not in the ellipsoid body of the central complex, is sufficient to rescue the mutant LTM defect. This suggests a role for ben in the MB during olfactory memory formation. We also provide evidence that BEN interacts genetically in both synaptic transmission and LTM formation with SCAMP, a synaptic protein known to be involved in vesicle recycling.
olfactory learning; synaptic transmission mutants; larval neuromuscular junction; mutant; learning and memory; neurotransmission