Design and evaluation of a remote synchronous gamified mathematics teaching activity that integrates multi-representational scaffolding and a mind tool for gamified learning.

Gamified learning is an instructional strategy that motivates students to learn, and the use of multiple representations assists learning by promoting students' thinking and advanced mathematical problem-solving skills. In particular, emergency distance learning caused by the COVID-19 pandemic may result in a lack of motivation and effectiveness in learning. This study designed an online gamified learning activity incorporating multi-representational scaffolding and compared the differences in the learning achievement and motivation for the gamified activity and general synchronous distance learning. In addition, for the group that conducted the gamified learning activity, we measured the participants' flow, anxiety, and emotion during the activity. A total of 36 high school students participated in the experiment. The results indicated that the gamified learning activity was not significantly effective in terms of enhancing learning achievement. In terms of learning motivation, a significant decrease in motivation was found for the group using general synchronous learning, while a significant increase in motivation was found for the group using synchronous gamified learning. This indicates that despite the negative impact of the pandemic on learning, gamified learning still enhances students' learning motivation. The results of flow, anxiety, and emotion showed that the participants had a positive and engaged experience. Participants provided feedback that the multi-representational scaffolding facilitates learning.

Analysis of status quo and influencing factors for health-promoting lifestyle in the rural populace with high risk of cardiovascular and cerebrovascular diseases.

OBJECTIVE: To explore the status quo and influencing factors for health-promoting lifestyle in the rural populace with high risk of cardiovascular and cerebrovascular diseases, and to provide reference for developing primary prevention strategies for cardiovascular and cerebrovascular diseases. METHOD: Questionnaire-based survey of 585 cases of high-risk cardiovascular and cerebrovascular population in 11 administrative villages in Fuling of Lishui city was conducted using the Health Promoting Lifestyle Profile-II (HPLP II), Perceived Social Support from Family Scale (PSS-Fa), General Health Questionnaire (GHQ-12), and other questionnaire tools. RESULTS: The total score of the health-promoting lifestyle in the rural populace with high risk of cardiovascular disease is 125.55 ± 20.50, which is at an average level, and the mean scores of each dimension in descending order are-nutrition, interpersonal support, self-actualization, stress management, health responsibility, and exercise. Monofactor analysis revealed that age, education level, marriage, monthly per capita household income, physical activity based on the International Physical Activity Questionnaire (IPAQ), family support function, carotid intima-media thickness, and blood pressure were influencing factors for the health-promoting lifestyle in the rural populace with high risk of cardiovascular and cerebrovascular diseases (P < 0.05). Multiple stepwise regression analysis showed that monthly per capita household income, family support function, physical activity based on the IPAQ, and education level were positively correlated with the level of the health-promoting lifestyle. CONCLUSION: The health-promoting lifestyle level of the rural populace with high risk of cardiovascular and cerebrovascular diseases needs to be improved. When assisting patients to improve their health-promoting lifestyle level, it is imperative to pay attention to improving patients' physical activity level, emphasizing the influence of the family environment on patients, and focusing on patients with economic difficulties and low education level.

The Combination of Chrysin and Cisplatin Induces Apoptosis in HepG2 through Down-regulation of cFLIP and Activity of Caspase.

AIM: The study aims to investigate the combined effects of chrysin and cisplatin on hepatoma(HepG2) cell lines in vivo and in vitro. OBJECTIVE: Studies have suggested that chrysin can enhance the sensitivity of tumor cells to apoptosis. Drug resistance in tumor cells reduced the effectiveness of chemotherapy drugs such as cisplatin. We investigated whether the combination of chrysin and cisplatin can induce more apoptosis than chrysin alone and cisplatin alone. METHODS: HepG2 cells were pretreated with chrysin for 2 h, followed by the addition of cisplatin for another 24 h. The morphologic changes were observed under inverted microscope and the cell viability was measured using the MTT test. The protein and cleavage of caspase-3,8,9, PARP, and cFLIP were determined by Western blotting. RESULTS: The cell viability of the HepG2 cell can be reduced by the combination of chrysin pretreatment for 2 h and cisplatin addition for 24 h; Caspase-3,8,9 and PARP were cleaved after 12 h treatment with chrysin and cisplatin; Pancaspase inhibitor, Z-VAD-fmk, could reverse the apoptosis induced by chrysin and cisplatin in HepG2 cells; cFLIP was down-regulated by the combination of chrysin and cisplatin, and could be reversed by Z-VAD-fmk; the xenografted HepG2 cells formed a tumor in one week; At the end of the experiment, there were significant differences in relative tumor volume (RTV) and relative tumor proliferation rate between the combined group and the control group, the chrysin group and the cisplatin group; Western blotting showed that the levels of PARP, cFLIP, and caspase-3 proteins in isolated tumor tissues also decreased under the combined action of chrysin and cisplatin. CONCLUSION: The combination of chrysin and cisplatin induces apoptosis of hepatic tumor in vivo and in vitro. It downregulates cFLIP and then activates caspase-8, which triggers caspase-mediated apoptosis of HepG2 cell.

