The Faculty of Medicine, University of the Ryukyus, started a "Public Health Project in Lao P.D.R.", which is one of the JICA projects, in 1992, and has been carrying out the "Sethathirath Hospital Improvement Project" since 1999 to improve medical treatment and health care in Lao P.D.R. Marked progress has been made. In addition, the projects of "Medical support for cleft lip and palate patients" performed by both the Oral and Maxillofacial Surgery Department of the University of the Ryukyus Hospital and Okinawa-Laos Cleft Lip and Palate Support Center have continued since 2001. So far, 231 cleft lip and palate patients have benefited from these projects, and favorable effects of medical education and technology transfer for medical staff in Laos have been obtained. Furthermore, during the 3-year period of another JICA project, called "From tooth brushing to oral health--Oral care education for Laos children", the dental caries rate of children in Donkoi Elementary School in Laos reduced from 92.5 to 61.8%, showing a decrease of 30.7%. Based on these encouraging results, in 2012, the JICA started a larger partnership project named Cha-ganzyu, which is from the dialect of Okinawa meaning health forever, focusing on oral health improvement of school children and local people of Laos.
Primitive reflexes can reappear with diseases of the brain, particularly those affecting the frontal lobes. Most studies on primitive reflexes have reported an association between such reflexes and brain damage, and the clinical symptoms of dementia. These reflexes can also be present during eating; however, their effects on eating function are difficult to evaluate. The purpose of the present study was to identify the frequency at which primitive reflexes reappear in elderly people, and to determine the effects that such reflexes have on eating function, nutritional status and prognosis.
To date, the major role of HPV16E6 in cancer has been considered to be its ability to inhibit the p53 tumor-suppressor protein, thereby thwarting p53-mediated cytotoxic responses to cellular stress signals. Here, we show that HPV16E6-dependent c-fos oncogenic protein expression contributes to AP-1 complex formation under oxidative stress in SiHa cells (HPV16-positive squamous cell carcinoma of the cervix). In addition, we examined the role of HPV16E6 in TGF-?-induced c-fos expression and found that the c-fos protein expression induced by TGF-? is HPV16E6 dependent. Thus, our results provide the first evidence that HPV16E6 contributes to AP-1 complex formation after both ligand-dependent and independent EGFR activation, suggesting a new therapeutic approach to the treatment of HPV-associated tumors.
Ethyl pyruvate, an aliphatic ester derived from pyruvate, reportedly has anti-inflammatory actions through inhibition of the transcription mediated by nuclear factor-kappa B (NF-?B). It was suggested that ethyl pyruvate inhibited NF-?B/DNA-binding activity through the covalent modification of RelA. However, the interaction of ethyl pyruvate with RelA in vitro has not been reported. In the present study, we confirmed that treatment of cultured alveolar epithelial cells, A549 cells, with tumor necrosis factor ? (TNF?) increased the NF-?B/DNA-binding activity. When the nuclear extract of the cells was incubated with ethyl pyruvate, the NF-?B/DNA-binding activity was strongly inhibited. Because we previously found that the NF-?B/DNA complex included RelA and p50, we bacterially expressed a deletion mutant of RelA, RelA (1-220), and a full-length form of p50. Incubation of RelA (1-220) or p50 with ethyl pyruvate induced dramatic changes in mobility in two types of nondenaturing gel electrophoresis. Electrophoretic mobility shift assays revealed that incubation of RelA (1-220) or p50 with ethyl pyruvate inhibited the DNA-binding activity. Furthermore, immunostaining of A549 cells revealed that ethyl pyruvate inhibited the nuclear association of RelA after TNF? treatment. These results suggest that ethyl pyruvate interacts with RelA and p50 to inhibit their functions at multiple points.
