Background. Cancer/testis antigens (CTAs) are ideal targets for cancer immunotherapy in virtue of their restricted expression profile in normal tissues. However, CTA-targeted immunotherapy has been rather disappointing clinical setting for CTAs are downregulated by cytosine-phosphate-guanosine (CpG) methylation in their promoter regions, so that tumor cells have low immunogenicity. Methods. We reinduced mouse CTA P1A through demethylation process and generated P1A-specific cytotoxic lymphocytes (CTLs) by immunizing BALB/c (H-2d) mice with dendritic cells pulsed with a P1A-specific peptide and CpG oligodeoxynucleotide (ODN) immune adjuvant. Results. We found that demethylation and CpG ODN immune adjuvant stimulation facilitated DC maturation and enhanced the allogenic capacity of P1A-specific CTLs against target cells both in vitro and in vivo. Conclusions. Our results suggested that CTA induction and immune adjuvant stimulation is a feasible strategy in cancer immunotherapy.
Adding propagules (source) to a degraded site (recipient) is a common way of manipulating secondary succession to restore diversity and services formerly provided by forests. However, heretofore no study has considered the effect of “successional distance” between source and recipient site. Four sites in the Shilin karst area of SW China were treated as different states along a secondary successional sere: grass, shrub, young secondary forest, and primary forest. Ten 1 m ×1m soil quadrats in the grass, shrub and young forest sites were replaced with 10 cm deep soil sources from corresponding later successional stage(s) in January 2009. Woody plant seed germination was monitored in the first year and seedling survival was monitored until the end of the second year. At the end of 2010, 2097 seeds of woody plants belonging to 45 taxa had germinated, and 3.9% of the seedlings and 7.8% of the species survived. Germination of most species was sensitive to ambient light (red, far-red, R:FR ratios, photosynthetically active radiation). Soil source and recipient site had a significant effect on the total number of seeds and number of species that germinated, and on the percentage of seedlings that survived through the end of the second year. Closer successional stages between recipient site and soil source had higher seed germination and seedling-survival percentages. However, a transition threshold exists in the young forest state, where seeds can germinate but not survive the second year. Our results, although based on an unreplicated chronosequence, suggest that successional distance between soil sources and recipient sites affect forest recruitment and restoration in degraded karst of SW China.
Association studies have been employed to investigate the relationships between host single nucleotide polymorphisms (SNPs) and susceptibility to pulmonary Tuberculosis (PTB). However, such candidate genetic markers have not been widely studied in Chinese population, especially with respect to the disease development from latent M. tuberculosis infection (LTBI).
In this case–control study, 44 candidate SNPs were examined in a total of 600 participants (PTB patients, LTBI controls and healthy controls without M. tuberculosis infection) from Zhengzhou, China. The two groups of controls were frequency matched on gender and age with PTB patients. Genotyping was carried out by the Illumina Golden Gate assay.
When comparing PTB patients with LTBI controls but not healthy controls without M. tuberculosis infection, significant associations with disease development were observed for TLR9 1174 A/G, TLR9 1635 A/G and IFNG 2109G/A. The two loci in TLR9 were in LD in our study population (r2=0.96, D’=1.00). A combined effect of the genotypes associated with increased risk of PTB (i.e. TLR9 1174G/G and IFNG 2109 A/A) was found when comparing PTB patients with LTBI controls (p=0.004) but not with healthy controls without infection (p=0.433).
Potential associations between TLR9 and IFN-γ genetic polymorphisms and PTB were observed in a Chinese population which supports further study of the roles played by TLR9/IFN-γ pathway during the development of PTB.