Effect of doctor-patient news-induced moral judgments on pain empathy for doctors and patients in China.

Objective: Pain empathy's preferential nature tends to trigger prejudice and intergroup conflicts. Given the current degree of proliferation of doctor-patient conflict news in China, this study aims to determine whether readers of doctor-patient news-initiated moral judgments prefer pain empathy for doctors or patients. Materials and methods: This study utilized localized doctor-patient news with high or low moral performance (based on morality ratings of patients' behaviors) as moral-judgment-eliciting materials, and painful pictures as pain empathy-eliciting materials. The event-related potential (ERP) technique was utilized to assess moral judgment's effect on the cognitive empathy component and to investigate electroencephalogram signals' accuracy in classifying four brain response patterns when facing doctor or patient is experiencing or not experiencing pain. Results: Under low moral text material, participants exhibited smaller mean wave amplitude of positive 300 (P3) and late positive potential (LPP) to painful pictures than non-painful pictures when facing patients; under high moral text material, participants exhibited larger mean wave amplitude of P3 and LPP to painful pictures than non-painful pictures when facing doctors. Electroencephalogram (EEG) signals' classification accuracy was significant in 0-1,000 ms in both high and low moral judgments, but the classification accuracy was higher in low moral judgments in some cognitive empathy stages (0.51, 0.53-0.55, 0.66-0.79, and 0.88-1 s). Conclusion: Under low moral judgment, individuals pay less attention to the patient's (perpetrator's) pain; under high moral judgment, individuals empathize with the doctor (the person praised), showing that news-induced moral judgment can sway readers' empathy for different social groups. In cognitive empathy, individuals' brain representations are more discriminatory under low than high moral judgments when confronted with pain by doctors and patients, which provides insight into objectively recognizing group bias.

Effects of Ambidextrous Leadership on Employees' Work Behavior: The Mediating Role of Psychological Empowerment.

The complexity of today's organizational environment increasingly requires leaders to think in a dynamic and flexible way to resolve contradictory issues. This study explored and compared the effects of servant leadership and authoritarian leadership on employees' work behavior from the perspectives of ambidextrous leadership theory and social exchange theory, and further examined the mediating role of psychological empowerment. In this study, 315 employees from state-owned communication companies in Shandong and Zhejiang Provinces in China were selected as subjects, and path analysis was used to test the hypotheses. The results showed that servant leadership positively predicted organizational citizenship behavior and task performance. While authoritarian leadership negatively predicted organizational citizenship behavior and positively predicted task performance, psychological empowerment mediated the relationship between the two leadership styles and organizational citizenship behavior and task performance. Moreover, psychological empowerment and organizational citizenship behavior played a multiple mediating role between the two leadership styles and task performance. The theoretical implications of these findings for advancing the ambidextrous leadership theory in Chinese organizational contexts and practical approaches for corporate managers to effectively use ambidextrous leadership style were discussed.

Forrest Classification for Bleeding Peptic Ulcer: A New Look at the Old Endoscopic Classification.

