Gender Differences in the Association of Smoking and Drinking with the Development of Cognitive Impairment

Modifiable lifestyle-related factors such as smoking and alcohol drinking are associated with cognitive impairment in the elderly population but the relationships have shown various results. To evaluate the relationship of alcohol drinking and smoking in the early 60 s with the risk of developing incident cognitive impairment. In 1999, we evaluated cognitive function, smoking, and drinking status in 3,174 inhabitants aged 60–64 years in a rural area of Korea, with a follow-up assessment of cognitive function 7 years later. A total of 1,810 individuals who did not show cognitive impairment at baseline were included. A stratified analysis was applied to evaluate how smoking and alcohol drinking affected the risk of developing cognitive impairment based on gender. Current smokers showed a higher risk for developing cognitive impairment than did never smokers (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.09–2.15). The OR for female current smokers compared with never smokers was 1.62 (95% CI, 1.05–2.52), and smokers with higher pack-years were more likely to develop cognitive impairment than never smokers, showing a dose–response relationship (P for trend = 0.004). Frequent alcohol consumption increased the risk of developing cognitive impairment (OR, 1.68; 95% CI, 1.01–2.78), and a dose–response relationship was observed among male subjects (P for trend = 0.044). Infrequent drinking in females decreased the odds of developing cognitive impairment (OR, 0.67; 95% CI, 0.42–1.00), whereas frequent drinking tended to increase the odds, although this trend was not significant, suggesting a U-shaped relationship. Although the sample was small for some analyses, especially in female, our data suggest that smoking and drinking in the early 60 s are associated with a risk of developing cognitive impairment, and this relationship is characterized by gender differences.     

Validity of Fecal Occult Blood Test in the National Cancer Screening Program,Korea

Aim

The aims of the current study were to assess the validity of the fecal occult blood test (FOBT) in an organized screening setting in Korea and to determine factors associated with FOBT validity, such as screening round, age group, and anatomical location of the cancer.

Methods

Study participants were those who were 50 years and older who received an FOBT through the National Cancer Screening Program between 2004 and 2007. Colorectal cancer diagnoses were ascertained through linkage with the Korean National Cancer Incidence Database. The positivity rate, colorectal cancer detection rate, interval cancer rate, sensitivity, specificity, and positive predictive value of the FOBT were calculated.

Results

A total of 2,193,093 tests were included in the analysis. Overall, the sensitivity of the FOBT for colorectal cancer was 59.7% for the first round and 56.1% for the subsequent round. Sensitivity was highest for distal colon cancer (65.9%) in the first round, and for rectal cancer (58.4%) for the subsequent round. The sensitivity and positive predictive value of the FOBT generally improved between 2004 and 2008.

Conclusions

The FOBT showed reasonable validity in an organized screening setting, and the validity of the FOBT varied by screening round, anatomical location, and screening year.     

Hypericin-photodynamic therapy leads to interleukin-6 secretion by HepG2 cells and their apoptosis via recruitment of BH3 interacting-domain death agonist and caspases

Photodynamic therapy (PDT) has emerged as a capable therapeutic modality for the treatment of cancer. PDT is a targeted cancer therapy that reportedly leads to tumor cell apoptosis and/or necrosis by facilitating the secretion of certain pro-inflammatory cytokines and expression of multiple apoptotic mediators in the tumor microenvironment. In addition, PDT also triggers oxidative stress that directs tumor cell killing and activation of inflammatory responses. However, the cellular and molecular mechanisms underlying the role of PDT in facilitating tumor cell apoptosis remain ambiguous. Here, we investigated the ability of PDT in association with hypericin (HY) to induce tumor cell apoptosis by facilitating the induction of reactive oxygen species (ROS) and secretion of Th1/Th2/Th17 cytokines in human hepatocellular liver carcinoma cell line (HepG2) cells. To discover if any apoptotic mediators were implicated in the enhancement of cell death of HY-PDT-treated tumor cells, selected gene profiling in response to HY-PDT treatment was implemented. Experimental results showed that interleukin (IL)-6 was significantly increased in all HY-PDT-treated cells, especially in 1 μg/ml HY-PDT, resulting in cell death. In addition, quantitative real-time PCR analysis revealed that the expression of apoptotic genes, such as BH3-interacting-domain death agonist (BID), cytochrome complex (CYT-C) and caspases (CASP3, 6, 7, 8 and 9) was remarkably higher in HY-PDT-treated HepG2 cells than the untreated HepG2 cells, entailing that tumor destruction of immune-mediated cell death occurs only in PDT-treated tumor cells. Hence, we showed that HY-PDT treatment induces apoptosis in HepG2 cells by facilitating cytotoxic ROS, and potentially recruits IL-6 and apoptosis mediators, providing additional hints for the existence of alternative mechanisms of anti-tumor immunity in hepatocellular carcinoma, which contribute to long-term suppression of tumor growth following PDT.     

