BSA-bounded p-cresyl sulfate potentiates the malignancy of bladder carcinoma by triggering cell migration and EMT through the ROS/Src/FAK signaling pathway.

Para-cresyl sulfate (P-CS), a major uremic toxin derived from the metabolites of tyrosine and phenylalanine through liver, existed in the blood of patients with chronic kidney disease (CKD). CKD increases the malignancy in bladder cancers; however, effects of P-CS on bladder cancers are not fully understood. P-CS is conjugated with BSA physiologically, and this study aims to investigate the effects and possible underlying mechanisms of BSA-bounded P-CS on human bladder cancer cells. With P-CS treatment, the intracellular ROS increased in bladder cancer cells. ROS then triggered epithelial-mesenchymal transition (EMT), stress fiber redistribution, and cell migration. With specific inhibitors, the key signals regulating P-CS-treated migration are Src and FAK. This study provided a clinical clue that patients with higher serum P-CS have a higher risk of malignant urothelial carcinomas, and a regulatory pathway of how P-CS regulates bladder cancer migration.

Andrographolide induces apoptosis of C6 glioma cells via the ERK-p53-caspase 7-PARP pathway.

BACKGROUND: Glioma is the most malignant tumor of the central nervous system. Efforts on the development of new chemotherapy are mandatory. Andrographolide (AND), a diterpenoid lactone isolated from the Andrographis paniculata, has been shown to have antitumor activities in several types of cancer cells. Whether AND can exert its antitumor activity in glioblastoma cells remains unknown. This study examined the anticancer effects of AND, both in vitro and in vivo. METHODS: Cell apoptosis was assayed by flow cytometry and nuclear staining. The signaling pathway for AND was determined by western blotting. The effects of AND on tumor growth was evaluated in a mouse model. RESULTS AND CONCLUSION: In vitro, with application of specific inhibitors and siRNA, AND-induced apoptosis was proven through ROS-ERK-P53-caspase 7-PARP signaling pathway. In vivo, AND significantly retarded tumor growth and caused regression of well-formed tumors in vivo. Furthermore, AND did not induce apoptosis or activate ERK and p53 in primary cultured astrocyte cells, and it may serve as a potential therapeutic candidate for the treatment of glioma.

PKCɛ mediates serine phosphorylation of connexin43 induced by lysophosphatidylcholine in neonatal rat cardiomyocytes.

Lysophosphatidylcholine (LPC) is a potent pro-arrhythmic derivative of the membrane phosphotidylcholine, which is accumulated in heart tissues during cardiac ischemia. However, the cellular mechanism underlying LPC-induced cardiomyocyte damage remains to be elucidated. This study focuses on the effects of LPC on cardiomyocyte gap junction. At 30µM, LPC decreased the spontaneous contraction rates of cardiomyocytes, and caused arrhythmic contraction without affecting cell viability. Connexin43 (Cx43) was seen as large plaques at cell junctions in control cells, whereas upon LPC treatment, the intensity of Cx43 staining was decreased in a concentration-sensitive manner and Cx43 staining appeared as tiny dots at cell junctions with a corresponding increase in cytoplasmic punctate staining. This distributional change of Cx43 was accompanied by an impairment of the gap junction intercellular communication (GJIC). Further, LPC treatment induced protein kinase C (PKC) activation, and PKC-dependent Cx43 phosphorylation at serine (Ser) 368. Pre-treatment with a specific PKCɛ inhibitor, eV1-2, prevented the LPC-induced Cx43 phosphorylation at Ser368 and the loss of Cx43 from gap junctions, both of which may disturb GJIC functions. Furthermore, siRNA knockdown of PKCɛ in H9c2 cells prevented LPC-induced serine phosphorylation of Cx43, confirming the role of PKCɛ in Cx43 serine phosphorylation. Double labeling immunofluorescence showed that LPC increased the colocalization of Cx43 with ubiquitin, and pretreatment with MG132 effectively prevented LPC-induced gap junction disassembly. LPC increased the ubiquitination of Cx43, which was blocked by eV1-2 pretreatment, suggesting that LPC accelerated the intracellular degradation of Cx43 via the ubiquitin-proteasomal pathway. It can be concluded that LPC destroyed the structure and function of gap junctions via PKCɛ-mediated serine phosphorylation of Cx43. PKCɛ inhibitors might therefore be effective in prevention of LPC-related diseases.

