Constant and intermittent hypoxia modulates immunity, oxidative status, and blood components of red seabream and increases its susceptibility to the acute toxicity of red tide dinoflagellate.

Hypoxia is an increasing threat to aquatic ecosystems and its impact on economically and ecologically important marine fish species needs to be studied. Especially, the consequences of hypoxia when occurring along with harmful algal blooms (HABs) are currently not well documented. In this study, we investigated the effect of constant and intermittent (daily and weekly) hypoxia on respiration, immunity, hematological parameters, and oxidative status of red seabream for 2, 4, and 6 weeks. Under constant and daily intermittent hypoxia, respiration rate significantly increased in 2 weeks compared to the control. Constant and daily intermittent hypoxia caused significant decreases in the activity of alternative complement pathway, lysozyme, and the level of total immunoglobulin (Ig), as well as significant increases in the concentrations of cortisol, hemoglobin, red blood cells, and white blood cells. A significantly higher level of malondialdehyde was measured for all hypoxia-exposed groups, indicating lipid peroxidation and oxidative stress. At 4 and 6 week, the level of glutathione and enzymatic activities of glutathione reductase and glutathione peroxidase were significantly decreased after constant and daily intermittent hypoxia challenge. The enzymatic activities of superoxide dismutase and catalase were significantly increased at 2 and 4 weeks, but they were decreased after 6 weeks by constant and daily intermittent hypoxia. Constant and daily intermittent hypoxia with subsequent non-toxin producing dinoflagellate Cochlodinium polykrikoides treatment significantly reduced the respiration rate in 3 and 24 h exposure and survival rate of red seabream. Taken together, the red seabream can be vulnerable to HABs under hypoxia condition through inhibition of immunity and antioxidant defense ability. Our findings are helpful in better understanding of molecular and physiological effects of hypoxia, which can be used in aquaculture and fisheries management.

FBXO11 represses cellular response to hypoxia by destabilizing hypoxia-inducible factor-1α mRNA.

The transcriptional factor hypoxia-inducible factor-1α (HIF-1α) is induced under hypoxia and plays crucial roles in cancer progression and angiogenesis. Protein arginine methyltransferases (PRMTs), 11 isoforms of which have been identified so far, modulates the functions of diverse proteins by catalyzing arginine methylation in post-translational level. PRMT9 (alternatively named FBXO11) and PRMT11 (FBXO10) are expected to have the E3 ubiquitin ligase activity through their F-box domains as well as the methyltrasferase activity. Given previous studies examining roles of 8 PRMT isoforms (PRMT1-8) in the HIF-1 signaling pathway, PRMT1 and PRMT5 were demonstrated to regulate HIF-1α expression in opposite ways. We herein examined if FBXO10 and FBXO11 participate in the HIF-1 signaling pathway. Consequently, the siRNA-mediated knockdown of FBXO11 facilitated HIF-1α expression in various cancer cells and HIF-1-driven gene expressions, but the FBXO10 knockdown did not. Mechanistically, FBXO11 was found to inhibit de novo synthesis of HIF-1α protein by destabilizing HIF-1α mRNA. Since a FBXO11 mutant lacking F-box failed to reverse the HIF-1α expression by FBXO11 knockdown, the FBXO11 regulation of HIF-1α may be attributed to the ubiquitination of some proteins controlling HIF-1α mRNA stability. Considering the oncogenic roles of HIF-1α, FBXO11 is suggested to act as a tumor suppressor and also to be a potential target for cancer therapy.

Deferoxamine Improves Alveolar and Pulmonary Vascular Development by Upregulating Hypoxia-inducible Factor-1α in a Rat Model of Bronchopulmonary Dysplasia.

