• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.sup3
• /
• pp.119-123
• /
• 2016

Thyroid cancer, the most common endocrine neoplasia, consists of four main types of carcinomas: papillary, follicular, and anaplastic, all with thyroid follicular origin, and medullary thyroid cancer (MTC) related to para-follicular cells. Cronic diseases such as diverse cancers may be associated with cachexia, especially at advanced stage. Cancer-induced cachexia is associated with diminished quality of life, functional performance, reduced response to antitumor therapy, and increased morbidity and mortality. Myostatin (Mst) is one of the outstanding molecules in the skeletal muscle loss process in cancer and it may be released by both skeletal muscle and cachexia-inducing tumors. Recently changes in serum levels of Mst have been identified as an important factor of cancer-induced cachexia. The goal of this study was to assessserum Mst levels in MTC patients. In this descriptive and case-control study, 90 participants were selected, comprising 45 MTC patients (20 males, $29{\pm}13.9years$, 25 females, $29{\pm}14.5years$) and 45 control individuals (25 males, $23.1{\pm}11.6years$, 20 females, $31.5{\pm}14.4years$). Serum Mst was determined using an ELISA kit and body mass index (BMI) was calculated by weight and height measurements. The Kolmogorov Simonov test showed a normal distribution for log transformed Mst serum levels in both case and control groups. Geometric means were 5.9 and 8.2 ng/ml respectively, and a significant difference was found according to the independent t-test results (P<0.01). There was also a significant difference mean of Mst between females in control and MTC groups, but not for the males. Pearson correlation test showed no correlation between age and BMI with Mst serum levels. The findings of this study support the hypothesis that Mst serum levels may have a potential ability for early diagnosis of cachexia in MTC patients, especially in females.

• BMB Reports
• /
• v.44 no.12
• /
• pp.793-798
• /
• 2011

Recently, pluripotency induction or cellular reprogramming by introducing critical transcription factors has been extensively studied, but has been demonstrated only in vitro. Based on reports that Oct4 is critically involved in transforming neural stem cells into pluripotent cells, we used the lentiviral vector to introduce the Oct4 gene into the hippocampal dentate gyrus (DG) of adult mice. We examined whether this manipulation led to cellular or behavioral changes, possibly through processes involving the transformation of NS cells into pluripotent cells. The Oct4 lentivirus-infused group and the green fluorescent protein lentivirus-infused group showed a similar thickness of the DG and a comparable level of synaptophysin expression in the DG. Furthermore, our behavioral analyses did not show any differences between the groups concerning exploratory activity, anxiety, or memory abilities. This first trial for pluripotency induction in vivo, despite negative results, provides implications and information for future studies on in vivo cellular reprogramming.

• Molecules and Cells
• /
• v.28 no.1
• /
• pp.37-42
• /
• 2009

Iron binding lactoferrin (Lf) is involved in the control of cell cycle progression. However, the molecular basis underlying the effects of Lf on cell cycle control, as well as its target genes, remains incompletely understood. In this study, we have demonstrated that a relatively low level of ironsaturated Lf, Lf($Fe^{3+}$), can stimulate S phase cell cycle entry, and requires Akt activation in MCF-7 cells. Lf($Fe^{3+}$) immediately induced Akt phosphorylation at Ser473, which subsequently induced the phosphorylation of two G1-checkpoint Cdk inhibitors, $p21^{Cip/WAF1}$ and $p27^{kip1}$. The Lf($Fe^{3+}$)-induced phosphorylation of Cdk inhibitors impaired their nuclear import behavior, thereby inducing cell cycle progression. However, the treatment of cells with a PI3K inhibitor, LY294002, almost completely blocked Lf($Fe^{3+}$)-stimulated cell cycle progression. LY294002 treatment abrogated Lf($Fe^{3+}$)-induced Akt activation, and prevented the cytoplasmic localization of $p27^{kip1}$. Higher levels of $p21^{Cip/WAF1}$ were also detected in the cytoplasmic sub-cellular compartment as a measure of cellular response to Lf($Fe^{3+}$). Consequently, the degree of phosphorylation of retinoblastoma protein was enhanced in response to Lf($Fe^{3+}$). Therefore, we conclude that Lf($Fe^{3+}$), as a potential antagonist of Cdk inhibitors, can facilitate the functions of E2F during progression to S phase via the Akt signaling pathway.