P-cresol induces disruption of cardiomyocyte adherens junctions.

Higher serum levels of p-cresol in chronic kidney disease populations have been associated with increased cardiovascular mortality. However, studies on how p-cresol affects intercellular junctions between cardiomyocytes were limited. This study investigated the effect of p-cresol on adherens junction (AJ) of neonatal cultured cardiomyocytes and its underlying mechanism. A loss of N-cadherin and p120-catenin (p120ctn) immunostaining from cell-cell contact sites was noted by p-cresol treatment. In addition, p-cresol disrupted AJs by inducing formation of intercellular gaps. Our previous study has revealed that p-cresol increased intracellular calcium levels and activated protein kinase Cα (PKCα) by phosphorylation. The PKCα activation was involved in the p-cresol-mediated AJ disassembly, since pharmacological inhibition of PKCα abolished the above-mentioned p-cresol effect. This PKCα activation also led to the serine dephosphorylation of p120ctn and caused the dissociation of p120ctn from N-cadherin. This hypothesis was further confirmed in H9c2 cells by siRNA approach. SiRNA knockdown of PKCα prevented p-cresol-induced serine dephosphorylation of p120ctn and splitting of AJ. In conclusion, p-cresol caused PKCα-dependent AJ disassembly of cardiomyocytes, which might be related to asychronized contraction.

The enhancement of security in healthcare information systems.

With the progress and the development of information technology, the internal data in medical organizations have become computerized and are further established the medical information system. Moreover, the use of the Internet enhances the information communication as well as affects the development of the medical information system that a lot of medical information is transmitted with the Internet. Since there is a network within another network, when all networks are connected together, they will form the "Internet". For this reason, the Internet is considered as a high-risk and public environment which is easily destroyed and invaded so that a relevant protection is acquired. Besides, the data in the medical network system are confidential that it is necessary to protect the personal privacy, such as electronic patient records, medical confidential information, and authorization-controlled data in the hospital. As a consequence, a medical network system is considered as a network requiring high security that excellent protections and managerial strategies are inevitable to prevent illegal events and external attacks from happening. This study proposes secure medical managerial strategies being applied to the network environment of the medical organization information system so as to avoid the external or internal information security events, allow the medical system to work smoothly and safely that not only benefits the patients, but also allows the doctors to use it more conveniently, and further promote the overall medical quality. The objectives could be achieved by preventing from illegal invasion or medical information being stolen, protecting the completeness and security of medical information, avoiding the managerial mistakes of the internal information system in medical organizations, and providing the highly-reliable medical information system.

Mobile agent application and integration in electronic anamnesis system.

Electronic anamnesis is to transform ordinary paper trails to digitally formatted health records, which include the patient's general information, health status, and follow-ups on chronic diseases. Its main purpose is to let the records could be stored for a longer period of time and could be shared easily across departments and hospitals. Which means hospital management could use less resource on maintaining ever-growing database and reduce redundancy, so less money would be spent for managing the health records. In the foreseeable future, building up a comprehensive and integrated medical information system is a must, because it is critical to hospital resource integration and quality improvement. If mobile agent technology is adopted in the electronic anamnesis system, it would help the hospitals to make the medical practices more efficiently and conveniently. Nonetheless, most of the hospitals today are still using paper-based health records to manage the medical information. The reason why the institutions continue using traditional practices to manage the records is because there is no well-trusted and reliable electronic anamnesis system existing and accepted by both institutions and patients. The threat of privacy invasion is one of the biggest concerns when the topic of electronic anamnesis is brought up, because the security threats drag us back from using such a system. So, the medical service quality is difficult to be improved substantially. In this case, we have come up a theory to remove such security threats and make electronic anamnesis more appealing for use. Our theory is to integrate the mobile agent technology with the backbone of electronic anamnesis to construct a hierarchical access control system to retrieve the corresponding information based upon the permission classes. The system would create a classification for permission among the users inside the medical institution. Under this framework, permission control center would distribute an access key to each user, so they would only allow using the key to access information correspondingly. In order to verify the reliability of the proposed system framework, we have also conducted a security analysis to list all the possible security threats that may harm the system and to prove the system is reliable and safe. If the system is adopted, the doctors would be able to quickly access the information while performing medical examinations. Hence, the efficiency and quality of healthcare service would be greatly improved.

