Search

Background and Study Aim: Current capsule endoscopy procedures are ineffective for upper gastrointestinal (GI) tract examination because they do not allow for operator-controlled navigation of the capsule. External controllability of a capsule endoscope with an applied magnetic field is a possible solution to this problem. We developed a novel magnetic-assisted capsule endoscope (MACE) system to visualize the entire upper GI tract. The present study evaluated the safety and feasibility of the MACE system for the examination of the upper GI tract, including the esophagus, stomach, and duodenum.Methods: The present open clinical study enrolled ten healthy volunteers. All participants swallowed a MACE, and an external magnetic field navigator was used for magnetic capsule manipulation in the upper GI tract. We assessed the maneuverability of the magnetic capsule and completeness of the MACE examination as well as the safety and tolerability of the procedure.Results: The present study enrolled ten healthy volunteers with a mean age and body mass index of 47.7 years and 25.6 kg/m2, respectively. One volunteer withdrew because of difficulty in swallowing the capsule. In total, nine volunteers underwent the MACE examination. The average examination time was 27.1 min. The maneuverability of the capsule was assessed as good and fair in 55.6 and 44.4% of the participants, respectively. The overall completeness of the examination in the esophagus, stomach, and duodenum was 100, 85.2, and 86.1%, respectively. No severe adverse events occurred during this study. All participants exhibited satisfactory tolerance of the MACE examination.Conclusion: The MACE system has satisfactory maneuverability and visualization completeness with excellent acceptance and tolerance. [ABSTRACT FROM AUTHOR]

Asthma and chronic obstructive pulmonary disease (COPD) are common chronic lung inflammatory diseases. Thrombin and interleukin (IL)-8/C-X-C chemokine ligand 8 (CXCL8) play critical roles in lung inflammation. Our previous study showed that c-Src-dependent IκB kinase (IKK)/IκBα/nuclear factor (NF)-κB and mitogen-activated protein kinase kinase kinase 1 (MEKK1)/extracellular signal-regulated kinase (ERK)/ribosomal S6 protein kinase (RSK)-dependent CAAT/enhancer-binding protein β (C/EBPβ) activation are involved in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells. In this study, we aimed to investigate the roles of p300 and C/EBPβ-reliant IKKβ expression in thrombin-induced IL-8/CXCL8 expression. Thrombin-induced increases in IL-8/CXCL8-luciferase activity and IL-8/CXCL8 release were inhibited by p300 small interfering (siRNA). Thrombin-caused histone H3 acetylation was attenuated by p300 siRNA. Stimulation of cells with thrombin for 12 h resulted in increases in IKKβ expression and phosphorylation in human lung epithelial cells. However, thrombin did not affect p65 expression. Moreover, 12 h of thrombin stimulation produced increases in IKKβ expression and phosphorylation, and IκBα phosphorylation, which were inhibited by C/EBPβ siRNA. Finally, treatment of cells with thrombin caused increases in p300 and C/EBPβ complex formation, p65 and C/EBPβ complex formation, and recruitment of p300, p65, and C/EBPβ to the IL-8/CXCL8 promoter. These results imply that p300-dependent histone H3 acetylation and C/EBPβ-regulated IKKβ expression contribute to thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells. Results of this study will help clarify C/EBPβ signaling pathways involved in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells. [ABSTRACT FROM AUTHOR]

Colon cancer is the third most common malignancy worldwide. Recently, some interesting associations between ghrelin and cancer were reported, and it may participate in colon cancer development. In the present report, we explored the role of the growth hormone secretagogue receptor (GHS-R), Ras, phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR) pathways in the ghrelin-induced proliferation of human colon cancer cells. Ghrelin-caused HT-29 proliferation was reduced by [D-Lys3]-GHRP-6 (a GHS-R inhibitor). We also found that a dominant negative mutant of Ras (Ras DN), a PI3K inhibitor (LY 294002), an Akt DN, and an mTOR inhibitor (rapamycin) attenuated ghrelin-caused colon cancer cell proliferation. We found that ghrelin induced time-dependent increases in Ras activity. Moreover, ghrelin-mediated Akt Ser473 phosphorylation was attenuated by a Ras DN and LY 294002. Furthermore, a Ras DN, LY 294002, and an Akt DN all inhibited ghrelin-caused mTOR Ser2448 phosphorylation. These results indicate that the Ras/PI3K/Akt/mTOR cascade plays a critical role in ghrelin-induced colon cancer cell proliferation. [ABSTRACT FROM AUTHOR]