• Journal of Preventive Medicine and Public Health
• /
• v.37 no.4
• /
• pp.312-320
• /
• 2004

Objectives : An outbreak of acute hemorrhagic conjunctivitis (AHC) caused by coxsackie A24 (CA24) virus occurred in South Korea in 2002. CA24 was isolated for the first time from patients with AHC. Therefore, this study was conducted to understand the transmission routes and prevent another AHC outbreaks. Methods : The authors conducted a questionnaire survey among 1,730 students from 2 middle schools and 1 technical high school in Gyeongju city. For statistical analysis the chi-square test was used, and chi-square for trend method showing a level of significance less than p<0.05 was proven to be significant. Variables which were proven to be significant in univariate analysis were analysed by multiple logistic regression. Results : The attack rate was 57.1%. The student groups with rubbing one s own eyes, computer usage, and sharing cellular phone had a significantly higher AHC attack rate (p<0.05). According to the multiple logistic regression, the odds ratios for male, high school, computer use, sharing cellular phone, and rubbing one s own eyes were significant (p<0.05). Conclusion : The most significant feature of this outbreak was that many students rubbed their own eyes following contact with AHC patients in a deliberate attempt to avoid going to school. Other transmission methods were computer usage and sharing cellular phone. In the future, health and school authorities must plan new strategies for the prevention of AHC.

• Korean Journal of Veterinary Research
• /
• v.33 no.3
• /
• pp.407-417
• /
• 1993

Bupleurum falcatum has been used for treatment of inflammation, jaundice, influenza and hepatitis as a traditional orient folk medicine. This experiment was carried out to evaluate the effect of B falcatum extract on cellular immune responses in vivo and in vitro. Antigen binding cell(ABC) assay, antibody production, Arthus and delayed-type hypersensitivity(DTH) reaction against sheep erythrocytes(SRBC) were very depressed in B falcatum extract treated group in vivo. The growth of Staphylococcus aureus in brain heart infusion(BHI) broth containing B falcatum extract was remarkably inhibited. Otherwise, that of Salmonella typhyimurium was not significantly increased in vitro. When B falcatum extract pretreated mice were intraperitoneally(IP) injected S typhimurium and S aureus, respectively, the number of bacteria in peritoneal exudates were time dependent declination compared with those of control, and the weight of spleen and the number of macrophage migration into peritoneal cavity have no difference from those of untreated control. B falcatum extract gradually increased phagocytic activities of peritoneal macrophage against Candida albicans time and dose dependently, and was not significant production of migration inhibiotory factor(MIF). But migration abilities of normal leucocytes in B falcatum extract pretreated group were decreased dose dependently. When B falcatum extract was IP administered, these data indicate that B falcatum extract increases level of serum coticosterone. Therefore, B falcatum extract was indirectly mediated in immune system by serum coticosterone having relation to immunosuppression. These results lead to the conclusion that B falcatum extract acts as a trigger or regulator of cellular immune responses in immune system.

• KSII Transactions on Internet and Information Systems (TIIS)
• /
• v.11 no.11
• /
• pp.5301-5323
• /
• 2017

