Bollreynolds5053

V.Solute carriers (SLCs) are the largest family of transmembrane transporters that determine the exchange of various substances, including nutrients, ions, metabolites, and drugs across biological membranes. To date, the presence of about 287 SLC genes have been identified in the brain, among which mutations or the resultant dysfunctions of 71 SLC genes have been reported to be correlated with human brain disorders. Although increasing interest in SLCs have focused on drug development, SLCs are currently still under-explored as drug targets, especially in the brain. We summarize the main substrates and functions of SLCs that are expressed in the brain, with an emphasis on selected SLCs that are important physiologically, pathologically, and pharmacologically in the blood-brain barrier, astrocytes, and neurons. Evidence suggests that a fraction of SLCs are regulated along with the occurrences of brain disorders, among which epilepsy, neurodegenerative diseases, and autism are representative. Given the review of SLCs involved in the onset and procession of brain disorders, we hope these SLCs will be screened as promising drug targets to improve drug delivery to the brain. © 2019 Shenyang Pharmaceutical University. Published by Elsevier B.V.Stability of space frame structures with bone cement screw reinforcement by biomechanical testing was analyzed. Seven complete human spine specimens with osteoporosis were selected. Three specimens were separated into 18 vertebral bodies. Nine vertebral bodies were randomly selected and bone cement screws were implanted on both sides. Bone cement was used to form a bridge at the front end of the two screws (single vertebral group A). The other nine vertebral bodies were implanted with cement screws on both sides, but the front ends of the two screws were not bridged (single vertebral group B). https://www.selleckchem.com/products/Carboplatin.html The remaining spine specimens were used for biomechanical testing of the overall stability of the three-dimensional frame. The four specimens were osteotomized, and then two specimens were randomly selected. Bone cement screws were implanted on both sides of the vertebral body, and a bone cement bridge was formed at the front end of the two screws to establish a three-dimensional frame structure (multi-vertebral group A). The other two spine specimens were implanted with cement screws on both sides of the vertebral body, but the front ends of the two screws were not bridged (multi-vertebral group B). A statistical difference was found between the extractive force of bridged and non-bridged specimens. Group B showed some loosening of screws after the test. The stability of the triangle structure screw, which was formed after the bridge was established at the front end of the single-vertebral bone cement screw, was significantly enhanced. Moreover, the stability was significantly improved after the three-dimensional frame structure was established in the multi-vertebral body group, providing a new method for clinical improvement of the stability and reliability of internal fixation in patients with severe osteoporosis and spinal disease. Copyright © Xiu et al.The aim of the study was to observe the effects of Tougu Xiaotong capsule (TGXTC) on the microstructure and ultrastructure of meniscus in rats with early knee osteoarthritis (KOA). A total of 27 Sprague Dawley rats were randomly divided into three groups The normal group (non-papain-induced KOA; received saline only), the model group (papain-induced KOA; received saline only) and the TGXTC group [papain-induced KOA; received TGXTC (0.31g·kg-1·d-1)]. After 4 weeks treatment, the animals were anesthetized and the sagittal plane of the intact knees (n=6 per group) was obtained and prepared in paraffin section. Following hematoxylin and eosin staining, the degeneration of cartilage structure was evaluated via Mankin score, the microstructure of meniscus was observed and the area of calcification in meniscus was analyzed. Following toluidine blue staining, the content of proteoglycan in meniscus was analyzed. Three samples in each group were obtained and the ultrathin sections of meniscus were observed through a t endoplasmic reticulum, mitochondria and Golgi apparatus of meniscal cartilage were reduced and swollen in the model group. In addition, the nuclei were deformed and heterochromatin agglutinated. The extracellular collagen fibrils became slender, disordered and sparse. Compared with the model group, the TGXTC group had more cell processes and organelles, alleviated swelling and heterochromatin agglutinating. Additionally, the collagen fibrils around the cells were thicker, larger and arranged in an orderly manner. In conclusion, TGXTC exerted its therapeutic effects on the development of KOA via reducing the destruction of the cartilage structure of the meniscus and improving the composition and function of the meniscus cartilage matrix. Copyright © Wu et al.Excessive vascular smooth muscle cell (VSMC) proliferation contributes to the development of atherosclerosis and restenosis. Furthermore, apoptosis of VSMCs accelerates plaque rupture in the atherosclerotic vessels. Therefore, a strategy that regulates both VSMC proliferation and apoptosis is essential for the development of novel pharmacological tools for the treatment of atherosclerosis. Despite mounting evidence supporting the benefits of melatonin in diverse metabolic diseases, the role of melatonin in VSMC growth remains largely unknown. The present study revealed that melatonin inhibited both proliferation and apoptosis of primary cultured rat VSMCs. Melatonin induced mitochondrial energetic stress in VSMCs and subsequent induction of Sestrin2 via C/EBPβ. Melatonin-induced Sestrin2 suppressed mTORC1 activity in VSMCs, contributing to suppression of VSMC proliferation. Additionally, melatonin-induced upregulation of Sestrin2 blocked apoptosis by preventing excessive ROS generation. The results demonstrated that melatonin controlled VSMC proliferation and apoptosis via Sestrin2-mediated inhibition of mTORC1 and ROS scavenging. Therefore, melatonin should be considered as a lead compound for therapies aimed at preventing vessel lumen constriction during the course of atherosclerosis and restenosis. Copyright © Lee et al.