Purpose: Inhalation of air containing high amounts of particular matter (PM) causes various respiratory disorders including asthma, chronic obstructive pulmonary disease, and lung cancer. The changes of expression of inflammatory factors by polydeoxyribonucleotide (PDRN) administration in the PM10-exposed trachea inflammation model were evaluated. Methods: PM10 was administered to mouse trachea to induce acute inflammatory damage, and changes in inflammatory factors were observed after administration of PDRN and 3,7-dimethyl-1-propargylxanthine (DMPX) for 3 days daily. Expression of inflammatory cytokines, adenosine A2A receptor (A2AR), protein kinase A (PKA), 3΄,5΄-cyclic adenosine monophosphate responsive element binding protein (CREB) were detected by enzyme‐linked immunosorbent assay, immunofluorescence, and western blot assay. Results: PM-exposed trachea showed increased tumor necrosis factor (TNF)-α and interleukin (IL)-1β expression, and expression of TNF-α and IL-1β was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased nuclear factor (NF)-κB phosphorylation, and phosphorylation of nuclear factor-kappa B was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased expression of A2AR, but PDRN treatment more enhanced A2AR expression in PM-exposed mice. PKA phosphorylation was not changed and CREP phosphorylation was decreased, however PDRN treatment increased phosphorylation of PKA and CREB in PM-exposed mice. DMPX treatment blocked all the effects of PDRN on PM-exposed mice, demonstrating that the action of PDRN occurs via A2AR. Conclusions PDRN treatment attenuated inflammation in the trachea of the PM10-exposed mice. This improving effect of PDRN can be ascribed to the activation of A2AR through the cAMP-PKA pathway.

Purpose: This study aimed to investigate the effects of aroma foot baths on stress and sleep in terminally ill cancer patients. Methods: We performed a non-randomized interventioncontrol study with 30 terminal cancer patients who were admitted to a palliative care unit.Participants responded to questionnaires on stress and sleep before and after a 5-day interval. The intervention group received a daily aroma foot bath for 5 days. We performed multivariate regression analysis to examine the changes in outcomes on stress and sleep for the intervention group compared to the control group. Results: The differences in baseline characteristics between groups, excluding subjective economic status and general weakness, did not show statistical significance. In contrast to the control group, the intervention group showed a statistically significant change in physical stress and psychological stress levels, but significant changes were not observed in quality of sleep. Compared to the control group, the intervention group showed a significant reduction in physical stress (P=0.068) and psychological stress (P=0.021). Conclusion Aroma foot baths are effective for reducing stress in patients hospitalized with terminal cancer.

Purpose: Inhalation of air containing high amounts of particular matter (PM) causes various respiratory disorders including asthma, chronic obstructive pulmonary disease, and lung cancer. The changes of expression of inflammatory factors by polydeoxyribonucleotide (PDRN) administration in the PM10-exposed trachea inflammation model were evaluated. Methods: PM10 was administered to mouse trachea to induce acute inflammatory damage, and changes in inflammatory factors were observed after administration of PDRN and 3,7-dimethyl-1-propargylxanthine (DMPX) for 3 days daily. Expression of inflammatory cytokines, adenosine A2A receptor (A2AR), protein kinase A (PKA), 3΄,5΄-cyclic adenosine monophosphate responsive element binding protein (CREB) were detected by enzyme‐linked immunosorbent assay, immunofluorescence, and western blot assay. Results: PM-exposed trachea showed increased tumor necrosis factor (TNF)-α and interleukin (IL)-1β expression, and expression of TNF-α and IL-1β was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased nuclear factor (NF)-κB phosphorylation, and phosphorylation of nuclear factor-kappa B was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased expression of A2AR, but PDRN treatment more enhanced A2AR expression in PM-exposed mice. PKA phosphorylation was not changed and CREP phosphorylation was decreased, however PDRN treatment increased phosphorylation of PKA and CREB in PM-exposed mice. DMPX treatment blocked all the effects of PDRN on PM-exposed mice, demonstrating that the action of PDRN occurs via A2AR. Conclusions PDRN treatment attenuated inflammation in the trachea of the PM10-exposed mice. This improving effect of PDRN can be ascribed to the activation of A2AR through the cAMP-PKA pathway.