Fetal lung development normally occurs in a hypoxic environment. Hypoxia-inducible factor (HIF)-1α is robustly induced under hypoxia and transactivates many genes that are essential for fetal development. Most preterm infants are prematurely exposed to hyperoxia, which can halt hypoxia-driven lung maturation. We were to investigate whether the HIF-1α inducer, deferoxamine (DFX) can improve alveolarization in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was produced by intra-amniotic lipopolysaccharide (LPS) administration and postnatal hyperoxia (85% for 7 days), and DFX (150 mg/kg/d) or vehicle was administered to rat pups intraperitoneally for 14 days. On day 14, the rat pups were sacrificed and their lungs were removed and examined. A parallel in vitro study was performed with a human small airway epithelial cell line to test whether DFX induces the expression of HIF-1α and its target genes. Alveolarization and pulmonary vascular development were impaired in rats with BPD. However, DFX significantly ameliorated these effects. Immunohistochemical analysis showed that HIF-1α was significantly upregulated in the lungs of BPD rats treated with DFX. DFX was also found to induce HIF-1α in human small airway epithelial cells and to promote the expression of HIF-1α target genes. Our data suggest that DFX induces and activates HIF-1α, thereby improving alveolarization and vascular distribution in the lungs of rats with BPD.

Sildenafil alleviates bronchopulmonary dysplasia in neonatal rats by activating the hypoxia-inducible factor signaling pathway.

Bronchopulmonary dysplasia (BPD) is a major cause of morbidity in premature infants receiving oxygen therapy. Currently, sildenafil is being examined clinically to improve pulmonary function in patients with BPD. Based on the pharmacological action of sildenafil, the elevation of cyclic guanosine 3',5'-monophosphate (cGMP) in lung tissue is considered to underlie its beneficial effects, but this mechanism is not understood at the molecular level. Here, we examined the possibility that sildenafil helps the pulmonary system adapt to hyperoxic stress. To induce BPD, fetal rats were exposed to LPS before delivery, and neonates were exposed to hyperoxia, followed by intraperitoneal injections of sildenafil. Alveolarization was impaired in rats exposed to hyperoxia, and alveolarization significantly recovered with sildenafil. An immunohistochemical examination revealed that sildenafil effectively increased vascular distribution in lung tissue. Furthermore, the oxygen sensor hypoxia-inducible factor (HIF)-1/2α and the angiogenic factor vascular endothelial growth factor (VEGF) were highly expressed in the lungs of sildenafil-treated rats. In human small-airway epithelial cells, HIF-1/2α and its downstream genes, including VEGF, were confirmed to be induced by sildenafil at both the protein and mRNA levels. Mechanistically, cGMP in airway cells accumulated after sildenafil treatment because of interfering phosphodiesterase Type 5, and subsequently cGMP activated HIF-mediated hypoxic signaling by stimulating the phosphoinositide 3-kinase (PI3K)-v-akt murine thymoma viral oncogene homolog 1 (AKT)-mammalian target of rapamycin (mTOR) pathway. This study provides a better understanding about the mode of action for sildenafil, and suggests that HIF can be a potential target for treating patients with BPD.

Complete mitochondrial genome of the crinoid Poliometra prolixa (Crinoidea: Comatulida: Antedonidae).

Poliometra prolixa Sladen, 1881, is a comatulid crinoid found in the Arctic deep sea. In this study, we report the complete mitochondrial genome sequence of P. prolixa (Comatulida: Antedonidae). The complete mitogenome of P. prolixa was 15,916 bp long and comprised 13 protein-coding genes (PCGs), 22 transfer RNA genes, and 2 ribosomal RNA genes. The base composition of the P. prolixa mitogenome was 24.0% A, 44.9% T, 19.0% G, and 12.1% C. Phylogenetic analysis using all PCGs of the complete mitogenome confirmed the inclusion of P. prolixa within the Comatulida.

Chronic exposure to environmental concentrations of harmful algal bloom-forming dinoflagellates induces oxidative stress and reduces immune and hepatic functions in red seabream.