The management of peptic ulcer bleeding is clinically challenging. For decades, the Forrest classification has been used for risk stratification for nonvariceal ulcer bleeding. The perception and interpretation of the Forrest classification vary among different endoscopists. The relationship between the bleeder and ulcer images and the different stages of the Forrest classification has not been studied yet. Endoscopic still images of 276 patients with peptic ulcer bleeding for the past 3 years were retrieved and reviewed. The intra-rater agreement and inter-rater agreement were compared. The obtained endoscopic images were manually drawn to delineate the extent of the ulcer and bleeding area. The areas of the region of interest were compared between the different stages of the Forrest classification. A total of 276 images were first classified by two experienced tutor endoscopists. The images were reviewed by six other endoscopists. A good intra-rater correlation was observed (0.92-0.98). A good inter-rater correlation was observed among the different levels of experience (0.639-0.859). The correlation was higher among tutor and junior endoscopists than among experienced endoscopists. Low-risk Forrest IIC and III lesions show distinct patterns compared to high-risk Forrest I, IIA, or IIB lesions. We found good agreement of the Forrest classification among different endoscopists in a single institution. This is the first study to quantitively analyze the obtained and explain the distinct patterns of bleeding ulcers from endoscopy images.

Current Status and Future Perspective of Artificial Intelligence in the Management of Peptic Ulcer Bleeding: A Review of Recent Literature.

With the decreasing incidence of peptic ulcer bleeding (PUB) over the past two decades, the clinician experience of managing patients with PUB has also declined, especially for young endoscopists. A patient with PUB management requires collaborative care involving the emergency department, gastroenterologist, radiologist, and surgeon, from initial assessment to hospital discharge. The application of artificial intelligence (AI) methods has remarkably improved people's lives. In particular, AI systems have shown great potential in many areas of gastroenterology to increase human performance. Colonoscopy polyp detection or diagnosis by an AI system was recently introduced for commercial use to improve endoscopist performance. Although PUB is a longstanding health problem, these newly introduced AI technologies may soon impact endoscopists' clinical practice by improving the quality of care for these patients. To update the current status of AI application in PUB, we reviewed recent relevant literature and provided future perspectives that are required to integrate such AI tools into real-world practice.

Reliability and validity of the Mandarin version of the Continuity Assessment Record and Evaluation for older people who are transferred between hospitals and nursing homes in China.

To date, assessment tools for older people are different between hospitals and nursing homes in China. The difference between assessment tools can lead to poor communication of information between hospitals and nursing homes, which causes discontinuity of care and adverse outcomes when older people are transferred between these different settings. Continuity Assessment Record and Evaluation (CARE) is a comprehensive geriatric assessment tool developed in the United States of America. This study aimed to evaluate the reliability and validity of the Mandarin Version of CARE for older people who are transferred between hospitals and nursing homes. Using a convenience sampling method, 120 older people in hospitals and 120 older people in nursing homes in Shanghai were selected to test the internal consistency, interrater reliability and criterion-related validity of CARE from May to November 2017. When used among hospital, 70.0% (7/10) of the subscales had a Cronbach's alpha coefficients of greater than 0.7, 94.3% (50/53) of the items had an intraclass correlation coefficient (ICC) of greater than 0.75. When used in nursing homes, 90.0% (9/10) of the subscales had a Cronbach's alpha coefficients of greater than 0.7, 94.3% (50/53) of the items had an ICC of greater than 0.75. For both settings, the correlation coefficients of the subscales with their corresponding instruments for criterion-related validity were all greater than 0.8 (p < .01). The Mandarin version of CARE exhibits good reliability and validity. It can be used as an assessment tool for transition between hospitals and nursing homes.

Reliability and validity of a questionnaire for job satisfaction with influenza vaccine recommendation of community diabetes management doctors / 预防医学

Objective@#To evaluate the reliability and validity of a questionnaire for job satisfaction with influenza vaccine recommendation of community diabetes management doctors.@*Methods@#Through the literature review,expert interviews and pilot survey,a questionnaire for job satisfaction with influenza vaccine recommendation of community diabetes management doctors was initially formed. Cronbach's α coefficient was used to evaluate the reliability of the questionnaire; correlation analysis,exploratory factor analysis（EFA）and confirmatory factor analysis（CFA）were used to evaluate the validity of the questionnaire. @*Results @#The questionnaire had 23 items, which were categorized into four dimensions: working environment,job itself,general satisfaction and occupational load. The Cronbach's α coefficient of working environment,job itself,general satisfaction, occupational load and the total questionnaire was 0.924,0.884,0.937,0.891 and 0.936,respectively. EFA showed that the characteristic roots of four dimensions were all more than one,and the cumulative variance proportion was 73.82%. The Pearson correlation coefficient between each item and the total questionnaire ranged from 0.339 to 0.818, and the correlation coefficient between each dimension and the total questionnaire ranged from 0.429 to 0.872（all P<0.05）. CFA showed that the variances of parameter estimation errors were all positive,and the standard errors ranged from 0.035 to 0.099,which were statistically significant（P<0.05）;the standardized parameters between each item and dimension ranged from 0.596 to 0.939; χ2/df was 4.627（P<0.05）, the comparative fit index was 0.827,the root mean square error of approximation was 0.076,which indicated the model fit. @*Conclusion@#The questionnaire has good reliability and validity,so it can be used to evaluate the satisfaction with influenza vaccine recommendation of community diabetes management doctors.

