TarFisDock: a web server for identifying drug targets with docking approach

TarFisDock is a web-based tool for automating the procedure of searching for small molecule–protein interactions over a large repertoire of protein structures. It offers PDTD (potential drug target database), a target database containing 698 protein structures covering 15 therapeutic areas and a reverse ligand–protein docking program. In contrast to conventional ligand–protein docking, reverse ligand–protein docking aims to seek potential protein targets by screening an appropriate protein database. The input file of this web server is the small molecule to be tested, in standard mol2 format; TarFisDock then searches for possible binding proteins for the given small molecule by use of a docking approach. The ligand–protein interaction energy terms of the program DOCK are adopted for ranking the proteins. To test the reliability of the TarFisDock server, we searched the PDTD for putative binding proteins for vitamin E and 4H-tamoxifen. The top 2 and 10% candidates of vitamin E binding proteins identified by TarFisDock respectively cover 30 and 50% of reported targets verified or implicated by experiments; and 30 and 50% of experimentally confirmed targets for 4H-tamoxifen appear amongst the top 2 and 5% of the TarFisDock predicted candidates, respectively. Therefore, TarFisDock may be a useful tool for target identification, mechanism study of old drugs and probes discovered from natural products. TarFisDock and PDTD are available at

Transiently Impaired Endothelial Function During Thyroid Hormone Withdrawal in Differentiated Thyroid Cancer Patients

PURPOSE: Endothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy. METHODS: We recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the day before thyroxine withdrawal(P RESULTS: We analyzed the changes of FMD, thyroid function and lipids at three time points. FMD(P CONCLUSION: Endothelial function was transiently impaired in DTC patients at short-term hypothyroidism state during the RAI therapy, and immediately returned to the initial state after restoring TSH suppression therapy

Effect of acetone extract of Rumex japonicas Houtt on hydrogen peroxide-induced apoptosis in rat myocardial cells

Purpose: To investigate the protective effect of the acetone extract of Rumex japonicas Houtt. (AER) on rat myocardial cells.Methods: R. japonicas was extracted with 75 % aqueous ethanol by reflux to afford total extract (TER). TER was suspended in water and then extracted with acetone to afford acetone fraction of R. japonicas (AER). High performance liquid chromatography (HPLC) combined with standard substances was carried out to analyze the major constituents of AER. Apoptosis in myocardial H9c2 cell line was induced by H2O2 (100 μmol/L). The cells were treated with AER (50, 100 and 200 μg/mL, and cell viability was evaluated by the 3-（4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, while oxidative stress level in H9c2 cells was evaluated by determining levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), creatinine kinase (CK), superoxide dismutase (SOD), and catalase (CAT). Furthermore, apoptotic proteins (caspase-3, Bax and Bcl-2) in H9c2 cells were analyzed by using western blot assay.Results: Results revealed that the main components of AER are aloe-emodin, rhein, emodin, chrysophanol and physcion. AER (50, 100 and 200 μg/mL) inhibited the cell viability reduction of the H9c2 cells induced by H2O2 (p < 0.05, p < 0.01, p < 0.01, respectively). AER (50, 100 and 200 μg/mL) decreased LDH and CK contents of H9c2 cells (p < 0.01). The levels of SOD (p<0.01) and CAT (p < 0.01) were increased by AER treatments (100 and 200 μg/mL); in addition, AER (50, 100 and 200 μg/mL) decreased MDA levels (p < 0.01). Besides, the present results also revealed that AER could down-regulate caspase-3 and Bax, but up-regulated Bcl-2.Conclusion: AER alleviates apoptosis induced by H2O2 in myocardial H9c2 cells via inhibition of oxidative stress and mitochondria-mediated apoptosis. This finding suggests that AER can potentially be developed for the treatment of myocardial apoptosis.Keywords: Rumex japonicas Houtt., Myocardial cells, Apoptosis, H9c2 cell, Oxidative stres

The influence of joining overseas service learning on college students\u27 service learning experience and whole person development

Service learning, involving college students in community service, has become a need for enhancing their learning in Taiwan. However, despite the increasing numbers of service-learning has been provided from Taiwan universities to the communities, there is limited research findings of what the influences of service-learning, especially in overseas or international service learning, on college students learning experience and their whole person development. To evaluate college students’ changes of joining overseas service learning, this study compared the scales of the experience of service learning, personal growth, interpersonal growth, intellectual growth, and responsibility of citizenship from 49 college students of Fu Jen Catholic University. The results of the study revealed that most of above -mentioned variables had positive and significant changes. To sum up, joining overseas service learning would deepen college students\u27 experience of service learning and facilitate them toward positive development

Effects of the overseas service learning experience on the college students\u27 mental adjustment

The study examined the effects of the service learning experience on undergraduate students’ mental adjustment in Taiwan. A total of 49 undergraduate students of Fu Jen Catholic University filled out questionnaires on the positive/negative experience of service learning, levels of life satisfaction and depressive levels before and after joining overseas service learning. Hierarchical regression analyses were conducted and the results revealed that the positive experience of service learning positively contributed to life satisfaction in pre-test and post-test of joining overseas service learning. Meanwhile, the results revealed the negative experience of service learning positively contributed to depression in pre-test of joining overseas service learning. This study implied that the acquiring positive experience of service learning could increase life satisfaction of college students. Furthermore, the change of negative experience of service learning might decrease the degree of depression of college students

College students\u27 changes of thinking styles, personality traits, and mental adjustment after joining overseas service learning