A mobile agent approach for secure integrated medical information systems.

Different patient-related information in medical organizations is the primary reference for medical personnel diagnosing, treating, and caring patients. With the rapid development of information technology, paper-based medical records have gradually been changed to electronic forms. However, different medical organizations present individual system specifications and data-saving formats so that the medical information of the same patient cannot be exchanged, shared, and securely accessed. In order not to largely change the present medical information systems as well as not to increase abundant costs, Virtual Integrated Medical-information Systems (VIMS) is proposed to assist various hospitals in information exchange. Furthermore, with Mobile Agent, the dispersed medical information can be securely integrated. It presents confidentiality, non-repudiation, source authentication, and integrity in network transmission. Virtual Integrated Medical-information Systems (VIMS) is a virtual electronic integration system combined with Mobile Agent technology. With the features of independence, adaptability, mobility, objectives, and autonomy, Mobile Agent is applied to overcome the problems from heterogeneous systems. With the features, the over-dispersed medical records can be integrated. Moreover, Mobile Agent can ensure the instantaneity and usability of medical records from which doctors can make the most appropriate evaluation and diagnoses. It will avoid the waste of medical resources, such as repetition medication, as well as become the reference of further consultation or health check. Not only can it improve the medical care quality, but it can be provided for medical research.

An adaptive Hinfinity controller design for bank-to-turn missiles using ridge Gaussian neural networks.

A new autopilot design for bank-to-turn (BTT) missiles is presented. In the design of autopilot, a ridge Gaussian neural network with local learning capability and fewer tuning parameters than Gaussian neural networks is proposed to model the controlled nonlinear systems. We prove that the proposed ridge Gaussian neural network, which can be a universal approximator, equals the expansions of rotated and scaled Gaussian functions. Although ridge Gaussian neural networks can approximate the nonlinear and complex systems accurately, the small approximation errors may affect the tracking performance significantly. Therefore, by employing the Hinfinity control theory, it is easy to attenuate the effects of the approximation errors of the ridge Gaussian neural networks to a prescribed level. Computer simulation results confirm the effectiveness of the proposed ridge Gaussian neural networks-based autopilot with Hinfinity stabilization.

Adaptive ultrasonic speckle reduction based on the slope-facet model.

The flat-facet model has been implicitly assumed for the structure of the image surface by most conventional speckle-reduction algorithms. However, this model is rarely found in a real ultrasound (US) image. To preserve the higher order structures and to capture the spatially variant property of the speckle, a new adaptive speckle-reduction algorithm, called the symmetrical speckle-reduction filter (SSRF), was developed based on the slope-facet model. The basic idea of the SSRF was to estimate the uncorrupted signal on the largest symmetrical slope facet centered at each target pixel. The symmetry constraint ensured the correctness of the mean value. An empirical speckle model was incorporated to account for the nature of the speckle in US image. A two-stage despeckling strategy was employed to enhance the statistical reliability of each estimate by forming a union of a set of symmetrical despeckling windows. The proposed SSRF algorithm was compared with two filtered-based and one wavelet-based approaches and the experimental results showed that the proposed SSRF outperformed these three previous approaches in both the synthetic images and the clinical US images tested in this study.

Fuzzy support vector machines.

A support vector machine (SVM) learns the decision surface from two distinct classes of the input points. In many applications, each input point may not be fully assigned to one of these two classes. In this paper, we apply a fuzzy membership to each input point and reformulate the SVMs such that different input points can make different contributions to the learning of decision surface. We call the proposed method fuzzy SVMs (FSVMs).