Small cell deployment offers a low-cost solution for the boosted traffic demand in heterogeneous cellular networks (HCNs). Besides improved spatial spectrum efficiency and energy efficiency, future HCNs are also featured with the trend of network architecture convergence and feasibility for flexible mobile applications. To achieve these goals, dual connectivity (DC) is playing a more and more important role to support control/user-plane splitting, which enables maintaining fixed control channel connections for reliability. In this paper, we develop a tractable framework for the downlink SINR analysis of DC assisted HCN. Based on stochastic geometry model, the data-control joint coverage probabilities under multi-frequency and single-frequency tiering are derived, which involve quick integrals and admit simple closed-forms in special cases. Monte Carlo simulations confirm the accuracy of the expressions. It is observed that the increase in mobility robustness of DC is at the price of control channel SINR degradation. This degradation severely worsens the joint coverage performance under single-frequency tiering, proving multi-frequency tiering a more feasible networking scheme to utilize the advantage of DC effectively. Moreover, the joint coverage probability can be maximized by adjusting the density ratio of small cell and macro cell eNBs under multi-frequency tiering, though changing cell association bias has little impact on the level of the maximal coverage performance.

• Molecules and Cells
• /
• v.44 no.2
• /
• pp.101-115
• /
• 2021

The INO80 chromatin remodeling complex has roles in many essential cellular processes, including DNA replication. However, the mechanisms that regulate INO80 in these processes remain largely unknown. We previously reported that the stability of Ino80, the catalytic ATPase subunit of INO80, is regulated by the ubiquitin proteasome system and that BRCA1-associated protein-1 (BAP1), a nuclear deubiquitinase with tumor suppressor activity, stabilizes Ino80 via deubiquitination and promotes replication fork progression. However, the E3 ubiquitin ligase that targets Ino80 for proteasomal degradation was unknown. Here, we identified the C-terminus of Hsp70-interacting protein (CHIP), the E3 ubiquitin ligase that functions in cooperation with Hsp70, as an Ino80-interacting protein. CHIP polyubiquitinates Ino80 in a manner dependent on Hsp70. Contrary to our expectation that CHIP degrades Ino80, CHIP instead stabilizes Ino80 by extending its half-life. The data suggest that CHIP stabilizes Ino80 by inhibiting degradative ubiquitination. We also show that CHIP works together with BAP1 to enhance the stabilization of Ino80, leading to its chromatin binding. Interestingly, both depletion and overexpression of CHIP compromise replication fork progression with little effect on fork stalling, as similarly observed for BAP1 and Ino80, indicating that an optimal cellular level of Ino80 is important for replication fork speed but not for replication stress suppression. This work therefore idenitifes CHIP as an E3 ubiquitin ligase that stabilizes Ino80 via nondegradative ubiquitination and suggests that CHIP and BAP1 act in concert to regulate Ino80 ubiquitination to fine-tune its stability for efficient DNA replication.

• BMB Reports
• /
• v.55 no.8
• /
• pp.370-379
• /
• 2022

Human pregnancy is a delicate and complex process where multiorgan interactions between two independent systems, the mother, and her fetus, maintain pregnancy. Intercellular interactions that can define homeostasis at the various cellular level between the two systems allow uninterrupted fetal growth and development until delivery. Interactions are needed for tissue remodeling during pregnancy at both fetal and maternal tissue layers. One of the mechanisms that help tissue remodeling is via cellular transitions where epithelial cells undergo a cyclic transition from epithelial to mesenchymal (EMT) and back from mesenchymal to epithelial (MET). Two major pregnancy-associated tissue systems that use EMT, and MET are the fetal membrane (amniochorion) amnion epithelial layer and cervical epithelial cells and will be reviewed here. EMT is often associated with localized inflammation, and it is a well-balanced process to facilitate tissue remodeling. Cyclic transition processes are important because a terminal state or the static state of EMT can cause accumulation of proinflammatory mesenchymal cells in the matrix regions of these tissues and increase localized inflammation that can cause tissue damage. Interactions that determine homeostasis are often controlled by both endocrine and paracrine mediators. Pregnancy maintenance hormone progesterone and its receptors are critical for maintaining the balance between EMT and MET. Increased intrauterine oxidative stress at term can force a static (terminal) EMT and increase inflammation that are physiologic processes that destabilize homeostasis that maintain pregnancy to promote labor and delivery of the fetus. However, conditions that can produce an untimely increase in EMT and inflammation can be pathologic. These tissue damages are often associated with adverse pregnancy complications such as preterm prelabor rupture of the membranes (pPROM) and spontaneous preterm birth (PTB). Therefore, an understanding of the biomolecular processes that maintain cyclic EMT-MET is critical to reducing the risk of pPROM and PTB. Extracellular vesicles (exosomes of 40-160 nm) that can carry various cargo are involved in cellular transitions as paracrine mediators. Exosomes can carry a variety of biomolecules as cargo. Studies specifically using exosomes from cells undergone EMT can carry a pro-inflammatory cargo and in a paracrine fashion can modify the neighboring tissue environment to cause enhancement of uterine inflammation.