Service learning has become a very popular approach for enhancing whole personal development for students at Taiwan universities. However, there is little attention to the actual changes after joining service learning, especially in overseas service learning. To evaluate the changes of joining overseas service learning, this study compared the scales of thinking styles (including positive, negative thinking styles), personality traits (including hope, resilience, self-esteem), and mental adjustment (life satisfaction, depression) from 49 college students of Fu Jen Catholic University. The results of the study revealed that most of above-mentioned variables had positive and significant changes. In summary, college students joining overseas service learning had positive changes in thinking styles, personality traits, and mental adjustment

Assessment of the impact of intravenous antibiotics treatment on gut microbiota in patients: Clinical data from pre-and post-cardiac surgery

Background and aimsSurgical site infection is a common complication after surgery. Periprocedural antibiotics are necessary to prescribe for preventing or treating infections. The present study aimed to explore the effect of intravenous antibiotics on gut microbiota and menaquinone biosynthesis in patients, especially in elderly patients undergoing cardiac surgery.MethodsA total of 388 fecal samples were collected from 154 cardiac surgery patients. The V3–V4 hypervariable region of the bacterial 16S rRNA gene was amplified and sequenced on a MiSeq PE300. The gut microbiota diversity of samples was analyzed in terms of α- and β-diversity at the OTU level. The different groups were classified according to antibiotics in combinations and single antibiotics. PICRUSt2 was used for preliminary prediction of the gut microbiota function for menaquinone biosynthesis.ResultsThe intravenously administered antibiotics which are excreted via bile represents the main antibiotics that could disturb the gut microbiota’s composition in cardiac surgery patients, especially for elderly patients. The effect of antibiotics on gut microbiota is produced after antibiotics treatments over one week. The recovery of gut microbiota to the state of pre-antibiotics may require over two weeks of antibiotics withdrawal. Sex factor doesn’t represent as an influencer in gut microbiota composition. Long-term use of cefoperazone-sulbactam may affect coagulation function.ConclusionsThe composition of the gut microbiota had a significant change post-intravenous antibiotics treatment in cardiac surgery patients. The richness and diversity of gut microbiota are increased in elderly patients

Transiently impaired endothelial function during thyroid hormone withdrawal in differentiated thyroid cancer patients

PurposeEndothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy.MethodsWe recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the day before thyroxine withdrawal(P1), the day before 131I administration(P2) and 4-6 weeks after RAI therapy(P3). A high-resolution ultrasound named flow-mediated dilation (FMD) was used to measure endothelial function of the patients.ResultsWe analyzed the changes of FMD, thyroid function and lipids at three time points. FMD(P2) decreased significantly compared to FMD(P1) (P1vsP2, 8.05 ± 1.55vs 7.26 ± 1.50, p<0.001). There was no significant difference between FMD(P3) and FMD(P1) after restoring TSH (thyroid stimulating hormone) suppression therapy (P1 vs P3, 8.05 ± 1.55 vs 7.79 ± 1.38, p=0.146). Among all parameters, the change of low-density lipoprotein (ΔLDL) was the only factor correlated negatively with the change of FMD (ΔFMD) throughout the RAI therapy process (P1-2, r=-0.326, p=0.020; P2-3, r=-0.306, p=0.029).ConclusionEndothelial function was transiently impaired in DTC patients at short-term hypothyroidism state during the RAI therapy, and immediately returned to the initial state after restoring TSH suppression therapy

HuR cytoplasmic expression is associated with increased cyclin A expression and poor outcome with upper urinary tract urothelial carcinoma

BACKGROUND: HuR is an RNA-binding protein that post-transcriptionally modulates the expressions of various target genes implicated in carcinogenesis, such as CCNA2 encoding cyclin A. No prior study attempted to evaluate the significance of HuR expression in a large cohort with upper urinary tract urothelial carcinomas (UTUCs). METHODS: In total, 340 cases of primary localized UTUC without previous or concordant bladder carcinoma were selected. All of these patients received ureterectomy or radical nephroureterectomy with curative intents. Pathological slides were reviewed, and clinical findings were collected. Immunostaining for HuR and cyclin A was performed and evaluated by using H-score. The results of cytoplasmic HuR and nuclear cyclin A expressions were correlated with disease-specific survival (DSS), metastasis-free survival (MeFS), urinary bladder recurrence-free survival (UBRFS), and various clinicopathological factors. RESULTS: HuR cytoplasmic expression was significantly related to the pT status, lymph node metastasis, a higher histological grade, the pattern of invasion, vascular and perineurial invasion, and cyclin A expression (p = 0.005). Importantly, HuR cytoplasmic expression was strongly associated with a worse DSS (p < 0.0001), MeFS (p < 0.0001), and UBRFS (p = 0.0370) in the univariate analysis, and the first two results remained independently predictive of adverse outcomes (p = 0.038, relative risk [RR] = 1.996 for DSS; p = 0.027, RR = 1.880 for MeFS). Cyclin A nuclear expression was associated with a poor DSS (p = 0.0035) and MeFS (p = 0.0015) in the univariate analysis but was not prognosticatory in the multivariate analyses. High-risk patients (pT3 or pT4 with/without nodal metastasis) with high HuR cytoplasmic expression had better DSS if adjuvant chemotherapy was performed (p = 0.015). CONCLUSIONS: HuR cytoplasmic expression was correlated with adverse phenotypes and cyclin A overexpression and also independently predictive of worse DSS and MeFS, suggesting its roles in tumorigenesis or carcinogenesis and potentiality as a prognostic marker of UTUC. High HuR cytoplasmic expression might identify patients more likely to be beneficial for adjuvant chemotherapy