Cordycepin, a derivative of the nucleoside adenosine, is one of the active components extracted from fungi of genus Cordyceps, and has been shown to have many pharmacological activities. In this study, we investigated the effects of cordycepin on proliferation and apoptosis of human gastric cancer AGS cells, and its possible mechanism of action. Treatment of cordycepin resulted in significant decrease in cell viability of AGS cells in a concentration-dependent manner. A concentration-dependent apoptotic cell death was also measured by agarose gel electrophoresis and flow cytometery analysis. Molecular mechanistic studies of apoptosis unraveled cordycepin treatment resulted in an enhanced expression of tumor necrosis factor-related apoptosis-inducing ligand, death receptor 5 and Fas ligand. Furthermore, up-regulation of pro-apoptotic Bax, and down-regulation of anti-apoptotic Bcl-2 and Bcl-xL expression were also observed in cordycepin-treated AGS cells. These were followed by activation of caspases (caspase-9, -8 and -3), subsequently leading to poly (ADP-ribose) polymerase cleavage. Taken together, these findings indicate that cordycepin induces apoptosis in AGS cells through regulation of multiple apoptotic pathways, including death receptor and mitochondria. Although further mechanical studies are needed, our results revealed that cordycepin can be regarded as a new effective and chemopreventive compound for human gastric cancer treatment.
Receptor-interacting protein kinase 1 (RIPK1) and RIPK3 are members of the serine or threonine protein kinase superfamily that phosphorylates the hydroxyl group of serine or threonine through the highly conserved kinase region. The RIPK family plays a crucial role not only in inflammation and innate immunity, but also in mediating programmed cell death, such as apoptosis and necroptosis. The interaction between RIPK1 and other TNFR1-related proteins has been shown to assemble a signaling complex I that controls activation of the pro-survival transcription factor NF-κB upon binding of cytokines to TNF receptor 1 (TNFR1). Moreover, RIPK1 and RIPK3 interact through their RIP homotypic interaction motifs (RHIMs) to mediate programmed necrosis, which has long been considered an accidental and uncontrolled cell death form with morphological characteristics differing from those of apoptosis. Highly conserved sequences of RHIM in RIPK1 and RIPK3 were shown to regulate their binary interaction, leading to assembly of a cytosolic amyloid complex termed the “necrosome”. The necrosome also contains mixed lineage kinase domain-like protein (MLKL), which has been found recently to be a substrate of RIPK3 to mediate downstream signaling. This review provides an overview of the functional and physiological characteristics of RIPKs and MLKL in TNF signaling.
The health benefits of garlic (Allium sativum L.) are derived from a wide variety of components and from the different ways it is administered. The known health benefits of garlic include cardiovascular protective effects, stimulation of immune function, reduction of blood glucose level, protection against microbial, viral and fungal infections, as well as anticancer effects. In the present study, it was examined the effects of water extract of A. sativum (WEAS) on the growth of cultured human tumor cells in order to investigate its anti-proliferative mechanism. Treatment of WEAS to tumor cells resulted in the growth inhibition, especially in leukemia cells, which was associated with induction of G2/M arrest of the cell cycle and apoptosis. In order to further explore the critical events leading to apoptosis in WEAS-treated U937 human leukemia cells, the following effects of WEAS on components of the mitochondrial apoptotic pathway were examined: generation of reactive oxygen species (ROS), alteration of the mitochondrial membrane potential (MMP), and the expression changes of Bcl-2 and IAP family proteins. The cytotoxic effect of WEAS was mediated by its induction of apoptosis as characterized by the occurrence of DNA ladders, apoptotic bodies and chromosome condensation in U937 cells. The WEAS-induced apoptosis in U937 cells was correlated with the generation of intracellular ROS, collapse of MMP, activation of caspase-3 and down-regulation of anti-apoptotic proteins. The quenching of ROS generation with antioxidant N-acetyl-L-cysteine conferred significant protection against WEAS-elicited ROS generation, caspase-3 activation, G2/M arrest and apoptosis. In conclusion, the present study reveals that the cellular ROS generation plays a pivotal role in the initiation of WEAS-triggered apoptotic death in U937 cells.