Purpose: This study aimed to investigate the effects of aroma foot baths on stress and sleep in terminally ill cancer patients. Methods: We performed a non-randomized interventioncontrol study with 30 terminal cancer patients who were admitted to a palliative care unit.Participants responded to questionnaires on stress and sleep before and after a 5-day interval. The intervention group received a daily aroma foot bath for 5 days. We performed multivariate regression analysis to examine the changes in outcomes on stress and sleep for the intervention group compared to the control group. Results: The differences in baseline characteristics between groups, excluding subjective economic status and general weakness, did not show statistical significance. In contrast to the control group, the intervention group showed a statistically significant change in physical stress and psychological stress levels, but significant changes were not observed in quality of sleep. Compared to the control group, the intervention group showed a significant reduction in physical stress (P=0.068) and psychological stress (P=0.021). Conclusion Aroma foot baths are effective for reducing stress in patients hospitalized with terminal cancer.

Many previous studies have shown reduced glucose uptake in the ischemic brain. In contrast, in a permanent unilateral common carotid artery occlusion (UCCAO) mouse model, our pilot experiments using 18F-fluorodeoxyglucose positron emission tomography (FDG PET) revealed that a subset of mice exhibited conspicuously high uptake of glucose in the ipsilateral hemisphere at 1 week post-occlusion (asymmetric group), whereas other mice showed symmetric uptake in both hemispheres (symmetric group). Thus, we aimed to understand the discrepancy between the two groups. Cerebral blood flow and histological/metabolic changes were analyzed using laser Doppler flowmetry and immunohistochemistry/Western blotting, respectively. Contrary to the increased glucose uptake observed in the ischemic cerebral hemisphere on FDG PET (p<0.001), cerebral blood flow tended to be lower in the asymmetric group than in the symmetric group (right to left ratio [%], 36.4±21.8 vs. 58.0±24.8, p=0.059). Neuronal death was observed only in the ischemic hemisphere of the asymmetric group. In contrast, astrocytes were more activated in the asymmetric group than in the symmetric group (p<0.05). Glucose transporter-1, and monocarboxylate transporter-1 were also upregulated in the asymmetric group, compared with the symmetric group (p<0.05, respectively). These results suggest that the increased FDG uptake was associated with relatively severe ischemia, and glucose transporter-1 upregulation and astrocyte activation. Glucose metabolism may thus be a compensatory mechanism in the moderately severe ischemic brain.

Purpose: Acute respiratory distress syndrome (ARDS) is characterized by its acute onset of symptoms such as bilateral pulmonary infiltrates, severe hypoxemia, and pulmonary edema. Many patients with ARDS survive in the acute phase, but then die from significant lung fibrosis. Methods: The effect of combination therapy with polydeoxyribonucleotide (PDRN) and pirfenidone on ARDS was investigated using human lung epithelial A549 cells. ARDS environment was induced by treatment with lipopolysaccharide and transforming growth factor (TGF)-β. Enzyme-linked immunoassay for connective tissue growth factor (CTGF) and hydroxyproline were conducted. Western blot for collagen type I, fibroblast growth factor (FGF), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 was performed. Results: In this study, 8-μg/mL PDRN enhanced cell viability. Combination therapy with PDRN and pirfenidone and pirfenidone monotherapy suppressed expressions of CTGF and hydroxyproline and inhibited expressions of collagen type I and FGF. Combination therapy with PDRN and pirfenidone and PDRN monotherapy suppressed expression of TNF-α and IL-1β. Conclusions The combination therapy with PDRN and pirfenidone exerted stronger therapeutic effect against lipopolysaccharide and TGF-β-induced ARDS environment compared to the PDRN monotherapy or pirfenidone monotherapy. The excellent therapeutic effect of combination therapy with PDRN and pirfenidone on ARDS was shown by promoting the rapid anti-inflammatory effect and inhibiting the fibrotic processes.