Combination of quercetin and cisplatin enhances apoptosis in OSCC cells by downregulating xIAP through the NF-κB pathway.

While cisplatin is a first-line chemotherapeutic drug commonly used to treat patients with oral squamous cell carcinoma (OSCC), the cisplatin-resistance poses a major challenge for its clinical application. Recent studies have shown that quercetin, a natural flavonoid found in various plants and foods possesses an anti-cancer effect. The following study examined the combined effect of quercetin and cisplatin on OSCC apoptosis in vitro and in vivo (using a mice tumor model). We found that quercetin promotes cisplatin-induced apoptosis in human OSCC (cell lines Tca-8113 and SCC-15) by down-regulating NF-κB. Pretreatment of cancer cells with quercetin inhibited the phosphorylation Akt and IKKß, and led to the suppression of NF-κB and anti-apoptotic protein xIAP. In addition, we observed that the pretreatment of cancer cells with quercetin improves extrinsic and intrinsic apoptosis by activating caspase-8 and caspase-9, respectively. Our in vivo data also indicated that the combination of quercetin and cisplatin may inhibit the xenograft growth in mice. To sum up, our results provide a new evidence for the application of quercetin and cisplatin in OSCC therapy.

Serum biomarker panels for the diagnosis of gastric cancer.

Gastric cancer is a leading cause of mortality due to neoplastic disease. Although early detection of gastric cancers can decrease the mortality rate, it remains a diagnostic challenge because of the lack of effective biomarkers. In this study, fifteen gastric cancer patients and ten healthy subjects were recruited to assess novel serum biomarkers for gastric cancer using antibody microarray technology. ELISA was utilized to validate the antibody array results. As a result, compared to the controls, eleven cytokines were found to be significantly increased in gastric cancer, including interferon gamma receptor 1 (IFNGR1), neurogenic locus notch homolog protein 3 (Notch-3), tumor necrosis factor receptor superfamily member 19L (TNFRSF19L), growth hormone receptor (GHR), signaling lymphocytic activation molecule family 8 (SLAMF8), folate receptor beta (FR-beta), integrin alpha 5, galectin-8, erythropoietin-producing hepatocellular A1 (EphA1), epiregulin, and fibroblast growth factor 12 (FGF-12) with P < 0.05. ELISA validation supported the results of the antibody array. More importantly, most of these eleven cytokines, including IFNGR1, TNFRSF19L, GHR, SLAMF8, FR-beta, and integrin alpha 5 were discovered to be elevated in gastric cancer serum samples for the first time in this study, suggesting that these proteins may serve as novel biomarkers for the early diagnosis and prognosis determination of gastric cancer.

Erianin protects against high glucose-induced oxidative injury in renal tubular epithelial cells.

Erianin is the major bibenzyl compound found in Dendrobium chrysotoxum Lindl. The current study was designed to investigate the protective effects of erianin on high glucose-induced injury in cultured renal tubular epithelial cells (NRK-52E cells) and determine the possible mechanisms for its effects. NRK-52E cells were pretreated with erianin (5, 10, 25 or 50 nmol/L) for 1 h followed by further exposure to high glucose (30 mmol/L, HG) for 48 h. Erianin concentration dependently enhanced cell viability followed by HG treatment in NRK-52E cells. HG induced reactive oxygen species (ROS) generation, malondialdehyde production, and glutathione deficiency were recovered in NRK-52E cells pretreated with erianin. HG triggered cell apoptosis via the loss of mitochondrial membrane potential, depletion of adenosine triphosphate, upregulation of caspases 9 and 3, enhancement of cytochrome c release, and subsequent interruption of the Bax/Bcl-2 balance. These detrimental effects were ameliorated by erianin. HG also induced activation of p53, JNK, p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) in NRK-52E cells, which were blocked by erianin. The results suggest that treatment NRK-52E cells with erianin halts HG-induced renal dysfunction through the suppression of the ROS/MAPK/NF-κB signaling pathways. Our findings provide novel therapeutic targets for diabetic nephropathy.