Pulmonary tuberculosis; TLR9; IFN-γ; Genetic polymorphisms; Susceptibility; Chinese
N-Myc downstream-regulated gene 2 (NDRG2) is a candidate tumor suppressor gene, which plays an important role in controlling tumor growth. The aim of this study was to investigate the expression of NDRG2 gene in bladder cancer (BC) tissues and several bladder cancer cell lines, and to seek its clinical and pathological significance. Ninety-seven bladder carcinoma and 15 normal bladder tissue sections were analyzed retrospectively with immunohistochemistry. The human bladder cancer cell line T24 was infected with LEN-NDRG2 or LEN-LacZ. The effects of NDRG2 overexpression on T24 cells and T24 nude mouse xenografts were measured via cell growth curves, tumor growth curves, flow cytometric analysis, western blot and Transwell assay. NDRG2 was highly expressed in normal bladder tissue, but absent or rarely expressed in cacinomatous tissues (χ2=8.761, p < 0.01). The NDRG2 level was negatively correlated with tumor grade and pathologic stage(r=-0.248, p < 0.05), as well as increased c-myc level (r=-0.454, p< 0.001). The expression of NDRG2 was low in the three BC cell lines. T24 cells infected with LEN-NDRG2 showed inhibition of proliferation both in vitro and in vivo, and NDRG2 overexpression can inhibit tumor growth and invasion in vitro.
To determine prevalence, genotypes and predictors of anal human papillomavirus (HPV) among HIV-infected and uninfected men who have sex with men (MSM) in Beijing, China. In 2010–2011, we recruited MSM (age range 18–61; median 28 years) through peer volunteers, and collected demographic/behavioral information via interviewer-administrated questionnaires. Trained health workers collected anal swabs for HPV genotyping by PCR and blood samples for HIV/syphilis serologies . We obtained anal specimens from 212 HIV-infected and 459 HIV-uninfected participants. Among HIV-infected MSM, 82.1% were HPV-infected vs. 57.5% in HIV-uninfected (p<0.01). HIV-infected men had the greatest likelihood of multiple types: 17.9% uninfected; 36.3% with one type; 36.8% with 2–3; 9.0% with >4. Oncogenic HPV prevalence was higher among HIV- infected (61.3%) than uninfected participants (39.7%; p<0.01). HIV-uninfected MSM reporting always using condoms during insertive anal intercourse (past 6 months) were less likely to be HPV-infected (OR=0.49, 95%CI: 0.31–0.77). Among HIV-uninfected MSM, HPV infection was associated with unprotected receptive anal intercourse (past 6 months; OR=1.92, 95%CI: 1.19–3.11) and being forced to have sex (previous year; OR=3.32, 95%CI: 1.10–10.0). Multivariable logistic analysis among HIV infected MSM suggested that unprotected oral intercourse (past 6 months) was associated with HPV (adjusted OR=2.12, 95%CI: 1.00–4.48). Syphilis occurred in 55.8% of HIV-infected/HPV-infected, 50.0% of HIV-infected/HPV-uninfected, 19.6% of HIV-uninfected/HPV-infected, and 13.0% of HIV-uninfected/HPV-uninfected MSM. HPV anal infections were more common among HIV-infected than uninfected MSM in China, including oncogenic and multiple types. Unprotected oral and receptive anal sex were significant HPV risk factors. Promotion of safer sex and HPV vaccination is strongly recommended among MSM.
Human papillomavirus; HIV; syphilis; genotype; men who have sex with men; China
MicroRNAs (miRNAs) are short RNAs with essential roles in gene regulation in various organisms including higher plants. In contrast to the vast information on miRNAs from many economically important plants, almost nothing has been reported on the identification or analysis of miRNAs from rubber tree (Hevea brasiliensis L.), the most important natural rubber-producing crop. To identify miRNAs and their target genes in rubber tree, high throughput sequencing combined with a computational approach was performed. Four small RNA libraries were constructed for deep sequencing from mature and young leaves of two rubber tree clones, PB 260 and PB 217, which provide high and low latex yield, respectively. 115 miRNAs belonging to 56 known miRNA families were identified, and northern hybridization validated miRNA expression and revealed developmental stage-dependent and clone-specific expression for some miRNAs. We took advantage of the newly released rubber tree genome assembly and predicted 20 novel miRNAs. Further computational analysis uncovered potential targets of the known and novel miRNAs. Predicted target genes included not only transcription factors but also genes involved in various biological processes including stress responses, primary and secondary metabolism, and signal transduction. In particular, genes with roles in rubber biosynthesis are predicted targets of miRNAs. This study provides a basic catalog of miRNAs and their targets in rubber tree to facilitate future improvement and exploitation of rubber tree.