Caveolin-1 is implicated in the regulation of signal pathways. Adult T-cell leukemia (ATL) is a T-cell malignancy causatively associated with human T-cell leukemia virus type 1 (HTLV-1). To determine the role of caveolin-1 in leukemogenesis, we examined caveolin-1 expression levels in HTLV-1-infected T-cell lines and ATL cells. These cells expressed high levels of caveolin-1 compared with uninfected T-cell lines and normal peripheral blood mononuclear cells (PBMCs). Caveolin-1-positive ATL cells were detected in ATL lymph nodes and skin lesions, and caveolin-1 was also detected in the plasma of patients with ATL. Infection of a human T-cell line, an epithelial cell line, and normal PBMCs with HTLV-1 induced caveolin-1 expression. The viral protein Tax transcriptionally activated caveolin-1 gene through nuclear factor-kappaB and cAMP response element binding protein signal pathways. HTLV-1-infected T-cell lines, and ATL cells are known to be resistant to transforming growth factor beta (TGF-beta)-induced growth inhibition. Caveolin-1 was colocalized with TGF-beta type I receptor in HTLV-1-infected T-cell lines and suppressed TGF-beta signaling. Caveolin-1 knockdown in an HTLV-1-infected T-cell line exhibited susceptibility to TGF-beta. Thus, we describe a new function for Tax, repression of TGF-beta signaling through caveolin-1 expression, which may play a critical role in ATL leukemogenesis.
Inflammation is associated with disease progression and, by largely unknown mechanisms, has been said to drive oncogenesis. At inflamed sites, neutrophils deploy a potent antimicrobial arsenal that includes proteinases, antimicrobial peptides, and ROS. Reactive oxygen species (ROSs) induce chemokines. In the present study, the concentrations of IL-8 in culture supernatants of HeLa cells treated with ROS were determined by enzyme-linked immunosorbent assay. We used o-phenanthroline to deplete Fe(2+) in order to investigate the mechanisms through which ROSs induce IL-8 secretion in our system. The iron chelator o-phenanthroline effectively inhibited H(2)O(2)-induced ERK2 activation. Enzyme-linked immunosorbent assays showed that IL-8 protein secretion was elevated in ROS-treated HeLa cells. When Fe(2+) was removed from these cells, IL-8 secretion was inhibited. Collectively, these results indicate that Fe(2+)-mediated Erk pathway activation is an important signal transduction pathway in ROS-induced IL-8 secretion in epithelial cells.
For decades, platinum drugs have been the mainstay of cancer treatment. However, over time, drug resistance develops, leaving few treatment options. Here we show that platelet-derived growth factor ? receptor (PDGF ? receptor)-mediated signaling plays a key role in hepatocyte growth factor (HGF) receptor (c-Met) upregulation, which in turn is thought to play an important role in chemotherapy resistance. PDGF ? receptor inhibition eliminates cisplatin-dependent Met expression in cervical cancer cell lines. PDGF ? receptor inhibitors are widely used in clinical settings, suggesting that the clinical translation of our findings could reduce the suffering of people from drug resistance.
In the adult central nervous system (CNS), GABA and glycine (Gly) are predominant inhibitory neurotransmitters, negatively regulating glutamatergic transmission. In the immature CNS, on the other hand, they act as trophic factors, mediating morphogenesis. In the present study, to investigate their involvement in axonal regeneration, we morphologically examined changes in their signaling in mouse hypoglossal nuclei during degeneration and regeneration of hypoglossal nerves. We found that (1) expression and localization of presynaptic elements were not changed, (2) localization of gephyrin, which anchors GABA and Gly receptors, was spread on the surface of motor neuron cell bodies and dendrites, (3) KCC2-expression markedly decreased, (4) choline acetyltransferase, which mediates acetylcholine-synthesis, immediately disappeared from the motor neurons, and (5) the synaptic cleft of both excitatory and inhibitory synapses became irregularly wider, in the hypoglossal nuclei of the sutured side after the operation. These changes gradually normalized during regeneration. These results suggested that synthesis of acetylcholine may be stopped in the motor neuron after axotomy. GABA/Gly may be normally released from presynaptic terminals, be spilled over the original synaptic cleft, be diffused into the neighboring space, bind to extrasynaptically localized receptors, and mediate depolarization of the membrane potential of motor neurons during degeneration and regeneration. Furthermore, it was suggested that GABA/Gly signaling in postsynaptic motor neurons went back to being immature after axotomy, and may play an important role in axonal regeneration.
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