Exploring the gap between school of nursing theoretical foundations and clinical practice.

BACKGROUND: Theoretical and practical preparation is essential for developing competent nurses. The clinical setting is the most effective context for learning nursing skills. It gives opportunities for newly qualified nurses to practice clinical decision-making by applying theoretical knowledge. Integrating theory and clinical practice with good supervision improves newly qualified nurses' competencies to care for patients and enhance their self-confidence. OBJECTIVE: To identify the gaps between theoretical preparation in the schools of nursing and actual hospital clinical work in a public hospital in Bahrain and to suggest possible solutions to overcome these gaps. METHODS: A qualitative descriptive study design was used in a tertiary public hospital in Bahrain. Ten newly employed registered nurses were recruited using purposive sampling. Semi-structured interviews were conducted, and a thematic analysis was employed. RESULTS: Two Over-arching themes emerged from the analysis of the responses. The first identified the causes of the gaps that new nurses face in the transition (Lack of autonomy, technology employed in healthcare settings, impact of the COVID-19 pandemic, and lack of clinical exposure). The second provided possible solutions for these gaps (Open communication and collaboration, orientation phase and preceptorship, empowerment and self-confidence, and more clinical exposure). CONCLUSIONS: Good collaboration between schools of nursing and healthcare care organizations can incorporate suggested solutions given by the study participants to reduce the identified gaps.

Construct validity of a questionnaire for measuring student engagement in problem-based learning tutorials.

BACKGROUND: Student engagement is student investment of time and energy in academic and non-academic experiences that include learning, teaching, research, governance, and community activities. Although previous studies provided some evidence of measuring student engagement in PBL tutorials, there are no existing quantitative studies in which cognitive, behavioral, and emotional engagement of students in PBL tutorials is measured. Therefore, this study aims to develop and examine the construct validity of a questionnaire for measuring cognitive, behavioral, and emotional engagement of students in PBL tutorials. METHODS: A 15-item questionnaire was developed guided by a previously published conceptual framework of student engagement. Focus group discussion (n = 12) with medical education experts was then conducted and the questionnaire was piloted with medical students. The questionnaire was then distributed to year 2 and 3 medical students (n = 176) in problem-based tutorial groups at the end of an integrated course, where PBL is the main strategy of learning. The validity of the internal structure of the questionnaire was tested by confirmatory factor analysis using structural equation modeling assuming five different models. Predictive validity evidence of the questionnaire was studied by examining the correlations between students' engagement and academic achievement. RESULTS: Confirmatory factor analysis indicates a good fit between the measurement and structural model of an 11-item questionnaire composed of a three-factor structure: behavioral engagement (3 items), emotional engagement (4 items), and cognitive engagement (4 items). Models in which the three latent factors were considered semi-independent provided the best fit. The construct reliabilities of behavioral, cognitive, and emotional factors were 0.82, 0.82, and 0.76, respectively. We failed however to find significant relationships between academic achievement and engagement. CONCLUSIONS: We found a strong evidence to support the construct validity of a three-factor structure of student engagement in PBL tutorial questionnaire. Further studies are required to test the validity of this instrument in other educational settings. The predictive validity is another area needing further scrutiny.

Readiness for Interprofessional Learning Among Students of Four Undergraduate Health Professions Education Programs.

Background: In interprofessional learning, students from different professions learn about, from, and with each other so that they can collaborate effectively, deliver high-quality healthcare, and achieve positive health outcomes. This study aimed to explore the readiness of students from four health professions education programs for interprofessional learning. Methods: A cross-sectional descriptive study was carried out on 339 students. The Readiness for Interprofessional Learning Scale (RIPLS) was used to collect data. Descriptive statistics were used. Paired-samples t-test and ANOVA test were used to compare the responses of participants. Correlations between dependent and independent variables were explored by Pearson's correlation test. The statistical significance level was set at p < 0.05. Results: The reliability study of the collected data showed excellent internal consistency (Cronbach's ɑ = 0.819). Results revealed a statistically significant difference between the responses of students from the four programs regarding the "Roles and Responsibilities" subscale (p = 0.000). A statistically significant difference between male and female students regarding two statements within the "Teamwork and Collaboration" subscale and one statement within the "Negative Professional Identity" subscale (p < 0.05) was also detected. The correlation study showed a weak but statistically significant correlation between RIPLS mean scores and the students' study program (p < 0.015). Conclusion: In conclusion, the students showed readiness for IPL as evidenced by their positive perception of the interprofessional learning concepts.