Previous report showed that epidermal growth factor (EGF) promotes tumor progression. Several studies demonstrated that growth factors can induce heme oxygenase (HO)-1 expression, protect against cellular injury and cancer cell proliferation. In this study, we investigated the involvement of the c-Src, NADPH oxidase, reactive oxygen species (ROS), PI3K/Akt, and NF-κB signaling pathways in EGF-induced HO-1 expression in human HT-29 colon cancer cells. Treatment of HT-29 cells with EGF caused HO-1 to be expressed in concentration- and time-dependent manners. Treatment of HT-29 cells with AG1478 (an EGF receptor (EGFR) inhibitor), small interfering RNA of EGFR (EGFR siRNA), a dominant negative mutant of c-Src (c-Src DN), DPI (an NADPH oxidase inhibitor), glutathione (an ROS inhibitor), LY294002 (a PI3K inhibitor), and an Akt DN inhibited EGF-induced HO-1 expression. Stimulation of cells with EGF caused an increase in c-Src phosphorylation at Tyr406 in a time-dependent manner. Treatment of HT-29 cells with EGF induced an increase in p47phox translocation from the cytosol to membranes. The EGF-induced ROS production was inhibited by DPI. Stimulation of cells with EGF resulted in an increase in Akt phosphorylation at Ser473, which was inhibited by c-Src DN, DPI, and LY 294002. Moreover, treatment of HT-29 cells with a dominant negative mutant of IκB (IκBαM) inhibited EGF-induced HO-1 expression. Stimulation of cells with EGF induced p65 translocation from the cytosol to nuclei. Treatment of HT-29 cells with EGF induced an increase in κB-luciferase activity, which was inhibited by a c-Src DN, LY 294002, and an Akt DN. Furthermore, EGF-induced colon cancer cell proliferation was inhibited by Sn(IV)protoporphyrin-IX (snPP, an HO-1 inhibitor). Taken together, these results suggest that the c-Src, NADPH oxidase, PI3K, and Akt signaling pathways play important roles in EGF-induced NF-κB activation and HO-1 expression in HT-29 cells. Moreover, overexpression of HO-1 mediates EGF-induced colon cancer cell proliferation. [ABSTRACT FROM AUTHOR]

This paper presents a novel solution of a hand-held external controller to a miniaturized capsule endoscope in the gastrointestinal (GI) tract. Traditional capsule endoscopes move passively by peristaltic wave generated in the GI tract and the gravity, which makes it impossible for endoscopists to manipulate the capsule endoscope to the diagnostic disease areas. In this study, the main objective is to present an endoscopic capsule and a magnetic field navigator (MFN) that allows endoscopists to remotely control the locomotion and viewing angle of an endoscopic capsule. The attractive merits of this study are that the maneuvering of the endoscopic capsule can be achieved by the external MFN with effectiveness, low cost, and operation safety, both from a theoretical and an experimental point of view. In order to study the magnetic interactions between the endoscopic capsule and the external MFN, a magnetic-analysis model is established for computer-based finite-element simulations. In addition, experiments are conducted to show the control effectiveness of the MFN to the endoscopic capsule. Finally, several prototype endoscopic capsules and a prototype MFN are fabricated, and their actual capabilities are experimentally assessed via in vitro and ex vivo tests using a stomach model and a resected porcine stomach, respectively. Both in vitro and ex vivo test results demonstrate great potential and practicability of achieving high-precision rotation and controllable movement of the capsule using the developed MFN. [ABSTRACT FROM PUBLISHER]