miRNAs; Rubber tree; miR396; miR172; Rubber elongation factor; Hevamine A
Human papillomavirus (HPV) is the principal cause of invasive cervical cancer and benign genital lesions. There are currently 30 HPV types linked to cervical cancer. HPV infection also leads to other types of cancer. We developed a 61-plex analysis of these 30 HPV types by examining two genes, E6 and L1, using MassARRAY matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) (PCR-MS). Two hundred samples from homosexual males (HM) were screened by PCR-MS and MY09/MY11 primer set-mediated PCR (MY-PCR) followed by sequencing. One hundred thirty-five formalin-fixed, paraffin-embedded (FFPE) cervical cancer samples were also analyzed by PCR-MS, and results were compared to those of the commercially available GenoArray (GA) assay. One or more HPV types were identified in 64.5% (129/200) of the samples from HM. Comprising all 30 HPV types, PCR-MS detected 51.9% (67/129) of samples with multiple HPV types, whereas MY-PCR detected only one single HPV type in these samples. All PCR-MS results were confirmed by MY-PCR. In the cervical cancer samples, PCR-MS and GA detected 97% (131/135) and 90.4% (122/135) of HPV-positive samples, respectively. PCR-MS and GA results were fully concordant for 122 positive and 4 negative samples. The sequencing results for the 9 samples that tested negative by GA were completely concordant with the positive PCR-MS results. Multiple HPV types were identified in 25.2% (34/135) and 55.6% (75/135) of the cervical cancer samples by GA and PCR-MS, respectively, and results were confirmed by sequencing. The new assay allows the genotyping of >1,000 samples per day. It provides a good alternative to current methods, especially for large-scale investigations of multiple HPV infections and degraded FFPE samples.
The purpose of this study was to investigate the role of activated Rho GTPase cell division control protein 42 homolog (Cdc42) in colorectal cancer cell adhesion, migration, and invasion.
The constitutively active form of Cdc42 (GFP-Cdc42L61) or control vector was overexpressed in the colorectal cancer cell line SW480. The localization of active Cdc42 was monitored by immunofluorescence staining, and the effects of active Cdc42 on cell migration and invasion were examined using an attachment assay, a wound healing assay, and a Matrigel migration assay in vitro.
Immunofluorescence staining revealed that constitutively active Cdc42 predominately localized to the plasma membrane. Compared to SW480 cells transfected with the control vector, overexpression of constitutively active Cdc42 in SW480 cells promoted filopodia formation and cell stretch and dramatically enhanced cell adhesion to the coated plates. The wound healing assay revealed a significant increase of migration capability in SW480 cells expressing active Cdc42 compared to the control cells. Additionally, the Matrigel invasion assay demonstrated that active Cdc42 significantly promoted SW480 cell migration through the chamber.
Our results suggest that active Rho GTPase Cdc42 can greatly enhance colorectal cancer cell SW480 to spread, migrate, and invade, which may contribute to colorectal cancer metastasis.
Rho GTPase Cdc42; colorectal cancer; cell invasion; cell migration
Visual environment plays an important role in the occurrence of myopia. We previously showed that the different flashing lights could result in distinct effects on the ocular growth and development of myopia. CCN2 has been reported to regulate various cellular functions and biological processes. However, whether CCN2 signaling was involved in the red flashing light-induced myopia still remains unknown. In the present study, we investigated the effects of the red flashing lights exposure on the refraction and axial length of the eyes in vivo and then evaluated their effects on the expression of CCN2 and TGF-β in sclera tissues. Our data showed that the eyes exposed to the red flashing light became more myopic with a significant increase of the axial length and decrease of the refraction. Both CCN2 and TGF-β, as well as p38 MAPK and PI3K, were highly expressed in the sclera tissues exposed to the red flashing light. Both CCN2 and TGF-β were found to have the same gene expression profile in vivo. In conclusion, our findings found that CCN2 signaling pathway plays an important role in the red flashing light-induced myopia in vivo. Moreover, our study establishes a useful animal model for experimental myopia research.