Bioactive activities of natural products against herpesvirus infection

More than 90% of adults have been infected with at least one human herpesvirus, which establish long-term latent infection for the life of the host. While anti-viral drugs exist that limit herpesvirus replication, many of these are ineffective against latent infection. Moreover, drug-resistant strains of herpesvirus emerge following chemotherapeutic treatment. For example, resistance to acyclovir and related nucleoside analogues can occur when mutations arise in either HSV thymidine kinase or DNA polymerases. Thus, there exists an unmet medical need to develop new anti-herpesvirus agents with different mechanisms of action. In this Review, we discuss the promise of anti-herpetic substances derived from natural products including extracts and pure compounds from potential herbal medicines. One example is Glycyrrhizic acid isolated from licorice that shows promising antiviral activity towards human gammaherpesviruses. Secondly, we discuss anti-herpetic mechanisms utilized by several natural products in molecular level. While nucleoside analogues inhibit replicating herpesviruses in lytic replication, some natural products can disrupt the herpesvirus latent infection in the host cell. In addition, natural products can stimulate immune responses against herpesviral infection. These findings suggest that natural products could be one of the best choices for development of new treatments for latent herpesvirus infection, and may provide synergistic anti-viral activity when supplemented with nucleoside analogues. Therefore, it is important to identify which natural products are more efficacious anti-herpetic agents, and to understand the molecular mechanism in detail for further advance in the anti-viral therapies.     

CK2 inhibitor CX4945 induces sequential inactivation of proteins in the signaling pathways related with cell migration and suppresses metastasis of A549 human lung cancer cells

Casein kinase 2 (CK2) is known to be involved in various cellular processes such as cell cycle, apoptosis and proliferation. It has been reported that the inhibition of CK2 induced by recently developed small molecule CX4945 shows anti-cancer effects including anti-proliferation and anti-angiogenesis in several different cancers including prostate cancer. Here we report that migration and invasion of A549 human lung cancer cells are suppressed by the inhibition of CK2 induced by CX4945. We found that CX4945 sequentially attenuates the proteins in PI3K/Akt and MAPK pathways, two signaling pathways related with cell migration. This sequential control of signal pathways inhibits the expression of membrane type 1-matrix metalloproteinase and this leads to the selective attenuation of one of the gelatinases, MMP-2, which can degrade components of extracellular matrix, and metastasis of A549 human lung cancer cell.     

Multiple interactions of NaHER1 protein with abscisic acid signaling in Nicotiana attenuata plants

Previously, we identified a novel herbivore elicitor-regulated protein in Nicotiana attenuata (NaHER1) that is required to suppress abscisic acid (ABA) catabolism during herbivore attack and activate a full defense response against herbivores. ABA, in addition to its newly defined role in defense activation, mainly controls seed germination and stomatal function of land plants. Here we show that N. attenuata seeds silenced in the expression of NaHER1 by RNA interference (irHER1) accumulated less ABA during germination, and germinated faster on ABA-containing media compared to WT. Curiously, epidermal cells of irHER1 plants were wrinkled, possibly due to the previously demonstrated increase in transpiration of irHER1 plants that may affect turgor and cause wrinkling of the cells. We conclude that NaHER1 is a highly pleiotropic regulator of ABA responses in N. attenuata plants.     

Solid State Enabled Reversible Four Electron Storage

We report that a solid‐state battery architecture enables the reversible, four electron storage of fully utilized solvothermally synthesized cubic‐FeS₂ (pyrite). With a sulfide based glass electrolyte we successfully confine electro‐active species and permit the safe use of a lithium metal anode. These FeS₂/Li solid‐state cells deliver a theoretical specific capacity of 894 mAh g^?1 at 60 °C. We find that nanoparticles of orthorhombic‐FeS₂ (marcasite) are generated upon recharge at 30–60 °C which explains a coincident change in rate kinetics.     

Identification of human placenta‐derived mesenchymal stem cells involved in re‐endothelialization

Human placenta is an attractive source of mesenchymal stem cells (MSC) for regenerative medicine. The cell surface markers expressed on MSC have been proposed as useful tools for the isolation of MSC from other cell populations. However, the correlation between the expression of MSC markers and the ability to support tissue regeneration in vivo has not been well examined. Here, we established several MSC lines from human placenta and examined the expression of their cell surface markers and their ability to differentiate toward mesenchymal cell lineages. We found that the expression of CD349/frizzled‐9, a receptor for Wnt ligands, was positive in placenta‐derived MSC. So, we isolated CD349‐negative and ‐positive fractions from an MSC line and examined how successfully cell engraftment repaired fractured bone and recovered blood flow in ischemic regions using mouse models. CD349‐negative and ‐positive cells displayed a similar expression pattern of cell surface markers and facilitated the repair of fractured bone in transplantation experiments in mice. Interestingly, CD349‐negative, but not CD349‐positive cells, showed significant effects on recovering blood flow following vascular occlusion. We found that induction of PDGFβ and bFGF mRNAs by hypoxia was greater in CD349‐negative cells than in CD349‐positive cells while the expression of VEGF was not significantly different in CD349‐negative and CD349‐positive cells. These findings suggest the possibility that CD349 could be utilized as a specialized marker for MSC isolation for re‐endothelialization. J. Cell. Physiol. 226: 224–235, 2010. © 2010 Wiley‐Liss, Inc.