Acrokeratosis paraneoplastica is a rare disease and is uncommon even in patients with upper aerodigestive tract cancer. We report a 63-year-old man with a 1-month history of numerous pruritic lesions and vesicles on both feet. Although he had received local therapy, progressive dense scale formation involving both palms and both soles was found. Colonoscopy was performed because of hematochezia, and it revealed an early colon cancer. After the resection of the cancer, the skin lesions began to fall off dramatically. To the best of our knowledge, there is no report of acrokeratosis paraneoplastica associated with colon cancer in the literature. This is the first case report of acrokeratosis paraneoplastica associated with early colon cancer. [ABSTRACT FROM AUTHOR]

We developed a magnetic-assisted capsule colonoscope system with integration of computer vision-based object detection and an alignment control scheme. Two convolutional neural network models A and B for lumen identification were trained on an endoscopic dataset of 9080 images. In the lumen alignment experiment, models C and D used a simulated dataset of 8414 images. The models were evaluated using validation indexes for recall (R), precision (P), mean average precision (mAP), and F1 score. Predictive performance was evaluated with the area under the P-R curve. Adjustments of pitch and yaw angles and alignment control time were analyzed in the alignment experiment. Model D had the best predictive performance. Its R, P, mAP, and F1 score were 0.964, 0.961, 0.961, and 0.963, respectively, when the area of overlap/area of union was at 0.3. In the lumen alignment experiment, the mean degrees of adjustment for yaw and pitch in 160 trials were 21.70° and 13.78°, respectively. Mean alignment control time was 0.902 s. Finally, we compared the cecal intubation time between semi-automated and manual navigation in 20 trials. The average cecal intubation time of manual navigation and semi-automated navigation were 9 min 28.41 s and 7 min 23.61 s, respectively. The automatic lumen detection model, which was trained using a deep learning algorithm, demonstrated high performance in each validation index. [ABSTRACT FROM AUTHOR]

Aims and objectives. This study aimed to explore the correlation between fatigue and physical activity in patients with liver cirrhosis. Background. Many patients with liver cirrhosis perceive lower physical functioning and more fatigue than non-cirrhotic individuals. To date, however, few studies have examined the relationship between fatigue and physical activity in this patient population. Design. This study used a correlation design. Participants were patients with liver cirrhosis recruited from the gastroenterology clinic of a teaching medical centre in Taiwan. Methods. Data were collected using a structured questionnaire, consisting of a fatigue scale and a seven-day Physical Activity Recall scale. spss version 13.0 software was used to analyse the data through statistical methods, including one-way analysis of variance, independent t-test and Pearson's correlations. Results. Patients participating in this study suffered from moderate-to-severe fatigue, and their engagement in physical activity of moderate or higher intensity was decreased. On average, fatigue had a moderate level of influence on physical activity. A significant negative correlation was found between the fatigue level and average seven-day physical activity level. Conclusions. Patients with liver cirrhosis can experience severe fatigue, which may reduce their level of physical activity. Relevance to clinical practice. Early evaluation of the fatigue level and physical activity constraints in patients with liver cirrhosis should be conducted in the clinic or community. Individualised instructions for patient's physical activity should be provided. [ABSTRACT FROM AUTHOR]

This paper presents an autonomous navigation system for cost-effective magnetic-assisted colonoscopy, employing force-based sensors, an actuator, a proportional–integrator controller and a real-time heuristic searching method. The force sensing system uses load cells installed between the robotic arm and external permanent magnets to derive attractive force data as the basis for real-time surgical safety monitoring and tracking information to navigate the disposable magnetic colonoscope. The average tracking accuracy on magnetic field navigator (MFN) platform in x-axis and y-axis are 1.14 ± 0.59 mm and 1.61 ± 0.45 mm, respectively, presented in mean error ± standard deviation. The average detectable radius of the tracking system is 15 cm. Three simulations of path planning algorithms are presented and the learning real-time A* (LRTA*) algorithm with our proposed directional heuristic evaluation design has the best performance. It takes 75 steps to complete the traveling in unknown synthetic colon map. By integrating the force-based sensing technology and LRTA* path planning algorithm, the average time required to complete autonomous navigation of a highly realistic colonoscopy training model on the MFN platform is 15 min 38 s and the intubation rate is 83.33%. All autonomous navigation experiments are completed without intervention by the operator. [ABSTRACT FROM AUTHOR]

