Plausibility of Daphnia magna as an alternative experimental model to evaluate effects on eicosanoid synthesis.

Eicosanoids play important roles in inflammation, allergy, fever, and immune responses. In the eicosanoid pathway, cyclooxygenase (COX) catalyzes the conversion of arachidonic acid to prostaglandins and is a crucial target of nonsteroidal anti-inflammatory drugs (NSAIDs). Thus, toxicological studies on the eicosanoid pathway are important for drug discovery and the evaluation of adverse health outcomes due to environmental contaminants. However, experimental models are limited owing to concerns regarding ethical standards. Thus, new alternative models for evaluating toxic effects on the eicosanoid pathway must be developed. To this end, we adopted an invertebrate species, Daphnia magna, as an alternative model. D. magna was exposed to ibuprofen, a major NSAID, for 6 and 24 h. Transcription of eicosanoid-related genes (pla2, cox, pgd synthase, pgd2r2, ltb4dh, and lox) was analyzed by qPCR, eicosanoids (arachidonic acid, prostaglandin F2, dihydroxy prostaglandin F2, and 5-hydroxyeicosatetraenoate) were quantified by multiple reaction monitoring, and enzyme-linked immunosorbent assay was used to determine protein levels of arachidonic acid and prostaglandin E2 (PGE2). After 6 h of exposure, transcription of the pla2 and cox genes was downregulated. In addition, the whole-body level of arachidonic acid, an upstream of COX pathway, increased by over 1.5-fold. The levels of PGE2, a downstream of COX pathway, decreased after 24 h of exposure. According to our results, it is expected that the eicosanoid pathway might be conserved in D. magna, at least partially. This indicates the plausibility of D. magna as an alternative model for the screening of new drugs or chemical toxicity.

Loss of splicing factor IK impairs normal skeletal muscle development.

BACKGROUND: IK is a splicing factor that promotes spliceosome activation and contributes to pre-mRNA splicing. Although the molecular mechanism of IK has been previously reported in vitro, the physiological role of IK has not been fully understood in any animal model. Here, we generate an ik knock-out (KO) zebrafish using the CRISPR/Cas9 system to investigate the physiological roles of IK in vivo. RESULTS: The ik KO embryos display severe pleiotropic phenotypes, implying an essential role of IK in embryonic development in vertebrates. RNA-seq analysis reveals downregulation of genes involved in skeletal muscle differentiation in ik KO embryos, and there exist genes having improper pre-mRNA splicing among downregulated genes. The ik KO embryos display impaired neuromuscular junction (NMJ) and fast-twitch muscle development. Depletion of ik reduces myod1 expression and upregulates pax7a, preventing normal fast muscle development in a non-cell-autonomous manner. Moreover, when differentiation is induced in IK-depleted C2C12 myoblasts, myoblasts show a reduced ability to form myotubes. However, inhibition of IK does not influence either muscle cell proliferation or apoptosis in zebrafish and C2C12 cells. CONCLUSION: This study provides that the splicing factor IK contributes to normal skeletal muscle development in vivo and myogenic differentiation in vitro.

Characterization of Decellularized Plant Leaf as an Emerging Biomaterial Platform.

Decellularized plants have emerged as promising biomaterials for cell culture and tissue engineering applications due to their distinct material characteristics. This study explores the biochemical, mechanical, and structural properties of decellularized leaves that make them useful as biomaterials for cell culture. Five monocot leaf species were decellularized via alkali treatment, resulting in the effective removal of DNA and proteins. The Van Soest method was used to quantitatively evaluate the changes in cellulose, hemicellulose, and lignin content during decellularization. Tensile tests revealed considerable variations in mechanical strength depending on the plant species, the decellularization state, and the direction of applied mechanical force. Decellularized monocot leaves exhibited a notable reduction in mechanical strength and anisotropic properties depending on the leaf orientation. Imaging revealed inherent microgrooves on the epidermis of the monocot leaves. Permeability studies, including water uptake and biomolecule transport through decellularized leaves, confirmed excellent water uptake capability but limited biomolecule transport. Lastly, the plants were enzymatically degradable using typical plant enzymes, which were minimally cytotoxic to mammalian cells. Taken together, the features of decellularized plant leaves characterized in this study suggest ways in which they can be useful in cell culture and tissue engineering applications.

IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene, ofd1.

