Origin of Secretin Receptor Precedes the Advent of Tetrapoda: Evidence on the Separated Origins of Secretin and Orexin

At present, secretin and its receptor have only been identified in mammals, and the origin of this ligand-receptor pair in early vertebrates is unclear. In addition, the elusive similarities of secretin and orexin in terms of both structures and functions suggest a common ancestral origin early in the vertebrate lineage. In this article, with the cloning and functional characterization of secretin receptors from lungfish and X. laevis as well as frog (X. laevis and Rana rugulosa) secretins, we provide evidence that the secretin ligand-receptor pair has already diverged and become highly specific by the emergence of tetrapods. The secretin receptor-like sequence cloned from lungfish indicates that the secretin receptor was descended from a VPAC-like receptor prior the advent of sarcopterygians. To clarify the controversial relationship of secretin and orexin, orexin type-2 receptor was cloned from X. laevis. We demonstrated that, in frog, secretin and orexin could activate their mutual receptors, indicating their coordinated complementary role in mediating physiological processes in non-mammalian vertebrates. However, among the peptides in the secretin/glucagon superfamily, secretin was found to be the only peptide that could activate the orexin receptor. We therefore hypothesize that secretin and orexin are of different ancestral origins early in the vertebrate lineage

Nanotechnology in bladder cancer: current state of development and clinical practice

Nanotechnology is being developed for the diagnosis and treatment of both nonmyoinvasive bladder cancer (NMIBC) and invasive bladder cancer. The diagnostic applications of nanotechnology in NMIBC mainly focus on tumor identification during endoscopy to increase complete resection of bladder cancer while nanotechnology to capture malignant cells or their components continues to be developed. The therapeutic applications of nanotechnology in NMIBC are to reformulate biological and cytotoxic agents for intravesical instillation, combine both diagnostic and therapeutic application in one nanoformulation. In invasive and advanced bladder cancer, magnetic resonance imaging with supraparamagnetic iron oxide nanoparticles can improve the sensitivity and specificity in detecting small metastasis to lymph nodes. Nanoformulation of cytotoxic agents can potentially decrease the toxicity while increasing efficacy

Evidence-based and heuristic approaches for customization of care in cardiometabolic syndrome after spinal cord injury

Component and coalesced health risks of the cardiometabolic syndrome (CMS) are commonly reported in persons with spinal cord injuries (SCIs). These CMS hazards are also co-morbid with physical deconditioning and elevated pro-atherogenic inflammatory cytokines, both of which are common after SCI and worsen the prognosis for all-cause cardiovascular disease. This article describes a systematic procedure for individualized CMS risk assessment after SCI, and emphasizes evidence-based and intuition-centered countermeasures to disease. A unified approach will propose therapeutic lifestyle intervention as a routine plan for aggressive primary prevention in this risk-susceptible population. Customization of dietary and exercise plans then follow, identifying shortfalls in diet and activity patterns, and ways in which these healthy lifestyles can be more substantially embraced by both stakeholders with SCI and their health care providers. In cases where lifestyle intervention utilizing diet and exercise is unsuccessful in countering risks, available pharmacotherapies and a preferred therapeutic agent are proposed according to authoritative standards. The over-arching purpose of the monograph is to create an operational framework in which existing evidence-based approaches or heuristic modeling becomes best practice. In this way persons with SCI can lead more active and healthy lives