Harmful algal blooms (HABs) caused by dinoflagellates can be detrimental to aquaculture and fisheries. However, little is known regarding their ichthyotoxic effects on fish, particularly after chronic exposure to sublethal levels. In this study, significant modulations in physiology, immunity, antioxidant components, and hepatic indicators owing to non-toxin-producing dinoflagellate strains (Alexandrium affine and Cochlodinium polykrikoides) were analyzed in juvenile red seabream, Pagrus major, exposed to sublethal concentrations (0, 1, and 100 cells mL-1) for 60 days. At 60 days, higher mortality was induced by A. affine than by C. polykrikoides. Significant increases in respiration rate and plasma cortisol were observed in red seabream exposed to 100 cells mL-1 of the two dinoflagellates. Intracellular reactive oxygen species and malondialdehyde levels were significantly elevated in the gill and liver tissues in response to 100 cells mL-1 of either dinoflagellate. Immunity parameters such as alternative complement activity, lysozyme activity, and total immunoglobulin content were significantly decreased during exposure to 100 cells mL-1 of the two dinoflagellates. Although no significant change was observed in the gonadosomatic index, the hepatosomatic index was significantly decreased by exposure to 100 cells mL-1 of the two dinoflagellates on day 60. The significant decrease in enzymatic activities of ethoxyresorufin-O-deethylase, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase upon exposure to 100 cells mL-1 of either dinoflagellate suggested impaired hepatic function through prolonged exposure. Our results suggest that consistent exposure to sublethal concentrations of HAB-forming dinoflagellates is detrimental to fish physiology and biochemical defenses.

Hypoxia-inducible factor α subunit stabilization by NEDD8 conjugation is reactive oxygen species-dependent.

Hypoxia-inducible factor α proteins (HIF-αs) are regulated oxygen dependently and transactivate numerous genes essential for cellular adaptation to hypoxia. NEDD8, a member of the ubiquitin-like family, covalently binds to its substrate proteins, and thus, regulates their stabilities and functions. In the present study, we examined the possibility that the HIF signaling is regulated by the neddylation. HIF-1α expression and activity were inhibited by knocking down APPBP1 E1 enzyme for NEDD8 conjugation but enhanced by ectopically expressing NEDD8. HIF-1α and HIF-2α were identified to be covalently modified by NEDD8. NEDD8 stabilized HIF-1α even in normoxia and further increased its level in hypoxia, which also occurred in von Hippel-Lindau (VHL) protein- or p53-null cell lines. The HIF-1α-stabilizing effect of NEDD8 was diminished by antioxidants and mitochondrial respiratory chain blockers. This suggests that the NEDD8 effect is concerned with reactive oxygen species driven from mitochondria rather than with the prolyl hydroxylase (PHD)/VHL-dependent oxygen-sensing system. Based on these findings, we propose that NEDD8 is an ancillary player to regulate the stability of HIF-1α. Furthermore, given the positive role played by HIF-αs in cancer promotion, the NEDD8 conjugation process could be a potential target for cancer therapy.

Characterization and phylogenetic analysis of the complete mitochondrial genome of the rainbow krib, Pelvicachromis pulcher (Perciformes: Cichlidae).

We report the complete mitochondrial genome information of the rainbow krib, Pelvicachromis pulcher (Boulenger 1901). Illumina HiSeq genome sequencing allowed the assembly of a circular mitogenome of 17,196 base pairs (bp) from P. pulcher consisting of 47% GC nucleotides, 13 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a putative control region in the typical teleost gene composition. The gene order of the P. pulcher mitogenome was identical to that of other cichlid species. A maximum likelihood phylogenetic tree based on mitochondrial PCGs showed a relationship of P. pulcher with a cichlid Tylochromis polylepis (Boulenger 1900), suggesting that more complete mitogenomes are needed to explore mitogenome evolution in West African tribes and riverine cichlids, as this genomic information is the first complete mitogenome in the tribe Chromidotilapiini.

Complete mitochondrial genome of the six-line wrasse Pseudocheilinus hexataenia (Labriformes, Labridae).

Here, we report the complete mitogenome information of the six-line wrasse Pseudocheilinus hexataenia (Bleeker, 1857). Genome sequencing using the Illumina HiSeq platform allowed the assembly of a circular mitochondrial genome of 17,111 bp from P. hexataenia, consisting of 54% AT nucleotides, 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a putative control region in the typical Labriformes gene composition. The gene order of the P. hexataenia mitochondrion was identical to that of the Labridae mitogenomes. Phylogenetic reconstruction places P. hexataenia with a close relationship with the mitogenome of the goldsinny wrasse, Ctenolabrus rupestris.