BACKGROUND: The cilia are microtubule-based organelles that protrude from the cell surface. Abnormalities in cilia result in various ciliopathies, including polycystic kidney disease (PKD), Bardet-Biedl syndrome (BBS), and oral-facial-digital syndrome type I (OFD1), which show genetic defects associated with cilia formation. Although an increasing number of human diseases is attributed to ciliary defects, the functions or regulatory mechanisms of several ciliopathy genes remain unclear. Because multi ciliated cells (MCCs) are especially deep in vivo, studying ciliogenesis is challenging. Here, we demonstrate that ik is essential for ciliogenesis in vivo. RESULTS: In the absence of ik, zebrafish embryos showed various ciliopathy phenotypes, such as body curvature, abnormal otoliths, and cyst formation in the kidney. RNA sequencing analysis revealed that ik positively regulated ofd1 expression required for cilium assembly. In fact, depletion of ik resulted in the downregulation of ofd1 expression with ciliary defects, and these ciliary defects in ik mutants were rescued by restoring ofd1 expression. Interestingly, ik affected ciliogenesis particularly in the proximal tubule but not in the distal tubule in the kidney. CONCLUSIONS: This study demonstrates the role of ik in ciliogenesis in vivo for the first time. Loss of ik in zebrafish embryos displays various ciliopathy phenotypes with abnormal ciliary morphology in ciliary tissues. Our findings on the ik-ofd1 axis provide new insights into the biological function of ik in clinical ciliopathy studies in humans.

The effects of medical students' self-oriented perfectionism on academic procrastination: the mediating effect of fear of failure.

PURPOSE: Based on the logic that self-oriented perfectionism (SOP) is one of the most well-established predictors of academic procrastination (AP), we predicted that fear of failure (FF) would mediate the association between SOP and AP. The purpose of this study is to investigate the mediating effect of FF on the influence of SOP on AP in medical students. METHODS: A total of 156 undergraduate medical students completed a battery of questionnaires. This study is an analysis of cross-sectional data obtained through an offline survey. The self-report questionnaires assessed demographics and psychological scales, including the Multidimensional Perfectionism Scale, Performance Failure Appraisal Inventory, and Aitken Procrastination Inventory. The data were analyzed by descriptive statistics, correlations analysis, and multiple regression analyses using IBM SPSS ver. 22.0 (IBM Corp., Armonk, USA). RESULTS: SOP had a direct negative influence on AP (ß=-0.420, p<0.001). Also, SOP had a significant indirect effect on AP through FF (ß=0.0393; 95% confidence interval, 0.040-0.0936). These results indicated that the FF partially mediates the relationship between SOP and AP. CONCLUSION: Although SOP among medical students might play an adaptive role to lessen AP, in cases FF gets higher, SOP could have opposing effects via the mediating effect of FF, leading to an actual increase in AP. Attempts to deal with the FF among medical students should be made for better academic achievements.

Effects of Electroencephalogram Biofeedback on Emotion Regulation and Brain Homeostasis of Late Adolescents in the COVID-19 Pandemic.

PURPOSE: The purpose of this study was to examine the effects of electroencephalogram (EEG) biofeedback training for emotion regulation and brain homeostasis on anxiety about COVID-19 infection, impulsivity, anger rumination, meta-mood, and self-regulation ability of late adolescents in the prolonged COVID-19 pandemic situation. METHODS: A non-equivalent control group pretest-posttest design was used. The participants included 55 late adolescents in the experimental and control groups. The variables were evaluated using quantitative EEG at pre-post time points in the experimental group. The experimental groups received 10 sessions using the three-band protocol for five weeks. The collected data were analyzed using the Shapiro-Wilk test, Wilcoxon rank sum test, Wilcoxon signed-rank test, t-test and paired t-test using the SAS 9.3 program. The collected EEG data used a frequency series power spectrum analysis method through fast Fourier transform. RESULTS: Significant differences in emotion regulation between the two groups were observed in the anxiety about COVID-19 infection (W = 585.50, p = .002), mood repair of meta-mood (W = 889.50, p = .024), self-regulation ability (t = -5.02, p < .001), self-regulation mode (t = -4.74, p < .001), and volitional inhibition mode (t = -2.61, p = .012). Neurofeedback training for brain homeostasis was effected on enhanced sensory-motor rhythm (S = 177.00, p < .001) and inhibited theta (S = -166.00, p < .001). CONCLUSION: The results demonstrate the potential of EEG biofeedback training as an independent nursing intervention that can markedly improve anxiety, mood-repair, and self-regulation ability for emotional distress during the COVID-19 pandemic.