It is now recognized that transplantation of bone marrow cells (BMCs) into infarcted hearts has the capacity to improve the cardiac function through paracrine effects. However, detailed expression levels of paracrine factors in BMCs in infarcted hearts are poorly described. By use of laser capture microdissection combined with real-time PCR, we depicted the expression profiles of paracrine factors in infarcted hearts versus normal hearts. Consistent with the in vivo observation, a similar expression pattern was evidenced in cultured BMCs. Furthermore, BMCs displayed heterogeneity of paracrine effects in infarcted hearts as analyzed at the single cell level using single cell PCR. Interestingly, the CD45+ subpopulation showed higher expression levels of angiogenic factors compared to other subpopulations. Finally, most angiogenic factors were induced under the microenvironment of infarction. Our study demonstrated the heterogeneity of paracrine effects in BMCs at single cell level in infarcted hearts, highlighting preferential expression of angiogenic factors in the CD45+ subpopulation. These findings broaden our understanding of paracrine effects of BMCs in vivo, and offer new insights into BMCs therapy in myocardial infarction (MI).
Previous studies have shown that core leptosporangiates, the most species-rich group of extant ferns (monilophytes), have a distinct plastid genome (plastome) organization pattern from basal fern lineages. However, the details of genome structure transformation from ancestral ferns to core leptosporangiates remain unclear because of limited plastome data available. Here, we have determined the complete chloroplast genome sequences of Lygodium japonicum (Lygodiaceae), a member of schizaeoid ferns (Schizaeales), and Marsilea crenata (Marsileaceae), a representative of heterosporous ferns (Salviniales). The two species represent the sister and the basal lineages of core leptosporangiates, respectively, for which the plastome sequences are currently unavailable. Comparative genomic analysis of all sequenced fern plastomes reveals that the gene order of L. japonicum plastome occupies an intermediate position between that of basal ferns and core leptosporangiates. The two exons of the fern ndhB gene have a unique pattern of intragenic copy number variances. Specifically, the substitution rate heterogeneity between the two exons is congruent with their copy number changes, confirming the constraint role that inverted repeats may play on the substitution rate of chloroplast gene sequences.
chloroplast genome; core leptosporangiates; schizaeoid ferns; heterosporous ferns; ndhB; intragenic rate heterogeneity
Recent genetic association studies have implicated several candidate susceptibility variants for schizophrenia among general populations. Rs1344706, an intronic SNP within ZNF804A, was identified as one of the most compelling candidate risk SNPs for schizophrenia in Europeans through genome-wide association studies (GWASs) and replications as well as large-scale meta-analyses. However, in Han Chinese, the results for rs1344706 are inconsistent, and whether rs1344706 is an authentic risk SNP for schizophrenia in Han Chinese is inconclusive. Here, we conducted a systematic meta-analysis of rs1344706 with schizophrenia in Chinese population by combining all available case-control samples (N = 12), including a total of 8,982 cases and 12,342 controls. The results of our meta-analysis were not able to confirm an association of rs1344706 A-allele with schizophrenia (p = 0.10, odds ratio = 1.06, 95% confidence interval = 0.99–1.13). Such absence of association was further confirmed by the non-superiority test (p = 0.0003), suggesting that rs1344706 is not a risk SNP for schizophrenia in Han Chinese. Detailed examinations of individual samples revealed potential sampling bias in previous replication studies in Han Chinese. The absence of rs1344706 association in Han Chinese suggest a potential genetic heterogeneity in the susceptibility of schizophrenia on this locus and also demonstrate the difficulties in replicating genome-wide association findings of schizophrenia across different ethnic populations.