PURPOSE: The purpose of this study is to determine whether luminacin, a marine microbial extract from the Streptomyces species, has anti-tumor effects on head and neck squamous cell carcinoma (HNSCC) cell lines via autophagic cell death. MATERIALS AND METHODS: Inhibition of cell survival and increased cell death was measured using cell viability, colony forming, and apoptosis assays. Migration and invasion abilities of head and cancer cells were evaluated using wound healing, scattering, and invasion assays. Changes in the signal pathway related to autophagic cell death were investigated. Drug toxicity of luminacin was examined in in vitro HaCaT cells and an in vivo zebrafish model. RESULTS: Luminacin showed potent cytotoxicity in HNSCC cells in cell viability, colony forming, and fluorescence-activated cell sorting analysis. In vitro migration and invasion of HNSCC cells were attenuated by luminacin treatment. Combined with Beclin-1 and LC3B, Luminacin induced autophagic cell death in head and neck cancer cells. In addition, in a zebrafish model and human keratinocyte cell line used for toxicity testing, luminacin treatment with a cytotoxic concentration to HNSCC cells did not cause toxicity. CONCLUSION: Taken together, these results demonstrate that luminacin induces the inhibition of growth and cancer progression via autophagic cell death in HNSCC cell lines, indicating a possible alternative chemotherapeutic approach for treatment of HNSCC.
Apoptosis ; Autophagy* ; Carcinoma, Squamous Cell* ; Cell Death ; Cell Line ; Cell Survival ; Drug-Related Side Effects and Adverse Reactions ; Flow Cytometry ; Head and Neck Neoplasms ; Head* ; Humans ; Keratinocytes ; Neck* ; Signal Transduction ; Streptomyces ; Toxicity Tests ; Wound Healing ; Zebrafish

PURPOSE: Tolfenamic acid (TA), a non-steroidal anti-inflammatory drug, is known to exhibit antitumor effects in various cancers apart from nasopharyngeal cancer (NPC). NPC exhibits high invasiveness, as well as metastatic potential, and patients continue to suffer from residual, recurrent, or metastatic disease even after chemoradiation therapy. Therefore, new treatment strategies are needed for NPC. In this study, we investigated the efficacy and molecular mechanisms of TA in NPC treatment. MATERIALS AND METHODS: TA-induced cell death was detected by cell viability assay in the NPC cell lines, HNE1 and HONE1. Wound healing assay, invasion assay, and Western blot analysis were used to evaluate the antitumor effects of TA in NPC cell lines. RESULTS: Treatment with TA suppressed the migration and invasion of HNE1 and HONE1 cells. Hepatocyte growth factor enhanced the proliferation, migration, and invasion abilities of NPC cells. This enhancement was successfully inhibited by TA treatment. Treatment with TA increased phosphorylation of p38, and the inhibition of p38 with SB203580 reversed the cytotoxic, anti-invasive, and anti-migratory effects of TA treatment in NPC cell lines. Moreover, inhibition of p38 also reversed the decrease in expression of Slug that was induced by TA treatment. CONCLUSION: In conclusion, the activation of p38 plays a role in mediating TA-induced cytotoxicity and inhibition of invasion and migration via down-regulation of Slug.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*pharmacology/therapeutic use ; Cell Line, Tumor ; Cell Movement/*drug effects ; Cell Proliferation/*drug effects ; Cell Survival/*drug effects ; Down-Regulation ; Gastropoda ; Gene Expression Regulation, Neoplastic/drug effects ; Hepatocyte Growth Factor/metabolism/*pharmacology ; Humans ; Imidazoles ; MAP Kinase Signaling System/drug effects ; Nasopharyngeal Neoplasms/*drug therapy/metabolism/pathology ; Neoplasm Invasiveness/*prevention & control ; Phosphorylation/drug effects ; Pyridines ; ortho-Aminobenzoates/*pharmacology/therapeutic use