Abstract Background and Aims: The existence of gastric metaplasia (GM) of the duodenal mucosa has been considered to be highly related to the recurrence of duodenal ulcers (DU). The aims of this study are to evaluate the usefulness of methylene blue staining in the detection of GM, and to clarify the relationship between GM and the deformity of the duodenal bulb. Methods: Fifteen patients with healed DU and four patients with symptoms of dyspepsia without evidence of ulcers were enrolled into this endoscopic study. During each endoscopy, methylene blue was sprayed evenly on the duodenal bulb, and biopsies were taken from blue-stained and unstained areas. The existence and extent of GM were assessed histologically and grossly. The correlation between duodenal bulb deformity and the extent of GM was also studied. Results: The mean score of methylene blue non-staining (MBNS) was 0, 1.30 ± 0.15, and 3.00 ± 0.00 in group A (non-ulcer patients), group B (patients with healed DU and with normal-shaped bulb) and C (patients with healed DU and with deformed duodenal bulb), respectively; showing significant differences among the groups (P < 0.05 in each). Both the existence and the grading of GM were higher in unstained specimens than in blue-stained specimens (100 vs 16.6%, P < 0.0001 and 3.62 ± 0.09 vs 0.19 ± 0.06, P < 0.001, respectively). Conclusions: Methylene blue non-staining can be applied to investigate the existence and extent of GM in the duodenal bulb accurately. The incidence of GM in the duodenal bulb was higher in patients with healed ulcers than in non-ulcer patients. Patients with deformed duodenal bulbs have a higher extent of GM than those without deformed duodenal bulbs. [ABSTRACT FROM AUTHOR]

In this article, we propose a method for locating a magnetic capsule endoscope, which is utilized to observe the gastrointestinal tract, especially for colon. Recent studies mainly focus on either single-magnet positioning or multiple magnets positioning with similar scale in magnetic parameters, whereas these methods cannot be directly applied to the proposed magnetic-assisted capsule endoscope system, in which two magnets with big differences in magnetic parameters are used. An algorithm based on the Levenberg–Marquardt algorithm and a Hall sensor array is presented to solve this problem. Three different experiments have been carried out to validate the feasibility and effectiveness of the proposed method for the magnetic capsule positioning and orientation. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading cause of morbidity and mortality in patients with diabetes mellitus (DM), and patients with DM frequently develop diabetic cardiomyopathy. Currently, effective treatments for diabetic cardiomyopathy are limited. Vitamin D exerts pleiotropic effects on the cardiovascular system and is associated with DM. The purpose of this review was to evaluate published research on vitamin D in diabetic cardiomyopathy by searching PubMed databases. Herein, we reviewed vitamin D metabolism; evaluated the molecular, cellular, and neuroendocrine effects in native and bioactive vitamin D; and evaluated the role of vitamin D in treating cardiovascular disease and DM. Some evidence suggests that vitamin D may improve cardiovascular outcomes in diabetes through anti-inflammatory, antioxidative, antihypertrophic, antifibrotic, and antiatherosclerotic activities and by regulating advanced glycation end-product signaling, the renin-angiotensin system, and cardiac metabolism. This clinical and laboratory evidence suggests that vitamin D may be a potential agent in treating diabetic cardiomyopathy. However, using vitamin D entails possible adverse risks of hypercalcemia, hyperphosphatemia, and vascular calcifications. Therefore, future studies should be conducted that clarify the potential benefits of vitamin D through large-scale randomized clinical trials in well-defined groups of diabetic patients. [ABSTRACT FROM AUTHOR]

The Oriental Fruit Fly (OFF), Bactrocera dorsalis (Hendel), is one of most devastating insect pests that have periodically caused serious damage to fruit farms in Taiwan and many countries in the world. In the past, many studies reported that the population dynamics of OFF was partially correlated to the weather and the historical population development of OFF in the field. By making the best use of modern info-communication technologies (ICTs), long-term pest population data and microclimate variables measured with uniquely fine spatiotemporal resolution are now available to reveal the population dynamics of OFF. An analysis of data over three years using the Vector Auto-Regressive and Moving-Average model with eXogenous variables (VARMAX) was proposed to unravel the regulatory mechanism between the population dynamics of OFF and microclimate factors. In addition, the proposed model provides a 7-day forecast for population dynamics of OFF. The accuracy of 7-day risk level forecasting yielded by the proposed model ranges from 0.87 to 0.97, and the average root-mean squared errors of forecasting the population dynamics fall in the interval between 0.31 and 4.95 per day per farm. The proposed forecasting model can allow authorities to gain a better understanding of the dynamics of OFF and anticipate pest-related problems, so they can make preemptive and effective pest management decisions before the real problems occur. [ABSTRACT FROM AUTHOR]