Chronic exposure to sublethal concentrations of saxitoxin reduces antioxidant activity and immunity in zebrafish but does not affect reproductive parameters.

Saxitoxin produced by dinoflagellates and cyanobacteria can be transferred to humans through intoxicated organisms such as fish, but limited research has addressed the adverse effects of this toxin on aquatic organisms. In this study, we measured the potential effects of a 90-day exposure to saxitoxin (0.1 or 1 µg·L - 1) on body weight and length, antioxidant defense system, immunity, sex hormones, and genes involved in associated key metabolic pathways in zebrafish (Danio rerio). Significant impairments in body weight and length were observed in response to 1 µg·L - 1 saxitoxin in both male and female zebrafish. A significant increase in the levels of malondialdehyde, together with decreased enzymatic activities of catalase and superoxide dismutase, was observed in fish of both sexes exposed to 1 µg·L - 1 saxitoxin, indicating the occurrence of lipid peroxidation and oxidative stress. Immune parameters such as alternative complement activity, lysozyme activity, and immunoglobulin content were also significantly reduced. However, exposure of male and female zebrafish to saxitoxin for 90 days did not significantly affect reproductive parameters such as the gonadosomatic index and plasma concentrations of vitellogenin, estradiol, and 11-keto testosterone. Transcriptional responses showed similar trends to those of the biochemical parameters, as genes involved in the antioxidant defense system and immunity were downregulated, whereas the transcription of genes related to reproductive metabolism showed no significant change upon treatment with 1 µg·L - 1 saxitoxin. Our findings indicate that long-term exposure to a sublethal concentration of saxitoxin can inhibit growth through induction of oxidative stress and immunosuppression, while the reproductive parameters of zebrafish are not a main target of this toxin at sublethal concentrations.

The complete mitochondrial genome of Lamprologus signatus (Perciformes: Cichlidae).

In this study, the complete 16,583 bp mitochondrial genome of Lamprologus signatus (Poll, 1952) was determined from a specimen sourced from Lake Tanganyika. The mitogenome contains 37 genes [13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, and 22 transfer RNA (tRNA) genes] and a putative control region, which consists of 27.1% A, 27.0% T, 29.9% C, and 16.0% G, with a total G + C content of 45.9%. A maximum likelihood phylogenetic tree based on mitochondrial PCGs suggested that L. signatus is clustered with members of the tribes Haplochromini and Tropheini. As this is the first report of the entire mitogenome in the tribe Lamprologini, the complete mitochondrial sequence information of L. sigantus will be useful in determining phylogenetic relationships of Pseudocrenilabrinae tribes.

The complete mitochondrial genome of the terebellid polychaete Thelepus plagiostoma (Terebellida; Terebellidae).

Here, we report the complete mitogenome information of the terebellid polychaete, Thelepus plagiostoma (Schmarda, 1861). Genome sequencing by Illumina HiSeq platform permitted assembly of a circular mitochondrial genome of 15,628 bp from T. plagiostoma consisting of 67% AT nucleotides, 13 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a non-coding region in the typical annelid gene composition. Gene order of the T. plagiostoma mitochondrion is identical to those of the Terebelliformia mitogenomes. Phylogenetic reconstruction places T. plagiostoma within the monophyletic subclass Sedentaria, a sister to Pista cristata in the suborder Terebelliformia.

Complete mitochondrial genome of the marine polychaete Hediste japonica (Phyllodocida, Nereididae).

To date, only five species are registered in the genus Hediste, and complete mitochondrial genome is reported in one species, Hediste diadroma. In this study, a complete 15,783 bp genome for the marine polychaete H. japonica mitochondrion was assembled through Illumina HiSeq platform. The complete mitochondrial genome of H. japonica contained 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and one control region. Overall genomic structure and gene orientation of H. japonica mitogenome are identical to those of H. diadroma. Phylogenetic analysis using the maximum likelihood method validated the sister relationship between Hediste sp. and other polychaetes. This information will be useful to understand geographical distribution, phylogenetic relationship, and evolutionary history of marine polychates.

