Nerve trunk healing and neuroma formation after nerve transection injury.

The nerve trunk healing process of a transected peripheral nerve trunk is composed of angiogenesis, nerve fiber regeneration, and scarring. Nerve trunk healing and neuroma formation probably share identical molecular mediators and similar regulations. At the nerve transection site, angiogenesis is sufficient and necessary for nerve fiber regeneration. Angiogenesis and nerve fiber regeneration reveal a positive correlation in the early time. Scarring and nerve fiber regeneration show a negative correlation in the late phase. We hypothesize that anti-angiogenesis suppresses neuromas. Subsequently, we provide potential protocols to test our hypothesis. Finally, we recommend employing anti-angiogenic small-molecule protein kinase inhibitors to investigate nerve transection injuries.

Nobiletin Inhibits Hypoxia-Induced Placental Damage via Modulating P53 Signaling Pathway.

In this study, we aimed to evaluate the effect of Nobiletin (NOB) on the placenta of Sprague-Dawley (SD) rats that had undergone reduced uterine perfusion pressure (RUPP) surgery and to evaluate the safety of NOB intervention during pregnancy. The results showed that NOB alleviated placental hypoxia, attenuated placental cell apoptosis, and inhibited placental damage in RUPP rats. No side effect of NOB intervention during pregnancy was observed. BeWo cell lines with P53 knockdown were then constructed using lentiviral transfection, and the P53 signaling pathway was found to be essential for NOB to reduce hypoxia-induced apoptosis of the BeWo cell lines. In summary, NOB attenuated hypoxia-induced placental damage by regulating the P53 signaling pathway, and those findings may contribute some insights into the role of NOB in placental development and the prevention of placental-related diseases.

Calcium Signaling Regulated by Cellular Membrane Systems and Calcium Homeostasis Perturbed in Alzheimer's Disease.

Although anything that changes spatiotemporally could be a signal, cells, particularly neurons, precisely manipulate calcium ion (Ca2+) to transmit information. Ca2+ homeostasis is indispensable for neuronal functions and survival. The cytosolic Ca2+ concentration ([Ca2+]CYT) is regulated by channels, pumps, and exchangers on cellular membrane systems. Under physiological conditions, both endoplasmic reticulum (ER) and mitochondria function as intracellular Ca2+ buffers. Furthermore, efficient and effective Ca2+ flux is observed at the ER-mitochondria membrane contact site (ERMCS), an intracellular membrane juxtaposition, where Ca2+ is released from the ER followed by mitochondrial Ca2+ uptake in sequence. Hence, the ER intraluminal Ca2+ concentration ([Ca2+]ER), the mitochondrial matrix Ca2+ concentration ([Ca2+]MT), and the [Ca2+]CYT are related to each other. Ca2+ signaling dysregulation and Ca2+ dyshomeostasis are associated with Alzheimer's disease (AD), an irreversible neurodegenerative disease. The present review summarizes the cellular and molecular mechanism underlying Ca2+ signaling regulation and Ca2+ homeostasis maintenance at ER and mitochondria levels, focusing on AD. Integrating the amyloid hypothesis and the calcium hypothesis of AD may further our understanding of pathogenesis in neurodegeneration, provide therapeutic targets for chronic neurodegenerative disease in the central nervous system.

The effects of high-density lipoprotein and oxidized high-density lipoprotein on forskolin-induced syncytialization of BeWo cells.

INTRODUCTION: The negative relationship between maternal high-density lipoprotein-cholesterol (HDL-c) level during pregnancy and infant birth weight has been found. Syncytialization (differentiation and fusion) of trophoblast cells is important to fetal development. HDL has an antioxidant effect, and has been proved to protect trophoblast functions including hormone secretion and invasion. However, HDL is susceptible to oxidation, and high concentrations of HDL impair cell growth and oxidized HDL (oxHDL) inhibits cell proliferation and migration. Moreover, the effects of HDL and oxHDL on trophoblast syncytialization have not been characterized. The aim of this study was to investigate the effects of HDL and oxHDL on trophoblast syncytialization. METHODS: Human choriocarcinoma trophoblasts (BeWo cells) were treated with human HDL or oxHDL and then induced to differentiate by forskolin in syncytialization assays. Expression levels of mRNAs and proteins regulating syncytialization were detected by real-time PCR and western blotting, respectively. RESULTS: Treatments of HDL at high concentrations reduced human chorionic gonadotropin (hCG) secretion, placental alkaline phosphatase activity and fusion rates, and decreased the expressions of GCM1 and ERVW-1 mRNA as well as phospho-MAPK1/3 (p-MAPK1/3) and total MAPK1/3 protein in the forskolin-induced syncytialization of BeWo cells. Furthermore, treatment of oxHDL (20 µg/ml) decreased hCG secretion, but increased the expression of p-MAPK1/3 protein. DISCUSSION: These data suggested that both HDL at high concentrations and oxHDL inhibited BeWo cells syncytialization, and might be harmful to placental and fetal development.

Polymeric Nanoscale Drug Carriers Mediate the Delivery of Methotrexate for Developing Therapeutic Interventions Against Cancer and Rheumatoid Arthritis.

Methotrexate (MTX) is widely used as an anticancer and anti-inflammtory drug for treating various types of cancer and autoimmune diseases. The optimal dose of MTX is known to inhibit the dihydrofolatereductase that hinders the replication of purines. The nanobiomedicine has been extensively explored in the past decade to develop myriad functional nanostructures to facilitate the delivery of therapeutic agents for various medical applications. This review is focused on understanding the design and development of MTX-loaded nanoparticles alongside the inclusion of recent findings for the treatment of cancers. In this paper, we have made a coordinated effort to show the potential of novel drug delivery systems by achieving effective and target-specific delivery of methotrexate.

[Application of near infrared spectroscopy in study of occlusal splints and resistance of masticatory muscles to fatigue pain].

OBJECTIVE: To analyze the influence of occlusal splint on resistance capability of masticatory muscles to fatigue. METHODS: In the study, 25 young male volunteers were randomly divided to 5 groups according to different splint placements: (1) no splint, (2) 1.5 mm thick soft splint, (3) 2 mm thick resin stability splint, (4) 4 mm thick resin stability splint, (5) buccolingual mock splint. Near infrared spectroscopy (NIRS) was used to measure blood oxygen content in human masticatory muscles during constant strong biting before and after the splint placement at seven time points: before, baseline after, 1 week after, and 2 weeks after splint placement, and immediately after, 1 week after, and 5 weeks after removing of splints. The strength of the biting force was maintained constantly at 30% level of the maximum biting force of each subject by biofeedback to the displayed value of an electro-myographic monitor. The time points of muscular fatigue and pain that appeared were recorded and the correlation between the subjective feeling and the NIRS measurement result was analyzed. RESULTS: The NIRS measurement curve had a point of inflection that had no significant difference with the time point of the muscle pain that appeared. Two weeks after placement of soft splint, the time point of the muscular fatigue and pain that appeared were 2.75 s and 8.00 s delayed respectively compared with that before placement of splint (P<0.01) while they were earlier in the groups of hard splints and there was no significant difference (P>0.05) in the group of mock splint. CONCLUSION: The metabolic status of human masticatory muscles could be monitored in real time by using NIRS; soft splint delayed the appearing of muscle fatigue and muscle pain after two weeks of placement.