Sensitivity and specificity of microRNA-204, CA125, and CA19.9 as biomarkers for diagnosis of ovarian cancer.

BACKGROUND: Ovarian cancer is usually detected at later stages and no effective screening approach, has been identified. Therefore, sensitive and specific biomarkers for detecting ovarian cancer are urgently needed. OBJECTIVE: This study aimed to investigate the efficacy of six biomarkers for the early clinical diagnosis of ovarian cancer. SUBJECTS & METHODS: The study included 120 patients (benign ovarian tumors and early and late ovarian carcinoma) and 30 control healthy volunteers. MiRNA-204, CA125, CA19.9, hepcidin, microfibril-associated glycoprotein 2, and ferroportin levels were determined in all patients and control volunteers. RESULTS: The combined area under the receiver operating characteristic curves for miRNA-204, CA125, and CA19.9 were 0.938, 1.000, and 0.998 for benign tumors and early and late ovarian carcinomas, respectively. The sensitivities of miRNA-204, CA125, and CA19.9 were 98.04%, 100.00%, and 96.19% and the specificities were 58.33%, 62.50%, and 57.78%, respectively. CONCLUSION: The positive predictivity of miRNA-204, CA125, and CA19.9 for ovarian cancer is high (59.57%, 58.24%, and 61.67%, respectively). Thus, the combination of these three biomarkers is a good diagnostic tool for ovarian cancer.

Comparative study of phenolic profile, antioxidant and antimicrobial activities of aqueous extract of white and green tea.

The sole difference between white tea (WT) and green tea (GT) is the former that made only from the buds and young leaves of the Camelia sinensis plant, whilst the latter is made from matured tea leaves. The phytochemical profiles, phenolic compounds, antioxidant, and antimicrobial activity of two varieties of Camellia sinensis teas, white and green, were compared in this study. Total antioxidant capacity, reducing power, DPPH radical scavenging, and Fe+2 chelating activities were used to determine antioxidant activities in water extract of GT and WT. The largest level of phenolic content was discovered in WGTE compared with the lowest amount was found in WWTE (290.67 mg/100 g tea and 185.96 mg/100 g tea, respectively). Phenoilc acids (gallic, benzoic, chlorogenic, ellagic, and ρ-coumaric acids) and flavonoids (rutin and kampherol) were found in the two extracts. The findings of DPPH radical scavenging assays were 84.06 and 82.37% inhibition. In vitro antimicrobial activity was indicated that (WWTE and WGTE) had a high level of activity against Staphylococcus aureus, and gave negative activity against Salmonella typhimurium, and Aspergillus Niger. The WT and GT extracts are a great source of natural antioxidants with biological effects on human health.

Novel quercetin encapsulated chitosan functionalized copper oxide nanoparticles as anti-breast cancer agent via regulating p53 in rat model.

This study was designed to present a new quercetin encapsulated chitosan functionalized copper oxide nanoparticle (CuO-ChNPs-Q) and assessed its anti-breast cancer activity both in vitro and in vivo. The CuO-ChNPs-Q may act as anti-proliferating agent against DMBA-induced mammary carcinoma in female rats. The CuONPs was functionalized with chitosan then quercetin was conjugated with them producing CuO-ChNPs-Q, then characterized. The in vitro anti-proliferating activity of the CuO-ChNPs-Q was evaluated against three human cell line. Then, the anti-breast cancer effect of the CuO-ChNPs-Q was assessed against DMBA-induction compared to both CuONPs and Q in female rat model. The in vitro results proved the potent anticancer activity of the CuO-ChNPs-Q compared to CuONPs and quercetin. The in vivo data showed significant reduction in breast tumors of DMBA-induced rats treated with CuO-ChNPs-Q compared to CuONPs and Q. The CuO-ChNPs-Q treatment had induced apoptosis via increased p53 gene, arrested the cell-cycle, and increased both cytochrome c and caspase-3 levels leading to mammary carcinoma cell death. Also, the CuO-ChNPs-Q treatment had suppressed the PCNA gene which decreased the proliferation of the mammary carcinoma cells. In conclusion, the CuO-ChNPs-Q might be a promising chemotherapeutic agent for treatment of breast cancer with a minimal toxicity on vital organs.