Complete mitochondrial genome of the crinoid echinoderm, Florometra species (Echinodermata, Crinoidea).

In this study, we report the sequence of the mitochondrial genome (mitogenome) of the crinoid echinoderm, Florometra species (Echinodermata, Crinoidea). The complete mitogenome of Florometra sp. was 15,792 base pairs long and was composed of 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and three regions of unassigned sequence (UAS) including one putative control region. Unique nucleotide composition, a clear positive bias for T with an apparent loss of C in PCGs as observed in the Crinoidea mitogenomes, was also seen in the Florometra sp. mitogenome (45% T, 12% C). Phylogenetic analysis with the concatenated nucleotide sequences of entire PCGs of echinoderms confirmed that Florometra sp. is highly related to F. serratissima within the family Crinoidea.

[Effects of a video education program for patients with benign uterine tumors receiving high-intensity focused ultrasound treatment]. / ê³ ê°•ë„ 집속 초음파 치료를 받는 ìžê¶ì–‘ì„±ì¢ ì–‘ 환자의 동영상 교육프로그램 효과.

Purpose: The purpose of this study was to examine the effects of a video education program in women receiving high-intensity focused ultrasound (HIFU) treatment. Methods: This was a quasi-experimental study with a nonequivalent control group non-synchronized design. The participants were 54 patients who had benign uterine tumors and adenomyosis. The data were collected from June to August 2018. A 10-minute video education program on HIFU and post-procedural care was developed based on the literature. The experimental group was provided the video education program with a question-and-answer session for 10 minutes after viewing the video. The control group received usual care (i.e., verbal instructions on post-procedural self-care). The questionnaire survey was conducted twice: before the educational program and before being discharged from the hospital. Differences in uncertainty, emotions, and self-efficacy among patients were analyzed. Data were analyzed using the chi-square test, Shapiro-Wilk test, paired t-test, and t-test with SPSS version 23.0. Results: The participants in the experimental group showed a decrease in uncertainty(t=4.33, p<.001), improvements in anxiety(t=-4.07, p<.001) and depression (t=-3.55,p<.001), and an enhancement ofself-efficacy (t=-4.39,p<.001) compared to the control group. Conclusion: This nursing intervention was effective at reducing uncertainty, improving emotions, and enhancing self-efficacy. This intervention is feasible for use in nursing practice as an aid for patients when considering treatment methods.

Prolonged exposure to hypoxia inhibits the growth of Pacific abalone by modulating innate immunity and oxidative status.

In aquatic animals, hypoxia is associated with growth retardation, impaired immunity, susceptibility to pathogens, oxidative stress, and mortality. However, the relative long-term effects of hypoxia on bivalves, including abalone, are not well understood. In this study, we examined the effects of exposure to hypoxic (2.5 and 4 mg O2 L-1) and normoxic (8 mg O2 L-1) conditions on the growth, survival, and immune and antioxidant responses of the economically important Pacific abalone Haliotis discus hannai over a 4 month period. We observed that exposure to 2.5 mg O2 L-1 resulted in marked reductions in assessed shell parameters, average meat weight, and survival compared with exposure to 4 and 8 mg O2 L-1. There were also significant reductions in oxygen consumption and ammonia-N excretion in abalone exposed to 2.5 mg O2 L-1. We also detected initial immunosuppression in the 2.5 mg O2 L-1-treated abalone, as evidenced by a significant reduction in total hemocytes and inhibition of antibacterial and lysozyme activities. Furthermore, intracellular malondialdehyde concentrations were significantly elevated at 1 month in the 2.5 mg O2 L-1 treatment group, whereas there were reductions in the levels of glutathione and enzymatic activities of catalase and superoxide dismutase, thereby indicating potential hypoxia-induced oxidative stress and a depression of antioxidant capacity. After 4 months of treatment, severe hypoxia (2.5 mg O2 L-1) had significantly modulated all measured parameters, whereas exposure to 4 and 8 mg O2 L-1 had induced no significant effects. Collectively, our observations indicate that under long-term exposure to hypoxia, Pacific abalone failed to maintain an effective antioxidant defense system and adequate immunity, with the observed biochemical disruptions leading to a reduction in growth and survival.