PURPOSE: The purpose of this study is to determine the relationship between the repetitive flexion or extension posture on the cervical spine on labor and degenerative change of the cervical spine, and the factors affecting degenerative change of the cervical spine. MATERIALS AND METHODS: To determine the factors affecting degenerative change of the cervical spine, age, sex, height, weight, body mass index, smoking, diabetes mellitus (DM), time engaging in labor, and cervical spine posture (flexion or extension) required repetitively on labor were investigated in the subjects. In addition, to evaluate the level of degenerative change of the cervical spine on 83 people in the flexion group (flexion strain) and 83 people in the extension group (extension strain), cervical degenerative index (CDI) in the simple cervical spine lateral radiograph was used to score (0-60 points) the degenerative severity. RESULTS: A total of 166 subjects (flexion group: 83 people, extension group: 83 people) participated in this study, and for the CDI, the cervical spine flexion group scored 7.8±6.2 points, and the cervical spine extension group scored 12.2±6.0 points to show that the cervical spine extension group had significant degenerative change in the cervical spine. In the multiple linear regression test performed to verify the risk factors affecting the degenerative change of the cervical spine, age (p=0.004), contraction of DM (p=0.029), and extension posture of cervical spine (p<0.001) influenced the degenerative change of the cervical spine. CONCLUSION: Repetitive extension posture on the cervical spine on labor and contraction of diabetes affected degenerative change of the cervical spine, therefore, training in medical care and posture on labor are required to prevent the progression of degenerative change in the cervical spine.
Agriculture* ; Body Weight ; Cervical Vertebrae ; Diabetes Mellitus ; Female ; Linear Models ; Neck* ; Posture ; Risk Factors* ; Smoke ; Smoking ; Spine ; Spondylosis*

PURPOSE: Past studies have reported that S-allylcysteine (SAC) inhibits the migration and invasion of cancer cells through the restoration of E-cadherin, the reduction of matrix metalloproteinase (MMP) and Slug protein expression, and inhibition of the production of reactive oxygen species (ROS). Furthermore, evidence is emerging that shows that ROS induced by radiation could increase Met activation. Following on these reports of SAC and Met, we investigated whether SAC could suppress Met activation. MATERIALS AND METHODS: Wound healing, invasion, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT), soft agar colony forming, western blotting, and gelatin zymography assays were performed in the human nasopharyngeal cancer cell lines HNE1 and HONE1 treated with SAC (0, 10, 20, or 40 mM) and hepatocyte growth factor (HGF). RESULTS: This study showed that SAC could suppress the migration and invasion of HNE1 and HONE1 cell lines by inhibiting p-Met. An increase of migration and invasion induced by HGF and its decrease in a dose dependent manner by SAC in wound healing and invasion assays was observed. The reduction of p-Met by SAC was positively correlated with p-focal adhesion kinase (p-FAK) and p-extracellular related kinase (p-ERK in both cell lines). SAC reduced Slug, MMP2, and MMP9 involved in migration and invasion with the inhibition of Met-FAK signaling. CONCLUSION: These results suggest that SAC inhibited not only Met activation but also the downstream FAK, Slug, and MMP expression. Finally, SAC may be a potent anticancer compound for nasopharyngeal cancer treated with radiotherapy.
Agar ; Blotting, Western ; Cadherins ; Cell Line ; Emigration and Immigration ; Gastropoda ; Gelatin ; Hepatocyte Growth Factor* ; Hepatocytes* ; Humans ; Nasopharyngeal Neoplasms* ; Phosphotransferases ; Radiotherapy ; Reactive Oxygen Species ; Wound Healing