Genotype-phenotype correlation of 33 patients with maple syrup urine disease.

Maple syrup urine disease (MSUD) is a rare autosomal recessive inherited disorder due to defects in the branched-chain α-ketoacid dehydrogenase complex (BCKDC). MSUD varies in severity and its clinical spectrum is quite broad, ranging from mild to severe phenotypes. Thirty-three MSUD patients were recruited into this study for molecular genetic variant profiling and genotype-phenotype correlation. Except for one patient, all other patients presented with the classic neonatal form of the disease. Seventeen different variants were detected where nine were novel. The detected variants spanned across the entire BCKDHA, BCKDHB and DBT genes. All variants were in homozygous forms. The commonest alterations were nonsense and frameshift variants, followed by missense variants. For the prediction of variant's pathogenicity, we used molecular modeling and several in silico tools including SIFT, Polyphen2, Condel, and Provean. In addition, six other tools were used for the prediction of the conservation of the variants' sites including Eigen-PC, GERP++, SiPhy, PhastCons vertebrates and primates, and PhyloP100 rank scores. Herein, we presented a comprehensive characterization of a large cohort of patients with MSUD. The clinical severity of the variants' phenotypes was well correlated with the genotypes. The study underscores the importance of the use of in silico analysis of MSUD genotypes for the prediction of the clinical outcomes in patients with MSUD.

Upregulation of long noncoding RNA Lnc-IRF2-3 and Lnc-ZNF667-AS1 is associated with poor survival in B-chronic lymphocytic leukemia.

BACKGROUND: Lnc-IRF2-3 and Lnc-ZNF667-AS1 were recently studied as a positive biomarker for many tumor cells. However, experimental studies found that they are associated with worse outcomes in B-CLL. METHODS: A prospective case study was conducted on 135 B-CLL patients that were compared to thirty healthy controls. The patients were followed up for 40 months and quantitative measurements of Lnc-IRF2-3 and Lnc-ZNF667-AS1 were measured and compared between the two groups as well as high-risk and low low-risk B-CLL. RESULTS: Lnc-IRF2-3 and Lnc-ZNF667-AS1 had a high specificity (94% and 85%) and sensitivity (85%, 87%), respectively, to differentiate B-CLL from healthy controls. Furthermore, they showed high expression levels in high-risk CLL groups. For survival analysis, there was a negative correlation between overall survival (OS) and progression-free survival (PFS) and both biomarkers. However, it was not evident in multivariate Cox regression analysis; in patients with Lnc-IRF2-3 expression level, >67 had a significant decrease in OS and PFS. However, there is no significant effect for high expression levels of Lnc-ZNF667-AS1 on OS (P = .16) or PFS (P = .48). CONCLUSION: The Lnc-IRF2-3 and Lnc-ZNF667-AS1 are promising prognostic biomarkers in B-CLL.

Assessment of the association of serum progranulin with autophagy in diabetic patients.

INTRODUCTION: Progranulin (PGRN) has newly arisen as an important regulatory protein of glucose metabolism and insulin sensitivity. Progranulin expression is interrelated with lysosomal function strongly linked to autophagy pathway. We aimed to evaluate the correlation between PGRN protein and microtubule-associated protein light chain 3B (LC3B) expression level in diabetic patients. MATERIAL AND METHODS: Blood samples of 70 type 2 diabetic Egyptian patients were provided for analysis of concentrations of serum progranulin and interleukin 6 (IL-6) using ELISA, and quantifying expression of LC3B RNA level using qPCR. A group of 20 healthy volunteers were also enrolled. RESULTS: Serum levels of PGRN and IL-6 as well as LC3B gene expression levels were markedly higher in type 2 diabetic patients. Additionally, our study revealed a cut-off value of 18.14 ng/mL for progranulin serum level and 3.23 for LC3B expression level, with sensitivities of 83.6% and 75.4% and specificities of 83.8% and 58.3%, respectively. Circulating PGRN levels are positively correlated with body mass index (BMI), glucose concentration, and IL-6. CONCLUSION: Our results support the hypothesis that progranulin is introduced as a novel marker of chronic inflammatory response in type 2 diabetes that aggravates insulin resistance via activated autophagy, indicating the importance of this novel adipokine in the regulation of glucose metabolism and as a promising therapeutic target in the treatment of diabetes. KEY WORDS: diabetes; progranulin; autophagy; microtubule-associated proteins light chain 3B; interleukin 6.