Gigantol has Protective Effects against High Glucose-Evoked Nephrotoxicity in Mouse Glomerulus Mesangial Cells by Suppressing ROS/MAPK/NF-κB Signaling Pathways.

Gigantol is a bibenzyl compound derived from several medicinal orchids. This biologically active compound has shown promising therapeutic potential against diabetic cataracts, but whether this compound exerts beneficial effects on the other diabetic microvascular complications remains unclear. This study was carried out to examine effects of gigantol on high glucose-induced renal cell injury in cultured mouse kidney mesangial cells (MES-13). MES-13 cells were pretreated with gigantol (1, 5, 10 or 20 µmol/L) for 1 h followed by further exposure to high (33.3 mmol/L) glucose for 48 h. Gigantol concentration dependently enhanced cell viability followed by high glucose treatment in MES-13 cells. High glucose induced reactive oxygen species (ROS) generation, malondialdehyde production and glutathione deficiency were recoved in MES-13 cells pretreated with gigantol. High glucose triggered cell apoptosis via the the loss of mitochondrial membrane potential, depletion of adenosine triphosphate, upregulation of caspases 9 and 3, enhancement of cytochrome c release, and subsequent interruption of the Bax/Bcl-2 balance. These detrimental effects were ameliorated by gigantol. High glucose also induced activation of JNK, p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) in MES-13 cells, which were blocked by gigantol. The results suggest that treatment MES-13 cells with gigantol halts high glucose-induced renal dysfunction through the suppression of the ROS/MAPK/NF-κB signaling pathways. Our data are of value to the understanding the mechanism for gigantol, and would benefit the study of drug development or food supplement for diabetes and nephropathy.

Web-Based Experience Sharing Platform on Medical Device Incidents for Clinical Engineers in Hospitals.

The aim of this study was to establish a web-based platform for exchanging medical device management and maintenance experiences to enhance the professional competency of clinical engineers (CEs), which ensures the quality of medical devices and increases patients' satisfaction with medical services. Medical devices play an essential role in diagnosis and disease management. CEs are responsible for providing functional medical devices that contribute worthwhile functions to a medical service to improve patients' health and safety. The purpose of the platform is to facilitate collection and sharing of medical device incidents experiences to improve CEs' capability. To provide useful and practical information for CEs, an event review committee, composed of experts with more than 20 years of clinical engineering experience who were recruited as reviewers, was established under the platform. Cases submitted to the platform were required to have comprehensive descriptions of the device and events. Each case was evaluated by at least two reviewers based on five evaluation indices: (1) severity, (2) breadth, (3) frequency, (4) insidiousness, and (5) correctness. After being reviewed, each final report was published on the platform to be shared with the event submitters and other members. The results show that 116 staffs from 32 different hospitals, registered to join this platform. From January 2015 to December 2016, 70 events were submitted with 56 reports. This study also assessed the platform's benefits for CEs. A total of 93 respondents completed a questionnaire survey: 93% of the CEs agreed that the information from the platform helped them do their job. The web-based platform has high value as an experience-sharing interface for medical devices. The CEs obtained extremely useful information from the platform for medical device management and their daily duties. This study provided an online training model with systematic methods to improve the quality and effectiveness of medical device management.

Optimal Energy Delivery, Rather than the Implementation of a Feeding Protocol, May Benefit Clinical Outcomes in Critically Ill Patients.