Stromal cells and mesenchymal stem cells (MSCs), 2 important cell populations within the hematopoietic microenvironment, may play an important role in the development of hematopoietic stem/progenitor cells. We have successfully cultured human umbilical cord blood-derived stromal cells (hUCBDSCs). It has been demonstrated that MSCs also exist in hUCB. However, we have not found any reports on the distinct characteristics of hUCBDSCs and human umbilical cord blood-derived mesenchymal stem cells (hUCBDMSCs). In this study, hUCBDSCs and hUCBDMSCs were isolated from the cord blood of full-term infants using the same density gradient centrifugation and cultured in the appropriate medium. Some biological characteristics and hematopoietic supportive functions were compared in vitro. hUCBDSCs were distinct from hUCBDMSCs in morphology, proliferation, cell cycle, passage, immunophenotype, and the capacity for classical tri-lineage differentiation. Finally, quantitative real-time polymerase chain reaction analysis revealed that granulocyte colony-stimulating factor (G-CSF) gene expression was higher in hUCBDSCs than that in hUCBDMSCs. Enzyme-linked immunosorbent assay revealed that the secretion of G-CSF, thrombopoietin (TPO), and granulocyte macrophage colony-stimulating factor (GM-CSF) by hUCBDSCs was higher than that by hUCBDMSCs. After coculture, the granulocyte/macrophage colony-forming units (CFU-GM) of hematopoietic cells from the hUCBDSC feeder layer was more than that from the hUCBDMSC feeder layer. Flow cytometry was used to detect CD34+ hematopoietic stem/progenitor cell committed differentiation during 14 days of coculture; the results demonstrated that CD14 and CD33 expression in hUCBDSCs was significantly higher than their expression in hUCBDMSCs. This observation was also true for the granulocyte lineage marker, CD15. This marker was expressed beginning at day 7 in hUCBDSCs. It was expressed earlier and at a higher level in hUCBDSCs compared with hUCBDMSCs. In conclusion, hUCBDSCs are different from hUCBDMSCs. hUCBDSCs are superior to hUCBDMSCs in supporting hematopoiesis stem/progenitor cells differentiation into myeloid lineage cells at an early stage in vitro.
To determine prevalence of genital human papillomavirus (HPV) infection among men in rural China, we analyzed genital swab specimens. Among 2,236 male residents of rural Henan Province, HPV infection prevalence was 17.5%. The most common oncogenic and nononcogenic types were HPV-16 and HPV-3, respectively. Infection was associated with younger age and multiple sex partners.
HPV; men; China; viruses; genital infection; human papillomavirus
Men who have sex with men (MSM) were found to be one of the high-risk populations for Entamoeba histolytica (E. histolytica) infection. Accompanied by the prevalence of human immunodeficiency virus (HIV) among MSM, invasive amebiasis caused by E. histolytica has been paid attention to as an opportunistic parasitic infection. However, the status of E. histolytica infection among MSM has been barely studied in mainland China.
Seroprevalance of E. histolytica was determined using an enzyme-linked immunosorbent assay based on a cross-sectional study conducted in Beijing and Tianjin, China. Factors potentially associated with E. histolytica infection were identified by logistic regression analysis.
A total of 602 MSM were included in the study and the laboratory data on serostatus of E. histolytica were available for 599 of them (99.5%). 246 (41.1%) and 51 (8.5%) of the study participants were E. histolytica seropositive and HIV seropositive, respectively. Univariate analyses suggested preferred anal sex behaviors were associated with E. histolytica seropositivity. In multivariate logistic regression analysis, “only has receptive anal sex” (OR: 2.03; 95% CI: 1.22 3.37), “majority receptive anal sex” (OR: 1.83; 95% CI: 1.13, 2.95), and “sadomasochistic behavior (SM)” (OR: 2.30; 95% CI: 1.04, 5.13) were found to be significantly associated with E. histolytica infection.
High seroprevalence of E. histolytica infection was observed among MSM from Beijing and Tianjin, China. Receptive anal sex behavior and SM were identified as potential predictors. Therefore, E. histolytica and HIV co-infection needs to be concerned among MSM due to their sharing the common risk behaviors.
Entamoeba histolytica (E. histolytica) is a very common human gastrointestinal parasitic disease which affects 50 million people worldwide. Men who have sex with men (MSM) have already been found to be one of the high-risk populations with E. histolytica infection. Previous studies have reported an increased risk for E. histolytica infection and invasive amebiasis in HIV seropositive MSM. This pilot study aimed to investigate the serology of E. histolytica among MSM from mainland China. High prevalence of E. histolytica infection (41.1%, 246/599) was observed among the study population, receptive anal sex behavior and sadomasochistic behavior were found to be associated with the E. histolytica serostatus. Although HIV infection was not found to be associated with E. histolytica infection in this pilot study, studies from other countries had reported increased risks for E. histolytica infection and invasive amebiasis among HIV-positive MSM. Our findings suggest E. histolytica infection control needs to be concerned with respect to the increasing HIV prevalence among Chinese MSM population.