Voluntary peer-mentoring program for undergraduate medical students: exploring the experiences of mentors and mentees.

PURPOSE: We aimed to examine the participants' satisfaction and evaluation of the program's appropriateness, outcomes and benefits from participants' perspectives and gather suggestions from students to improve peer mentor programs. METHODS: From 2016 to 2018, 67 mentees and mentors participated in the peer mentoring program. All program participants were asked to participate in the survey, and the respondents were invited to focus group interview (FGI). Quantitative data was collected from the survey questionnaire. Qualitative data was gathered from the open-end questions in the survey and supplemented from additional semi-structured FGIs. The interview data were analyzed using qualitative content analysis. RESULTS: Nineteen responded to the survey, and six participated in the further FGI. Qualitative data contained outcomes and mutual benefits, factors for mentoring success, negative experiences, and suggestions for improvement. Especially factors for mentoring success consisted of various methods of studying assistance, motivation, autonomy, responsibility, emotional support, and relational bonding as important topics concerning mentor-mentee experiences. The satisfaction scores about the program appropriateness, others' attitudes, program implementation, ranged from 3.5 to 3.9 (5-point Likert scores) without significant difference between mentors and mentees. The only negative experience reported by a mentee was feeling the pressure. Specific guidelines on program implementation, pre-education for mentees, appropriate matching, and mentees' clear purpose and spontaneity were suggested to improve the program. CONCLUSION: Participants were generally satisfied with the peer mentoring program, gaining academic and non-academic achievements, including emotional support and improved relationships. Furthermore, we expect that this program can be improved with participants' suggestions in the future.

Rutin inhibits DRP1-mediated mitochondrial fission and prevents ethanol-induced hepatotoxicity in HepG2 cells and zebrafish.

Excessive alcohol consumption causes the cellular and tissue damage. The toxic metabolites of ethanol are harmful to multiple organ systems, such as the central nervous system, skeletal muscles, and liver, and cause alcohol-induced diseases like cancer, as well as induce hepatotoxicity, and alcoholic myopathy. Alcohol exposure leads to a surge in hepatic alcohol metabolism and oxygen consumption, a decrease in hepatic ATP, and the rapid accumulation of lipid within hepatocytes. Several pathologies are closely linked to defective mitochondrial dynamics triggered by abnormal mitochondrial function and cellular homeostasis, raising the possibility that novel drugs targeting mitochondrial dynamics may have therapeutic potential in restoring cellular homeostasis in ethanol-induced hepatotoxicity. Rutin is a phytochemical polyphenol known to protect cells from cytotoxic chemicals. We investigated the effects of rutin on mitochondrial dynamics induced by ethanol. We found that rutin enhances mitochondrial dynamics by suppressing mitochondrial fission and restoring the balance of the mitochondrial dynamics. Mitochondrial elongation following rutin treatment of ethanol exposed cells was accompanied by reduced DRP1 expression. These data suggest that rutin plays an important role in remodeling of mitochondrial dynamics to alleviate hepatic steatosis and enhance mitochondrial function and cell viability.

Underweight body mass index as a predictive factor for surgical site infections after laparoscopic appendectomy.

PURPOSE: Analyses of risk factors associated with surgical site infections (SSIs) after laparoscopic appendectomy (LA) have been limited. Especially, the association of an underweight body mass index (BMI) with SSIs has not been clearly defined. This study aimed to identify the impact of underweight BMI in predicting SSIs after LA. MATERIALS AND METHODS: The records of a total of 101 consecutive patients aged ≥16 years who underwent LA by a single surgeon between March 2011 and December 2012 were retrieved from a prospectively collected database. The rate of SSIs was compared among the underweight, normal and overweight and obese groups. Also, univariate and multivariate analyses were performed to identify the factors associated with SSIs. RESULTS: The overall rate of SSIs was 12.8%. The superficial incisional SSI rate was highest in the underweight group (44.4% in the underweight group, 11.0% in the normal group, and 0% in the overweight and obese group, p=0.006). In univariate analysis, open conversion and being underweight were determined to be risk factors for SSIs. Underweight BMI was also found to be a significant predictor for SSIs in multivariate analysis (odds ratio, 10.0; 95% confidence interval, 2.0-49.5; p=0.005). CONCLUSION: This study demonstrated underweight BMI as being associated with SSIs after LA. Surgeons should be more cautious to prevent SSIs in patients that are underweight when performing LA.