Malnutrition is common in intensive care units (ICU), and volume based feeding protocols have been proposed to increase nutrient delivery. However, the volume based approach compared to trophic feeding has not been proven entirely successful in critically ill patients. Our study aimed to compare the clinical outcomes both before and after the implementation of the feeding protocol, and to also evaluate the effects of total energy delivery on outcomes in these patients. We retrospectively collected all patient data, one year before and after the implementation of the volume-based feeding protocol, in the ICU at Taichung Veterans General Hospital. Daily actual energy intake from enteral nutritional support was recorded from the day of ICU admission until either the 7th day of ICU stay, or the day of discharge from the ICU. The energy achievement rate (%) was calculated as: (actual energy intake/estimated energy requirement) × 100%. Two-hundred fourteen patients were enrolled before the implementation of the volume-based feeding protocol (pre-FP group), while 198 patients were enrolled after the implementation of the volume-based feeding protocol (FP group). Although patients in the FP group had significantly higher actual energy intakes and achievement rates when compared with the patients in the pre-FP group, there was no significant difference in mortality rate between the two groups. Comparing survivors and non-survivors from both groups, an energy achievement rate of less than 65% was associated with an increased mortality rate after adjusting for potential confounders (odds ratio, 1.6, 95% confidence interval, 1.01-2.47). The implementation of the feeding protocol could improve energy intake for critically ill patients, however it had no beneficial effects on reducing the ICU mortality rate. Receiving at least 65% of their energy requirements is the main key point for improving clinical outcomes in patients.

Elucidation of the therapeutic role of mitochondrial biogenesis transducers NRF-1 in the regulation of renal fibrosis.

BACKGROUND: Mitochondrial dysfunction is a newly established risk factor for the development of renal fibrosis. Cell survival and injury repair is facilitated by mitochondrial biogenesis. Nuclear respiratory factor 1 (NRF-1) is a transcriptional regulation factor that plays a central role in the regulation of mitochondrial biogenesis. However, the transcription factor of this process in renal fibrosis is unknown. Thus, we hereby discussed the correlations of NRF-1 and renal interstitial fibrosis. MATERIALS AND METHODS: In vitro fibrosis model was established by treatment with transforming growth factor-ß1 (TGF-ß1) in NRK-49F (Normal Rat kidney fibroblast). We investigated the ROS production, mitochondrial biogenesis and fibrogenic marker (e.q. fibronectin) during the progression of renal fibrosis by kit and Western blotting assay. Here, we used that two distinct mechanisms regulate NRF-1 activation and degradation of NRF-1. NRF-1 was transfect by pcDNA-NRF-1 overexpression gene to evaluate the NRF-1 activity of the therapeutic effect in renal fibrosis. In addition, NRF-1 was silenced by shRNA-NRF-1 to evaluate the significance of NRF-1. ELISA was used to evaluate the secreted fibronectin. Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin, NRF-1). RESULTS: Under renal fibrosis conditions, TGF-ß1 (5ng/ml) increased ROS. Simultaneously, TGF-ß1-induced extracellular fibronectin by ELISA assay. In addition, TGF-ß1 decreased expression of mitochondrial biogenesis. This is the first time to demonstrate that expression of NRF-1 is significantly decreased in renal fibrosis. However, NRK49F was a transfection with pcDNA-NRF-1 (2µg/ml) expression vector dramatically reverse TGF-ß1-induced cellular fibrosis concomitantly with the suppression of fibronectin (both intracellular and extracellular fibronectin). More importantly, transfection with shRNA-NRF-1 (2µg/ml) significantly increased the expression of fibronectin of both intercellular and extracellular origins in NRK-49F cells. DISCUSSION: These finding suggest that NRF-1 plays a pivotal role on renal cellular fibrosis. Moreover, NRF-1 might act as a novel renal fibrosis antagonist by down-regulating fibrosis signaling in renal fibroblast cells.

Treatment with cytokine thymic stromal lymphopoietin short hairpin RNA substantially reduces TGF-ß1-induced interstitial cellular fibrosis.

Thymic stromal lymphopoietin (TSLP) has previously been linked to allergic inflammatory diseases, and tissue fibrosis and organ dysfunction may also arise from such inflammation. It remains unclear, however, whether TSLP plays any role in the occurrence of renal fibrosis, so this study investigated that possibility. An in vitro fibrosis model was established by treating normal rat kidney fibroblast (NRK-49F) cells with transforming growth factor-ß1 (TGF-ß1), after which the levels of various fibrogenic markers (e.g., fibronectin) and downstream fibrogenic signal proteins (e.g., smad 7) were investigated. Also, TSLP shRNA was used to silence the effects of TSLP, while an ELISA was conducted to evaluate the fibronectin secretions. The level of fibronectin in the NRK-49F cells was dose- and time-dependently increased by the administration of exogenous TSLP (P<0.05). TSLP also significantly increased the level of fibrosis signaling, in addition to inducing a marked decrease in the down-regulation of Smad7. Interestingly, the application of TSLP shRNA caused a stark reversal of the TGF-ß1-induced cellular fibrosis while simultaneously leading to the suppression of fibronectin and fibrogenic signal proteins. Taken together, these observations provide insights into how extracellular matrices develop and could thus lead to potential therapeutic interventions for the suppression of renal fibrosis.