This report describes the design and application of several distinct gold-containing indoles as anti-cancer agents. When used individually, all gold-bearing compounds display cytostatic effects against leukemia and adherent cancer cell lines. However, two gold-bearing indoles show unique behavior by increasing the cytotoxic effects of clinically relevant levels of ionizing radiation. Quantifying the amount of DNA damage demonstrates that each gold-indole enhances apoptosis by inhibiting DNA repair. Both Au(I)-indoles were tested for inhibitory effects against various cellular targets including thioredoxin reductase, a known target of several gold compounds, and various ATP-dependent kinases. While neither compound significantly inhibits the activity of thioreoxin reductase, both showed inhibitory effects against several kinases associated with cancer initiation and progression. The inhibition of these kinases provides a possible mechanism for the ability of these Au(I)-indoles potentiate the cytotoxic effects of ionizing radiation. Clinical applications of combining Au(I)-indoles with ionizing radiation are discussed as a new strategy to achieve chemosensitization of cancer cells.
Gold; indoles; chemotherapy; radiosensitizing agents; apoptosis
Adenomatous polyposis coli (APC) regulates cell-cell adhesion and cell migration through activating the APC-stimulated guanine nucleotide-exchange factor (GEF; Asef), which is usually autoinhibited through the binding between its Src homology 3 (SH3) and Dbl homology (DH) domains. The APC-activated Asef stimulates the small GTPase Cdc42, which leads to decreased cell-cell adherence and enhanced cell migration. In colorectal cancers, truncated APC constitutively activates Asef and promotes cancer cell migration and angiogenesis. Here, we report crystal structures of the human APC/Asef complex. We find that the armadillo repeat domain of APC uses a highly conserved surface groove to recognize the APC-binding region (ABR) of Asef, conformation of which changes dramatically upon binding to APC. Key residues on APC and Asef for the complex formation were mutated and their importance was demonstrated by binding and activity assays. Structural superimposition of the APC/Asef complex with autoinhibited Asef suggests that the binding between APC and Asef might create a steric clash between Asef-DH domain and APC, which possibly leads to a conformational change in Asef that stimulates its GEF activity. Our structures thus elucidate the molecular mechanism of Asef recognition by APC, as well as provide a potential target for pharmaceutical intervention against cancers.
APC; Asef; cell adhesion and cell migration; cancer; armadillo repeat domain
Genetic polymorphism is suggested to be associated with human physical performance. The angiotensin I-converting enzyme insertion/deletion (ACE I/D) polymorphism and the α-actinin-3 gene (ACTN3) R577X polymorphism have been most widely studied for such association analysis. However, the findings are frequently heterogeneous. We aim to summarize the associations of ACE I/D and ACTN3 R577X with sport performance by means of meta-analysis.
We systematically reviewed and quantitatively summarized published studies, until October 31, 2012, on relationship between ACE/ACTN3 genetic polymorphisms and sports performance, respectively.
A total of 366 articles on ACE and 88 articles on ACTN3 were achieved by literature search. A significant association was found for ACE II genotype compared to D allele carriage (DD+ID) with increased possibility of physical performance (OR, 1.23; 95% CI, 1.05–1.45). With respect to sport discipline, the II genotype was found to be associated with performance in endurance athletes (OR, 1.35; 95% CI, 1.17–1.55). On the other hand, no significant association was observed for ACTN3 RR genotype as compared to X allele carriage (XX+RX) (OR, 1.03; 95% CI, 0.92–1.15). However, when restricted the analyses to power events, a significant association was observed (OR, 1.21; 95% CI, 1.03–1.42).
Our results provide more solid evidence for the associations between ACE II genotype and endurance events and between ACTN3 R allele and power events. The findings suggest that the genetic profiles might influence human physical performance.