Synergistic Effect of α-Solanine and Cisplatin Induces Apoptosis and Enhances Cell Cycle Arrest in Human Hepatocellular Carcinoma Cells.

AIM: The clinical application of cisplatin is limited by severe side effects associated with high applied doses. The synergistic effect of a combination treatment of a low dose of cisplatin with the natural alkaloid α-solanine on human hepatocellular carcinoma cells was evaluated. METHODS: HepG2 cells were exposed to low doses of α-solanine and cisplatin, either independently or in combination. The efficiency of this treatment modality was evaluated by investigating cell growth inhibition, cell cycle arrest, and apoptosis enhancement. RESULTS: α-solanine synergistically potentiated the effect of cisplatin on cell growth inhibition and significantly induced apoptosis. This synergistic effect was mediated by inducing cell cycle arrest at the G2/M phase, enhancing DNA fragmentation and increasing apoptosis through the activation of caspase 3/7 and/or elevating the expression of the death receptors DR4 and DR5. The induced apoptosis from this combination treatment was also mediated by reducing the expression of the anti-apoptotic mediators Bcl-2 and survivin, as well as by modulating the miR-21 expression. CONCLUSION: Our study provides strong evidence that a combination treatment of low doses of α-solanine and cisplatin exerts a synergistic anticancer effect and provides an effective treatment strategy against hepatocellular carcinoma.

Pterocarpus santalinus ameliorates streptozotocin-induced diabetes mellitus via anti-inflammatory pathways and enhancement of insulin function.

OBJECTIVES: Morbidity and mortality due to diabetes mellitus (DM) result in exorbitant psycho-economical costs, so there is a strong need to create new strategies and drugs for controlling DM. The aim of the current study was to investigate the anti-diabetic effect of the aqueous extract of Pterocarpus santalinus on streptozotocin (STZ)-induced DM as compared to glustin. MATERIALS AND METHODS: Thirty male rats were divided into five groups of six rats each as follows: control; the second group, received the aqueous plant extract (250 mg/kg) orally and daily for three weeks; the third group, was intraperitoneally injected with a single dose of 65 mg/kg of STZ and sacrificed after four weeks; the fourth and fifth groups, were injected with STZ, then after one week these were treated orally with either plant extract or with 3 mg/kg of glustin for three weeks, then sacrificed. RESULTS: HPLC analysis of the plant aqueous extract showed that it contains many polyphenols and flavonoids. Treatment with STZ resulted in significant reductions in body weight, insulin level, and the expression of Fetuin-A and IRS-1. It also caused significant elevations in glucose, HOMA-IR, glycated hemoglobin, urea, and the expression of JNK and SIRT-1. STZ also caused an extensive ß-cell degranulation and decreased cellular density. The aqueous extract of red sandalwood was able to abrogate the deleterious effects caused by STZ and improved the histological architecture of pancreas. CONCLUSION: The aqueous extract of P. santalinus ameliorates diabetes mellitus via anti-inflammatory pathways and enhancement of insulin function.

An unconventional RNA-based thermosensor within the 5' UTR of Staphylococcus aureus cidA.

Staphylococcus aureus is a Gram-positive bacterial pathogen of global concern and a leading cause of bacterial infections worldwide. Asymptomatic carriage of S. aureus on the skin and in the anterior nares is common and recognized as a predisposing factor to invasive infection. Transition of S. aureus from the carriage state to that of invasive infection is often accompanied by a temperature upshift from approximately 33°C to 37°C. Such a temperature shift is known in other pathogens to influence gene expression, often resulting in increased production of factors that promote survival or virulence within the host. One mechanism by which bacteria modulate gene expression in response to temperature is by the regulatory activity of RNA-based thermosensors, cis-acting riboregulators that control translation efficiency. This study was designed to identify and characterize RNA-based thermosensors in S. aureus. Initially predicted by in silico analyses of the S. aureus USA300 genome, reporter-based gene expression analyses and site-specific mutagenesis were performed to demonstrate the presence of a functional thermosensor within the 5' UTR of cidA, a gene implicated in biofilm formation and survival of the pathogen. The nucleic sequence composing the identified thermosensor are sufficient to confer temperature-dependent post-transcriptional regulation, and activity is predictably altered by the introduction of site-specific mutations designed to stabilize or destabilize the structure within the identified thermosensor. The identified regulator is functional in both the native bacterial host S. aureus and in the distally related species Escherichia coli, suggesting that its regulatory activity is independent of host-specific factors. Interestingly, unlike the majority of bacterial RNA-based thermosensors characterized to date, the cidA thermosensor facilitates increased target gene expression at lower temperatures. In addition to the characterization of the first RNA-based thermosensor in the significant pathogen S. aureus, it highlights the diversity of function within this important class of ribo-regulators.