• Environmental Mutagens and Carcinogens
• /
• v.23 no.2
• /
• pp.56-62
• /
• 2003

The liver progenitor cells could form a potential target cell population fore both tumor-initiating and -promoting chemicals. Induction of drug-metabolizing and antioxidant enzymes, including AhR-dependent CYP1A1, NQO-1 and AKR1C9, was detected in the rat liver epithelial WB-F344 "stem-like" cells. Additionally, WB-F344 cells express a functional, wild-type form of p53 protein, a biomarker of genotoxic events, and connexin 43, a basic structural unit of gap junctions forming an important type of intercellular communication. In this cellular model, two complementary assays have been established for detection of the modes of action associated with tumor promotion: inhibition of gap junctional intercellular communication (GJIC) and proliferative activity in confluent cells. We found that the PAHs and PCBs, which are AhR agonists, released WB-F344 cells from contact inhibition, increasing both DNA synthesis and cell numbers. Genotoxic effects of some PAHs that lead to apoptosis and cell cycle delay might interfere with the proliferative activity of PAHs. Contrary to that, the nongenotoxic low-molecular-weight PAHs and non-dioxin-like PCB congeners, abundant in the environment, did not significantly affect cell cycle and cell proliferation; however both groups of compounds inhibited GJIC in WB-F344 cells. The release from contact inhibiton by a mechanism that possibly involves the AhR activation, inhibition of GJIC and genotoxic events induced by environmental contaminants are three important modes of action that could play an important role in carcinogenic effects of toxic compounds. The relative potencies to inhibit GJIC, to induce AhR-mediated activity, and to release cells from contact inhibition were determined for a large series of PAHs and PCBs and their metabolites. In vitro bioassays based on detection of events on cellular level (deregulation of GJIC and/or proliferation) or determination of receptor-mediated activities in both ?$stem-like^{\circ}{\times}$ and hepatocyte-like liver cellular models are valuable tools for detection of modes of action of polyaromatic hydrocarbons. They may serve, together with concentration data, as a first step in their risk assessment.

• Molecules and Cells
• /
• v.45 no.3
• /
• pp.148-157
• /
• 2022

Hepatitis C virus (HCV) is a major cause of chronic liver disease and is highly dependent on cellular proteins for viral propagation. Using protein microarray analysis, we identified 90 cellular proteins as HCV nonstructural 5A (NS5A) interacting partners, and selected telomere length regulation protein (TEN1) for further study. TEN1 forms a heterotrimeric complex with CTC and STN1, which is essential for telomere protection and maintenance. Telomere length decreases in patients with active HCV, chronic liver disease, and hepatocellular carcinoma. However, the molecular mechanism of telomere length shortening in HCV-associated disease is largely unknown. In the present study, protein interactions between NS5A and TEN1 were confirmed by immunoprecipitation assays. Silencing of TEN1 reduced both viral RNA and protein expression levels of HCV, while ectopic expression of the siRNA-resistant TEN1 recovered the viral protein level, suggesting that TEN1 was specifically required for HCV propagation. Importantly, we found that TEN1 is re-localized from the nucleus to the cytoplasm in HCV-infected cells. These data suggest that HCV exploits TEN1 to promote viral propagation and that telomere protection is compromised in HCV-infected cells. Overall, our findings provide mechanistic insight into the telomere shortening in HCV-infected cells.