Biological invasions are predicted to be more frequent as climate change is increasing its positive impact on the prevalence of invasive exotic species. Success of insect invaders in different temperature zones is closely related to their tolerance to temperature extremes. In this study, we used an exotic lace bug (Corythucha ciliata) as the study organism to address the hypotheses that an insect species invading a subtropical zone from temperate regions has a high capacity to survive and adapt to high temperatures, and that its thermal tolerance plays an important role in determining its seasonal abundance and geographic distribution. To test these hypotheses, the effects of heat shock on the survival and reproduction of C. ciliata adults were assessed in the laboratory. Adults were exposed to 26 (control), 35, 37, 39, 41, 43, and 45°C for 2 h, and then were transferred to 26°C. Heat-shock temperatures ranging from 35 to 41°C did not significantly affect survival pattern, longevity, and fecundity of adults, but heat shock at 43 and 45°C significantly reduced these traits. Exposing parent females to heat-shock treatments from 35 to 41°C did not significantly affect the hatching rate of their eggs, survival of the nymphs, and the proportion of female F1 progeny, while no progeny were produced with treatments of 43 and 45°C. The results indicate that C. ciliata can tolerate high temperatures less than 41°C, which may contribute to its expansion into the lower latitudes in China where its hosts (Platanus trees) are widely planted. Our findings have important implications for predicting seasonal abundance and understanding invasion mechanisms of this important urban invader under climate change.
To compare long-term prognosis between complete revascularization (CR) and incomplete revascularization (IR) in elderly patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI).
We prospectively enrolled patients ≥ 75 years with ACS and multi-lesion disease between January 2005 and December 2010 at our center (Institute of Geriatric Cardiology, Chinese PLA General Hospital). Baseline clinical characteristics, PCI parameters and long-term (12 to 78 months) outcomes including main adverse cardiac and cerebral events (MACCE) were compared between CR and IR groups. We used the Kaplan-Meier curve to describe the survival rates, and variables reported to be associated with prognosis were included in Cox regression.
Of the 502 patients, 230 patients obtained CR, and the other 272 patients underwent IR. Higher SYNTAX score was an independent predictor of IR [Odds ratio (OR): 1.141, 95% confidence interval (95% CI): 1.066–1.221, P = 0.000]. A total of 429 patients (85.5%) were followed with a duration ranging from 12 months to 78 months. There were no significant differences in cumulative survival rates and event free survival rates between the two groups, even for patients with multi-vessel disease. Older age (OR: 1.079, 95% CI: 1.007–1.157, P = 0.032), prior myocardial infarction (OR: 1.440, 95% CI: 1.268–2.723, P = 0.001) and hypertension (OR: 1. 653, 95% CI: 1.010-2.734, P = 0.050) were significant independent predictors of long-term MACCE.
Given that both clinical and coronary lesion characteristics are much more complex in patients ≥75 years with ACS and multi-lesion disease, IR may be an option allowing low risk hospital results and meaningful long-term (12 to 78 months) outcomes.
Elderly patients; Percutaneous Coronary Intervention; Incomplete Revascularization; Long-term Prognosis
To assess the secular trends in the etiology and comorbidity of patients hospitalized with congestive heart failure (CHF).
Data of 7,319 patients (mean age 59.6 years, 62.1% male) with a primary discharge diagnosis of CHF, hospitalized from January 1, 1993 to December 31, 2007 at the Chinese People's Liberation Army (PLA) General Hospital were extracted and analyzed. These patients were divided into three groups according to hospitalization period: 1993–1997 (n = 1623), 1998–2002 (n = 2444), and 2003–2007 (n = 3252). The etiological characteristics and comorbidities were assessed.
Over the study period, the proportion of patients with ischemic heart disease (IHD) increased from 37.2% during the period 1993–1997 to 46.8% during the period 2003–2007, while that with valvular heart disease (VHD) decreased from 35.2% during the period 1993–1997 to 16.6% during the period 2003–2007 (both P < 0.05). Atrial fibrillation (AF) was the most common comorbidity of heart failure (23.2%, 23.0% and 20.6%, respectively, in the three periods). Compared to that of the period of 1993–1997 with that of, the proportion of patients with myocardial infarction, pneumonia, renal function impairment and hepatic cirrhosis of the period of 2003–2007 increased significantly (P < 0.05) and the proportion of patients with chronic obstructive pulmonary disease and atrial fibrillation decreased significantly (P < 0.05).
This study implies that IHD has became a more common etiology of CHF, while VHD has deceased as an etiology of CHF in Chinese patients during the last two decades.