Background: Colonoscopy is considered the most effective method for diagnosing colorectal diseases, but its application is sometimes limited due to invasiveness, patient intolerance, and the need for sedation. Objective: The aim of this study was to improve the problem of loop formation and shorten the cecal intubation time of colonoscopy by using a magnetic control system (MCS). Methods: Two experienced gastroenterologists, three trainees, and a novice repeated colonoscopy without or with MCS on three colonoscopy training model simulator cases. These cases were divided into introductory (case 2) and challenging levels (cases 4 and 5). The cecal intubation times were recorded. Results: For all cases, the average cecal intubation times for the experienced gastroenterologists with MCS were significantly shorter than without MCS (case 2: 52.45 vs. 27.65 s, p < 0.001; case 4: 166.7 vs. 120.55 s, p < 0.01; case 5: 130.35 vs. 100.2 s, p < 0.05). Those of the trainees also revealed significantly shorter times with MCS (case 2: 67.27 vs. 51 s, p < 0.01; case 4: 253.27 vs. 170.97 s, p < 0.001; case 5: 144.1 vs. 85.57 s, p < 0.001). Conclusion: Conducting colonoscopy with MCS is safe and smooth, and shortens the cecal intubation time by navigating the forepart of the colonoscope. In addition, all diagnostic and therapeutic benefits of conventional colonoscopy are retained. [ABSTRACT FROM AUTHOR]

Abstract: Background: Receptor for advanced glycation end products (RAGE) signaling pathway plays a vital role in diabetic cardiovascular complications. Calcitriol has been shown to exert various beneficial cardiovascular effects. The purpose of this study is to determine whether calcitriol can modulate RAGE expression, and study the potential mechanisms in diabetic hearts. Methods: Streptozotocin (65mg/kg, intraperitoneal injection once) induced diabetic rats were treated with or without subcutaneous injections of calcitriol at a dose of 150ng/kg/day for 4weeks. Western blot was used to evaluate protein expressions of myocardial RAGE, TNF-α, p65 subunit of NF-κB (p65), α subunit of inhibitor of κB (IκBα), subunits of NADPH oxidase (NOX4 and p22phox), angiotensin II type 1 receptor (AT1R), TGF-β1, TGF-β receptor I, total and phosphorylated SMAD2/3 and ERK, matrix metalloproteinases 2 (MMP2), tissue inhibitors of metalloproteinases 2 (TIMP2) and procollagen I. Results: As compared to control, diabetic rats had increased expressions of cardiac RAGE, TNF-α, p22phox, AT1R, and TGF-β1, which were significantly attenuated in the diabetic rats treated with calcitriol. Calcitriol-treated diabetic hearts also had lesser expressions of p-SMAD2/3 and p-ERK signaling than those of diabetic hearts. Moreover, diabetic hearts had increased expressions of MMP2 and procollagen I and decreased TIMP2. However, calcitriol reverted the diabetic effects in procollagen I but not in MMP2 or TIMP2. Conclusions: Calcitriol decreased diabetic effects on RAGE and fibrosis, which may be caused by its modulation on AT1R and the anti-inflammatory and antioxidative potentials. Therefore, calcitriol may attenuate diabetic cardiomyopathy. [Copyright &y& Elsevier]