IL-28ß gene polymorphism determines virological response to PEGylated interferon therapy in hepatitis C virus genotype 4 Egyptian patients.

BACKGROUND: PEGylated interferon (PEG-IFN) in combination with ribavirin is the gold standard for chronic hepatitis C virus (HCV). The majority of patients received PEG-IFN/ribavirin achieve a sustained viral response (SVR), but few cases failed to respond. It was evident that host genetic factors determine the treatment-induced viral clearance as well as spontaneous response. In the current study, the rs12979860 polymorphism of IL28ß gene was analyzed and its association with the virological response to PEG-IFN treatment was determined. METHODS: One hundred and fifty Egyptian patients with HCV genotype 4 treated with PEG-IFN/ribavirin were assessed at 12 and 24 weeks of therapy, the rs12979860 genotype was determined using TaqMan-based quantitative polymerase chain reaction. RESULTS: Although the CC genotype was the most frequent (58%), the higher SVR was achieved for patients with favorable CC genotype (93%) in contrast to CT and TT genotypes. CONCLUSION: we conclude that IL28B polymorphism is highly associated with SVR to therapy in the Egyptian population infected with HCV genotype 4 and patients who carry CC genotype have a higher chance of SVR.

Sexual Functions in Male and Female Patients With Bipolar Disorder During Remission.

INTRODUCTION: Bipolar disorder is an episodic mood disorder that causes unusual shifts in mood and affects the ability to carry out day-to-day tasks. AIM: Evaluation of the sexual function in men and women with bipolar disorder during remission. METHODS: 60 men and women with bipolar disorder and 60 age-matched control subjects were included. A Structured Clinical Interview of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition was performed to confirm the diagnosis, and Hamilton Depression Rating Scale (HAM-D) to assess the depressive symptoms and Young Mania Rating Scale (YMRS) to assess the manic symptoms. We assessed sexual function in both sexes using international indices of erectile function for men and sexual function of women. MAIN OUTCOME MEASURES: Scores of HAM-D, YMRS, Arabic versions of International Index of Erectile Function (IIEF) and female sexual function (FSFI). RESULTS: Depressive symptoms showed insignificant adverse correlation with the IIEF in men, whereas they revealed adverse significant correlations with the items of female sexual function index (FSFI) except pain (correlation coefficients [r] = 0.349 [P = .059], r = 0.680 [P < .001], r = 0.574 [P = .001], r = 0.517 [P = .003], r = 0.569 [P = .001], r = 0.532 [P = .002], r = 0.609 [P < .001], r = 0.342 [P = .065], respectively). Interestingly, the manic symptoms were associated with sexual hyperfunctioning in the men and were insignificantly correlated with the different items of FSFI in the women (r = 0.414 [P = .023], r = 0.043 [P = .821], r = 0.100 [P = .601], r = 0.108 [P = .571], r = 0.183 [P = .332), r = 0.086 [P = .651], r = 0.022 (P = .907), r = 0.109 [P = .565], respectively). There was a positive correlation between the affected women's satisfaction and their partners' score (r = 0.374, P =.042). Finally, the mean score of pain was statistically higher in the female cases than the normal ones (mean ± SD = 3.6 ± 0.4, 3.4, ± 0.6; P = .036). CLINICAL IMPLICATIONS: A different approach may be mandatory for manic female patients. STRENGTHS & LIMITATIONS: This study is one of the few studies that evaluated the sexual function in patients with bipolar disorder especially during remission. Some limitations of this study must be mentioned. We failed to evaluate the female partners of the diseased males. Quality of life of the recruited patients was not assessed. Finally, the study included patients who were not drug free. CONCLUSION: Manic symptoms in female bipolar I patients are associated with sexual hypofunctioning. Elkhiat YI, Seif AFA, Khalil MA, et al. Sexual functions in male and female patients with bipolar disorder during remission. J Sex Med 2018;15:1111-1116.