Atrial fibrillation; Congestive heart failure; Comorbidity; Etiology; Hospitalization
Saitohin (STH) is a gene unique to humans and their closest relatives whose function is not yet known. STH contains a single polymorphism (Q7R); the Q allele is human-specific and confers susceptibility to several neurodegenerative diseases. In previous work, we discovered that STH interacts with Peroxiredoxin 6 (Prdx6), a unique member of that family which is bifunctional and whose levels increase in Pick’s disease. In this study, we report that STH also interacts with tau and the non-receptor tyrosine kinase c-Abl (Abl). Furthermore, Abl phosphorylates STH on its single tyrosine residue and STH increases tyrosine phosphorylation by Abl. The effect of Saitohin on Abl-mediated phosphorylation appears to be allele-specific, providing evidence for a new cellular function for STH.
Saitohin interactions; primate-specific gene; human-specific allele; MAP tau; tyrosine kinase Abl; allele-specific effects; neurodegeneration
The interleukin-6 (IL-6) pathway is one of the mechanisms that link inflammation and angiogenesis with malignancy. Since nuclear factor-κB (NF-κB) is a potential sign for inflammation, NF-κB has been associated with the progression of disease in various types of cancer. In the present study, we investigated the effect of NF-κB on the IL-6 pathway in gastric carcinoma and their correlation with disease status and prognosis. The mRNA and protein levels of NF-κB, IL-6 and vascular endothelial growth factor (VEGF) were detected by western blotting and reverse transcription (RT) quantitative PCR (RT-qPCR). Using immunohistochemistry, we examined the expression of these proteins in normal and human gastric cancer tissue samples. The concentrations of IL-6 and TNF-α in collected blood samples were measured according to the enzyme-linked immunosorbent assay (ELISA). IL-6 and TNF-α were found to be expressed at high levels in human gastric cancer samples. A positive correlation was found between the expression of IL-6 and NF-κB by immunohistochemical and further correlation analysis. IL-6, NF-κB and VEGF protein and mRNA levels increased significantly in gastric cancer tissue compared with those in adjacent normal mucosa tissue samples. In conclusion, our findings demonstrate that NF-κB, IL-6 and VEGF mRNA and protein levels increase significantly in gastric cancer tissues. In addition, the expression of NF-κB was positively correlated with the expression of IL-6 according to immunohistochemical and further correlation analysis, which suggests that the suppression of NF-κB or IL-6 may be a potential target for clinical therapy of gastric cancer in the future.
gastric cancer; interleukin-6; nuclear factor-κB; vascular endothelial growth factor
Tau is a neuronal-specific microtubule-associated protein that plays an important role in establishing neuronal polarity and maintaining the axonal cytoskeleton. Aggregated tau is the major component of neurofibrillary tangles (NFTs), structures present in the brains of people affected by neurodegenerative diseases called tauopathies. Tauopathies include Alzheimer’s disease (AD), frontotemporal dementia with Parkinsonism (FTDP-17), the early onset dementia observed in Down syndrome (DS; trisomy 21) and the dementia component of myotonic dystrophy type 1 (DM1). Splicing misregulation of adult-specific exon 10, which codes for a microtubule binding domain, results in expression of abnormal ratios of tau isoforms, leading to FTDP-17. Positions 3 to 19 of the intron downstream of exon 10 define a hotspot of splicing regulation: the region diverges between humans and rodents, and point mutations within it result in tauopathies. In this study, we investigated three regulators of exon 10 splicing: serine/arginine-rich protein SRp75 and heterogeneous nuclear ribonucleoproteins hnRNPG and hnRNPE2. SRp75 and hnRNPG inhibit splicing of exon 10 whereas hnRNPE2 activates it. Using co-transfections, co-immunoprecipitations and RNAi we discovered that SRp75 binds to the proximal downstream intron of tau exon 10 at the FTDP-17 hotspot region; and that hnRNPG and hnRNPE2 interact with SRp75. Thus, increased exon 10 inclusion in FTDP mutants may arise from weakened SRp75 binding. This work provides insights into the splicing regulation of the tau gene and into possible strategies for correcting the imbalance in tauopathies caused by changes in the ratio of exon 10.
MAP tau; Exon 10 and tangle dementia; Isoform ratios; Alternative splicing regulation; Splicing factor SRp75; Heterogeneous nuclear ribonucleoproteins G and E2