[A study on job stress and the coping of ICU nurses].

PURPOSE: This study investigated job stress and coping of ICU Nurses. METHOD: Data was accumulated from 206 ICU nurses serving at least more than one year in 500 bed order hospitals during the period of three months from June 1, to August 30, 2006. RESULTS: The average job stress was 2.96 +/- .95 points, which was relatively high. The average coping was 2.55 +/- .23 points. CONCLUSION: The extent of the job stress of ICU nurses was relatively high, and they received the heaviest stress from job circumstances. For the prevention of job stress, every effort is required to analyze the causes of stress caused by job circumstances and to pose an appropriate solution. Meanwhile, job stress, needs to be controlled using a solution for the central problem, and search for social support.

[Prediction of perceived health status on job stress and family stress with middle school teachers].

PURPOSE: The purpose of this study was to identify the relationship among job stress, family stress and perceived health status of middle school teachers and to present basic information about promoting health and coping with stress. METHOD: Participants(N=547) was recruited in B city from November 2005 to December 2005. Data were analyzed with descriptive statistics, t-test, ANOVA, Pearson's correlation and multiple regression. RESULTS: The degree of job stress of the middle school teachers was 54.47 out of a total score of 88; that of family stress was 46.57 out of a total score of 96; and that of perceived health status was 78.59 out of the perfect score 100. There was a significantly negative relationship between job stress and perceived health status (r=-.274, p<.001), and family stress and perceived health status(r=-.408, p<.001). However, there was a positive relationship between job stress and family stress(r=.298, p<.001). Family stress, gender, charging subject, job stress, charging grade and number of family member was 27.1% of the variance in perceived health status of middle school teachers. CONCLUSION: Family stress has the most important impact on perceived health status with middle school teachers. Based on the finding, we could conclude that both job stress and family stress management should be required to improve perceived health status.

[A concept analysis of assertiveness].

PURPOSE: The purpose of this study was to analyze and clarify the meaning of the concept, assertiveness. METHOD: This study used Walker and Avant's process of concept analysis. RESULTS: 1. Attributes of assertiveness were defined as 1) Self-esteem 2) Comprehension to others 3) Clarification of the subject 4) Verbal communication 5) Non-verbal communication. 2. The antecedents of assertiveness consist of these facts 1) The occurrence of a conflict situation 2) The occurrence of will to stick to one's opinions. 3. There are consequences occurring as a result of assertiveness 1) Positive self-confidence 2) Increased comprehension or consideration to others 3) Expand of mutual respect 4) Maintenance of continuously cooperative relationship with each other 5) Output of acceptable results to each other. CONCLUSION: Assertiveness is a core human behavior and is key to interpersonal relationships. Using the components of the concept of assertiveness, many conflicts in a nursing situation can be effectively prevented.

[The effects of a rehabilitation program on physical health, physiological indicator and quality of life in breast cancer mastectomy patients].

PURPOSE: The purpose of this study was to investigate the effects of a rehabilitation program on physical health, physiological indicators and quality of life in breast cancer mastectomy patients. METHODS: The subjects included thirty-one patients with breast cancer (17 in the experimental group and 14 in the control group). The subjects in the experimental group participated in a rehabilitation program for 10 weeks, which was composed of an exercise program, teaching, counseling and support for 2 sessions per week. RESULTS: There was a significant increase in flexion, internal rotation and external rotation but no significant increase in extension in the experimental group compared to the control group. The total cholesterol, triglyceride, HDL, LDL, and CD56 in the experimental group compared to the control group was not significantly decreased after the rehabilitation program. Compared to the control group, quality of life in the experimental group was significantly improved and fatigue in that group was significantly decreased after the rehabilitation program. CONCLUSION: The 10-week rehabilitation program showed a large affirmative effect on physical health, physiological indicators and quality of life in breast cancer mastectomy patients.