While there were separation, confrontation and conflicts in Yungnam confucian group in seventeenth century, Nampa Jang Hak(1614~1669), was one of the representative figure among Yeoheon's pupils in doing the project of Yeoheon's enshrinement and strengthening the solidarity of Yeoheon's students. His family had close relationship with Yeoheon, and he started to receive instructions from Yeoheon in his early ages. Owing to the close relationship with Yeoheon, Nam pa did the leading role in the memorial projects, such as publishing the collection of works, and enshrining Yeoheon's tablet in Seowon, a private academy. Especially, he defined Yeoheon's scholarstic mantle as 'assertion that does not come from the teacher whom specifies(不由師承論)' and tried to link Yeoheon's work with other confucian saints' works. This linkage functioned as a stepstone for the projects of enshrining Yeoheon in the memorial hall of their private school, Seowon. Accordingly, in this paper, Nampa's life and academic activities are investigated, considering he was in the middle of the turmoil of separation and conflict of Yeongnam confucian group. Specifically, Nampa was most actively involved in the project of enshrining Yeoheon, and he defined Yeoheon's scholaristic mantle as 'assertion that does not come from the teacher whom specifies(不由師承論)'. Basing on this understanding, he pushed ahead the controversial project of enshrining Yeoheon's tablet in Imgo Seowon(臨皐書院). Although Nampa's scholaric key concepts cannot be found clearly, he tried to diffuse Yeoheon's academic thought over other regions, and by this activity, he tried to solidify Yeoheon's scholarstic achievement and status. His activity confirms that he was most distinctive student of Yeoheon. Ultimately, He was the central figure of late times of Yeoheon school, comparing to the most prestigious fifteen scholars(樑頌十五賢) and ten scholars(旅門十哲) who represented the early times of Yeoheon school.
The Hoeamsa Temple of Yangju City was established at least during the late Korea Dynasty. This temple was rebuilt several times with the support of the royal family from the late Korea Dynasty to the early Joseon Dynasty. It was continually rebuilt in association with JiGong monk, HyeKeun monk, and MuHak monk. Hoeamsa temple was leading the Buddhist culture as a Buddhist center of the Joseon Dynasty . It was destroyed in the late Joseon Period. This site has been excavated several times since 1997. Various roofing tiles were unearthed. Of these tiles the edge of eaves are the artifacts showing the best features of this era. In this temple site has been excavated a variety of Sanskrit roof tiles. These tiles were made using superior technique. On the roof tiles are engraved Sanskrit mantras with a variety of 1 to 9 words. The jeongbeopkkye mantra(oṃ raṃ) and six-word mantra(oṃ ma ṇi pa dme hūṃ) were discovered the most. These mantras were believe to expel several evils from the Buddhist temple. It must have been that the six-word mantra culture became prevalent and provided a turning point in the history of Korean Buddhism. We can clearly know when some of the Sanskrit roof tiles were first manufactured. These roof tiles are the absolute standard of the other Sanskrit roof tiles excavated from different Buddhist temples. The master craftsmen must have been very skilled, understood the mantra very well, and had deep faith in the Sanskrit mantra. Hoeamsa Temple is a milestone in studying the Sanskrit roof tiles. More studies on various aspects are expected to be followed.
The purpose of this study is to investigate whether character education program using Youtube PSAs affect psychological and social maturity of pre-service teachers. For data collections, questionnaires and semi-structured interview are used by 23 sophomores majoring in teacher education. The results are as follows. First, the participants showed highly significant improvement on each of two maturities as well as entire psychological and social maturity. Second, the score of factors of social maturity was lower than that of those of psycho maturity. it could be estimated that college students live in nuclear family and individualization is valued more. Third, while pre-test scores of entire psycho-social maturity are not statistically significant, post-test scores of each of psycho-social maturity indicated statistical significance. In particular, unlike pre-test, there is a strong positive correlation in post-test due to mutually positive impact of two factors. Fourth, there was no statistically significant sex difference. Lastly, according to the result of interview, participants had strong views on the effects of personality education associated with use of Youtube PSAs on motivation and focus in class, caring for others, and leading to positive behaviors.
In this paper, I found the leadership core-value of the Sunbai(선배) a man of refined taste. I studied twelve Sunbai considered as a man of refined taste in this research. I focused on the aspect showing common worth among their various abilities and cultural contributions, a point of view of classifying them into one form called Sunbai a man of refined taste. As the core value is the basis of supporting the individual identity, so the leadership core-value is the source and philosophical base of displaying the leadership. Our Sunbai combining character and knowledge show common structure in their personal growth and showing the leadership. It is that they embodied the stage of cultivating themselves(修身, Self), considering the relation with others(齊家, Relation), leading the organization(治國, Team), and making efforts for and having influence on the community(平天下, Community) throughout their own life. I examined how to display the leadership in the four fields on a case by case basis and then constructed the leadership model of the Sunbai a man of refined taste by synthesizing them. As a result, I considered their leadership core-value as the intercommunication and named it 'Leadership of Muaesabang(無碍四方)'. Also, I confirmed that it is still very valuable in these days of aiming at the open society and the harmony of the diverse civilization.