Lecturing skills as predictors of tutoring skills in a problem-based medical curriculum.

PURPOSE: Recruitment of tutors to work in problem-based learning (PBL) programs is challenging, especially in that most of them are graduated from discipline-based programs. Therefore, this study aims at examining whether lecturing skills of faculty could predict their PBL tutoring skills. METHODS: This study included evaluation of faculty (n=69) who participated in both tutoring and lecturing within particular PBL units at the College of Medicine and Medical Sciences (CMMS), Arabian Gulf University, Bahrain. Each faculty was evaluated by medical students (n=45±8 for lecturing and 8±2 for PBL tutoring) using structured evaluation forms based on a Likert-type scale (poor to excellent). The prediction of tutoring skills using lecturing skills was statistically analyzed using stepwise linear regression. RESULTS: Among the parameters used to judge lecturing skills, the most important predictor for tutoring skills was subject matter mastery in the lecture by explaining difficult concepts and responding effectively to students' questions. Subject matter mastery in the lecture positively predicted five tutoring skills and accounted for 25% of the variance in overall effectiveness of the PBL tutors (F=22.39, P=0.000). Other important predictors for tutoring skills were providing a relaxed class atmosphere and effective use of audiovisual aids in the lecture. CONCLUSION: Predicting the tutoring skills based on lecturing skills could have implications for recruiting tutors in PBL medical programs and for tutor training initiatives.

Flaxseed suppressed prostatic epithelial proliferation in a rat model of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH), a disease occurring frequently among elderly males, is a slow progressive enlargement of the fibromuscular and epithelial structures of the prostate gland. Dietary factors may influence the prostate and exert an influence on prostatic growth and disease. The current study was undertaken to investigate the protective effect of dietary flaxseed supplementation against testosterone-induced prostatic hyperplasia in male rats. Forty male Wistar rats were divided into 5 groups: (1) untreated control; (2) treatment with testosterone propionate (TP) to induce prostate enlargement; (3) TP-treated group fed a diet containing 5% milled flaxseed; (4) TP-treated group fed a diet containing 10% milled flaxseed; and (5) TP-treated group fed a diet containing 20 ppm finasteride. Treatment with TP significantly increased the absolute and relative weights of different prostatic lobes, serum testosterone (T), and testosterone/estradiol ratio, as well as prostatic vascular endothelial growth factor (VEGF) expression, RNA synthesis per cell, and epithelial cell proliferation, detected as Ki67 labeling. Histopathological examination did not reveal marked differences in acinar morphology in ventral prostate, whereas morphometric analysis showed significantly increased epithelial cell height. Co-administration of flaxseed or finasteride with TP significantly reduced prostatic VEFG, epithelial cell proliferation, and RNA/DNA ratio, along with a significant increase in serum T and testosterone/estradiol ratio compared with TP-only-treated rats. Our results indicate that flaxseed, similar to the 5α-reductase inhibitor finasteride, blocked TP-induced prostate enlargement in a rat model of BPH, likely through suppression of prostatic VEFG and cellular proliferation.

Umbelliferone and daphnetin ameliorate carbon tetrachloride-induced hepatotoxicity in rats via nuclear factor erythroid 2-related factor 2-mediated heme oxygenase-1 expression.

Among various phytochemicals, coumarins comprise a very large class of plant phenolic compounds that have good nutritive value, in addition to their antioxidant effects. The purpose of the present study was to investigate the protective effects of two coumarin derivatives, umbelliferone and daphnetin, against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats and elucidate the underlying mechanism. Treatment of rats with either umbelliferone or daphnetin significantly improved the CCl4-induced biochemical alterations. In addition, both compounds alleviated the induced-lipid peroxidation and boosted the antioxidant defense system. Moreover, the investigated compounds attenuated CCl4-induced histopathological alterations of the liver. Finally, umbelliferone and daphnetin induced the nuclear translocation of the nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), thereby inducing the expression and activity of the cytoprotective heme oxygenase-1 (HO-1). These results suggest that umbelliferone and daphnetin ameliorate oxidative stress-related hepatotoxicity via their ability to augment cellular antioxidant defenses by activating Nrf2-mediated HO-1 expression.