Background: Histone deacetylases (HDACs), important epigenetic regulatory enzymes, can reduce cardiac hypertrophy and cardiac fibrosis. However, the mechanisms underlying the antifibrotic activity of HDAC inhibitors remain unclear. The purposes of this study were to evaluate the effects of an HDAC inhibitor on systolic heart failure (HF) and investigate the potential mechanisms. Methods: Echocardiographic, histologic, atrial natriuretic peptide (ANP), and Western blot measurements were performed in HF rats (isoproterenol 100mg/kg, subcutaneous injection) with and without orally administered (100mg/kg for 7 consecutive days) MPT0E014 (a novel HDAC inhibitor). Western blot, migration and proliferation assays were carried out on primary isolated cardiac fibroblasts with and without MPT0E014 (0.1 and 1μM) for 24h. Results: MPT0E014-treated HF rats (n=6) had better fraction shortening (48±2 vs. 33±4%, p =0.006) and smaller left ventricular end diastolic diameter (4.6±0.2 vs. 5.6±0.3mm, p =0.031) and systolic diameter (2.4±0.2 vs. 3.9±0.3mm, p =0.006) than HF (n=7) rats. MPT0E014-treated HF rats had lower ANP, cardiac fibrosis, and angiotensin II type I receptor (AT1R), transforming growth factor (TGF)-β, and CaMKIIδ protein levels compared to HF rats. MPT0E014 (at 1μM, but not 0.1μM) decreased the migration and proliferation of cardiac fibroblasts. MPT0E014 (0.1 and 1μM) decreased expression of the AT1R and TGF-β. Conclusions: MPT0E014 improved cardiac contractility and attenuated structural remodeling in isoproterenol-induced dilated cardiomyopathy. The direct antifibrotic activity may have contributed to these beneficial effects. [ABSTRACT FROM AUTHOR]

Heart failure ( HF) can increase atrial fibrillation and induce cardiac hypermethylation. The homeobox gene Pitx2c plays important roles in the genesis of atrial fibrillation and the promoter region of Pitx2c contains cytosine-phosphate-guanine islands. Therefore, epigenetic modification by hypermethylation may reduce Pitx2c expression in atrial myocytes. The aim of the present study were to evaluate whether HF can modulate DNA methylation of Pitx2c and the potential mechanisms involved., We used real-time polymerase chain reaction, immunoblotting and pyrosequencing to investigate RNA and protein expression, as well as the methylation of Pitx2c, in isoproterenol-induced HF, healthy rat left atria and in HL-1 cells with and without (control) exposure to angiotensin (Ang) II (0.1 and 1 μmol/L) or isoproterenol (1 or 10 μmol/L) for 24 h., The HF atrium exhibited increased Pitx2c promoter methylation with increased DNA methyltransferase ( DNMT) 1 and decreased Pitx2c protein levels compared with the normal atrium. Angiotensin II (0.1 and 1 μmol/L), increased Pitx2c promoter methylation in HL-1 cells with increased DNMT1 and decreased Pitx2c and Kir2.1 protein levels compared with control cells. These effects were attenuated by the methylation inhibitor 5-aza-2′-deoxycytidine (0.1 μmol/L) and by the Ang II receptor blocker losartan (10 μmol/L). However, isoproterenol (1 and 10 μmol/L) did not change the expression of the Pitx2c, DNMT1 and Kir2.1 proteins., In conclusion, HF induces Pitx2c promoter hypermethylation and Ang II may contribute to the hypermethylation in HF. [ABSTRACT FROM AUTHOR]

Stroke is one of the major causes of morbidity and mortality in recent. Oxygen free radicals produced during cerebral infarction increases the damage to neurons. Superoxide dismutase (SOD) is the endogenous antioxidant enzyme that can effectively scavenge superoxide radicals. Catechin is a hydrophilic antioxidant usually existed in tea, fruits and vegetables. In the cultured rat brain astrocytes (RBA), the activity of SOD (both Cu, Zn-SOD and Mn-SOD subtypes) was markedly increased by incubation with catechin at low concentration (0.1 μM) for 2 days (short-term) and 7 days (long-term). This stimulatory effect of catechin was not related to the incubating concentration. Similar changes were also observed in the gene expression of SOD in RBA. The increase in quantity of SOD-messenger RNA was remarkable and seemed to be more obvious than the other antioxidants such as vitamin E. This result shows that catechin is an effective antioxidant to increase the activity of SOD in RBA which would be beneficial to neurons subjected to oxygen free radical damage. [Copyright &y& Elsevier]