Given that music is not part of the national/regular curriculum and how music therapy is a new endeavor in the United Arab Emirates (UAE), this study aimed to investigate parents' perceptions of the music therapy given to their children with disabilities in the UAE. A survey was administered to 33 parents of children with disabilities living in Sharjah, UAE. The survey consisted of 43 questions related to characteristics of the music therapy sessions that the participants' children received and the parents' satisfaction with their children's music therapy. The results showed that participants reported a high level of satisfaction with the music therapy provided to their children. In terms of their participation in music therapy sessions, 33.3% of parents co-participated in music therapy sessions with their children, and 45.5% of parents observed their children's sessions. Parents who had direct participation in music therapy sessions were significantly more satisfied with their children's music therapy (p < .05) and perceived greater positive changes in their children as a result of the therapy (p < .05). Parents perceived their children as being able to positively respond to music, leading to positive changes in behavior. Despite these benefits, participants also reported the need for formal opportunities for family members to learn about the applications and outcomes of music therapy. The findings of this study supports the implementation of music therapy throughout the UAE and point to the need for future studies as music therapy expands across the country.
Background: Incretin impairment, characterized by insufficient secretion of L-cell-derived glucagon-like peptide-1 (GLP-1), is a defining step of type 2 diabetes mellitus (T2DM). Ginsenoside compound K (CK) can stimulate GLP-1 secretion; however, the potential mechanism underlying this effect has not been established. Methods: CK (40 mg/kg) was administered orally to male db/db mice for 4 weeks. The body weight, oral glucose tolerance, GLP-1 secretion, gut microbiota sequencing, bile acid (BA) profiles, and BA synthesis markers of each subject were then analyzed. Moreover, TGR5 expression was evaluated by immunoblotting and immunofluorescence, and L-cell lineage markers involved in L-cell abundance were analyzed. Results: CK ameliorated obesity and impaired glucose tolerance in db/db mice by altering the gut microbiota, especially Ruminococcaceae family, and this changed microbe was positively correlated with secondary BA synthesis. Additionally, CK treatment resulted in the up-regulation of CYP7B1 and CYP27A1 and the down-regulation of CYP8B1, thereby shifting BA biosynthesis from the classical pathway to the alternative pathway. CK altered the BA pool by mainly increasing LCA and DCA. Furthermore, CK induced L-cell number expansion leading to enhanced GLP-1 release through TGR5 activation. These increases were supported by the upregulation of genes governing GLP-1 secretion and L-cell differentiation. Conclusions: The results indicate that CK improves glucose homeostasis by increasing L-cell numbers, which enhances GLP-1 release through a mechanism partially mediated by the gut microbiota-BA-TGR5 pathway. Therefore, that therapeutic attempts with CK might be useful for patients with T2DM.
The prolyl 3-hydroxylase family member 4 (P3H4), is associated with post-translational modification of fibrillar collagens and aberrantly activated in cancer leading to tumor progression. However, its role in clear cell renal cell carcinoma (ccRCC) is still unknown. Here we reported that P3H4 was highly expressed in renal cancer tissues and significantly positive correlated with poor prognosis. Knockdown of P3H4 inhibited the proliferation, migration and metastasis of renal cancer cells in vitro and in vivo, and also, overexpression of it enhanced the oncogenic process. Mechanistically, P3H4 depletion decreased the levels of GDF15-MMP9 axis and repressed its downstream signaling. Further functional studies revealed that inhibition of GDF15 suppressed renal cancer cell growth and GDF15 recombinant human protein (rhGDF15) supplementation effectively rescued the inhibitory effect induced by P3H4 knockdown. Moreover, decreased levels of MMP9 caused by inhibition of P3H4-GDF15 signaling constrained the expression of PD-L1 and suppression of P3H4 accordingly promoted anti-tumor immunity via stimulating the infiltration of CD4+ and CD8+ T cells in syngeneic mice model. Taken together, our findings firstly demonstrated that P3H4 promotes ccRCC progression by activating GDF15-MMP9-PD-L1 axis and targeting P3H4-GDF15-MMP9 signaling pathway can be a novel strategy of controlling ccRCC malignancy.
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