Characterization of imidazoline receptors in blood vessels for the development of antihypertensive agents.

It has been indicated that activation of peripheral imidazoline I2-receptor (I-2R) may reduce the blood pressure in spontaneously hypertensive rats (SHRs). Also, guanidinium derivatives show the ability to activate imidazoline receptors. Thus, it is of special interest to characterize the I-2R using guanidinium derivatives in blood vessels for development of antihypertensive agent(s). Six guanidinium derivatives including agmatine, amiloride, aminoguanidine, allantoin, canavanine, and metformin were applied in this study. Western blot analysis was used for detecting the expression of imidazoline receptor in tissues of Wistar rats. The isometric tension of aortic rings isolated from male rats was also estimated. The expression of imidazoline receptor on rat aorta was identified. However, guanidinium derivatives for detection of aortic relaxation were not observed except agmatine and amiloride which induced a marked relaxation in isolated aortic rings precontracted with phenylephrine or KCl. Both relaxations induced by agmatine and amiloride were attenuated by glibenclamide at concentration enough to block ATP-sensitive potassium (KATP) channels. Meanwhile, only agmatine-induced relaxation was abolished by BU224, a selective antagonist of imidazoline I2-receptors. Taken together, we suggest that agmatine can induce vascular relaxation through activation of peripheral imidazoline I2-receptor to open KATP channels. Thus, agmatine-like compound has the potential to develop as a new therapeutic agent for hypertension in the future.

Antihypertensive action of allantoin in animals.

The agonists of imidazoline I-1 receptors (I-1R) are widely used to lower blood pressure. It has been indicated that guanidinium derivatives show an ability to activate imidazoline receptors. Also, allantoin has a chemical stricture similar to guanidinium derivatives. Thus, it is of special interest to characterize the effect of allantoin on I-1R. In conscious male spontaneous hypertensive rats (SHRs), mean blood pressure (MBP) was recorded using the tail-cuff method. Furthermore, the hemodynamic analyses in catheterized rats were applied to measure the actions of allantoin in vivo. Allantoin decreased blood pressures in SHRs at 30 minutes, as the most effective time. Also, this antihypertensive action was shown in a dose-dependent manner from SHRs treated with allantoin. Moreover, in anesthetized rats, allantoin inhibited cardiac contractility and heart rate as showing in hemodynamic dP/dt max significantly. Also, the peripheral blood flow was markedly increased by allantoin. Both actions were diminished by efaroxan at the dose sufficient to block I-1R. Thus, we suggest that allantoin, as I-1R agonist, has the potential to develop as a new therapeutic agent for hypertension in the future.

The effects of diosgenin in the regulation of renal proximal tubular fibrosis.

Fibrosis is the important pathway for end-stage renal failure. Glucose has been demonstrated to be the most important fibrogenesis-inducing agent according to previous studies. Despite diosgenin has been demonstrated to be anti-inflammatory, the possible role in fibrosis regulation of diosgenin remain to be investigated. In this study, renal proximal tubular epithelial cells (designated as HK-2) were treated with high concentration of glucose (HG, 27.5mM) to determine whether diosgenin (0.1, 1 and 10 µM) has the effects to regulate renal cellular fibrosis. We found that 10 µM of diosgenin exert optimal inhibitory effects on high glucose-induced fibronectin expression in HK-2 cells. In addition, diosgenin markedly inhibited HG-induced increase in α-smooth muscle actin (α-SMA) and HG-induced decrease in E-cadherin. In addition, diosgenin antagonizes high glucose-induced epithelial-to-mesenchymal transition (EMT) signals partly by enhancing the catabolism of Snail in renal cells. Collectively, these data suggest that diosgenin has the potential to inhibit high glucose-induced renal tubular fibrosis possibly through EMT pathway.