X-irradiation reduces the proliferation of astrocytes by cell cycle arrest.

Reactive astrogliosis is one of the key components of the cellular response to CNS injury and is considered a major impediment to axonal regeneration. Our previous study demonstrated that cell cycle inhibition treatment can reduce astrocyte activation and proliferation in vivo. In this study, we examined whether reactive astrogliosis can be suppressed by X-irradiation in vitro by modulating cell cycle progression.

Galectin-1 attenuates astrogliosis-associated injuries and improves recovery of rats following focal cerebral ischemia.

Astrogliosis occurs after brain ischemia, and excessive astrogliosis can devastate the neuronal recovery. Previous reports show that galectin-1 (Gal-1) regulates proliferation of several cell types and plays an important role after nervous system injuries. Here, we found that expression of Gal-1 was remarkably up-regulated in activated astrocytes around ischemic infarct.

Galectin-1 enhances astrocytic BDNF production and improves functional outcome in rats following ischemia.

Galectin-1, an endogenous mammalian lectin, has been implicated in a variety of CNS disorders. However, its role in cerebral ischemia is still elusive. In the present study, we investigated the effect of recombinant galectin-1 on production of astrocytic brain-derived neurotrophic factor (BDNF) and functional recovery following ischemia.

[Preparation of bovine serum albumin immobilized adsorbent for specific adsorption of bilirubin].

Serum bilirubin concentration is greatly elevated in certain diseases such as hyperbilirubinemia and severe hepatitis. Lowering the level of bilirubin is one of the major targets of many therapies such as plasma exchange and hemoperfusion. In this study, a bilirubin specific adsorbent was prepared by covalently immobilizing bovine serum albumin (BSA) onto macroporous poly (glycidyl methacrylate-co-trimethylolpropane trimethacrylate) microspheres.

Proliferation and differentiation of neural stem cells are selectively regulated by knockout of cyclin D1.

Although stem cells can proliferate and differentiate through the completion of cell cycle progression, little is known about the genes and molecular mechanisms controlling this process. Here, we investigated the effect of the inhibition of cell cycle by cyclin D1 gene knockout on proliferation and differentiation of neural stem cells (NSCs). Knockout of cyclin D1 induced the cultured neural stem cells arrested at the G0/G1 phase as detected by flow cytometry.

Preparation of polyamine-functionalized copper specific adsorbents for selective adsorption of copper.

The level of serum free copper is greatly elevated in Wilson's disease. For patients with acute Wilson's disease, liver transplantation is the only lifesaving treatment. Plasma exchange or albumin dialysis is often used as a bridge to liver transplantation to maintain a stable clinical status for patients.

CREB trans-activation of disruptor of telomeric silencing-1 mediates forskolin inhibition of CTGF transcription in mesangial cells.

Connective tissue growth factor (CTGF) participates in diverse fibrotic processes including glomerulosclerosis. The adenylyl cyclase agonist forskolin inhibits CTGF expression in mesangial cells by unclear mechanisms. We recently reported that the histone H3K79 methyltransferase disruptor of telomeric silencing-1 (Dot1) suppresses CTGF gene expression in collecting duct cells (J Clin Invest 117: 773-783, 2007) and HEK 293 cells (J Biol Chem In press).

Tamoxifen alleviates irradiation-induced brain injury by attenuating microglial inflammatory response in vitro and in vivo.

Irradiation-induced brain injury, leading to cognitive impairment several months to years after whole brain irradiation (WBI) therapy, is a common health problem in patients with primary or metastatic brain tumor and greatly impairs quality of life for tumor survivors. Recently, it has been demonstrated that a rapid and sustained increase in activated microglia following WBI led to a chronic inflammatory response and a corresponding decrease in hippocampal neurogenesis. Tamoxifen, serving as a radiosensitizer and a useful agent in combination therapy of glioma, has been found to exert anti-inflammatory response both in cultured microglial cells and in a spinal cord injury model.

Reversed-phase-reversed-phase liquid chromatography approach with high orthogonality for multidimensional separation of phosphopeptides.

Protein phosphorylation regulates a series of important biological processes in eukaryotes. However, the phosphorylation sites found up to now are far below than that actually exists in proteins due to the extreme complexity of the proteome sample. Here a new reversed-phase-reversed-phase liquid chromatography (RP-RPLC) approach was developed for multidimensional separation of phosphopeptides.

Neural cell cycle dysregulation and central nervous system diseases.

The cell cycle is a delicately manipulated process essential for the development, differentiation, proliferation and death of cells. Inappropriate activation of cell cycle regulators is implicated in the pathophysiology of a wide range of central nervous system (CNS) diseases, including both acute damage and chronic neurodegenerative disorders. Cell cycle activation induces the dividing astrocytes and microglia to activate and proliferate in association with glial scar formation and inflammatory factor production, which play crucial roles in the development of pathology in CNS diseases.

Tamoxifen attenuates inflammatory-mediated damage and improves functional outcome after spinal cord injury in rats.

Tamoxifen has been found to be neuroprotective in both transient and permanent experimental ischemic stroke. However, it remains unknown whether this agent shows a similar beneficial effect after spinal cord injury (SCI), and what are its underlying mechanisms. In this study, we investigated the efficacy of tamoxifen treatment in attenuating SCI-induced pathology.

Sp1 trans-activates the murine H(+)-K(+)-ATPase alpha(2)-subunit gene.

The H(+)-K(+)-ATPase alpha(2) (HKalpha2) gene of the renal collecting duct and distal colon plays a central role in potassium and acid-base homeostasis, yet its transcriptional control remains poorly characterized. We previously demonstrated that the proximal 177 bp of its 5'-flanking region confers basal transcriptional activity in murine inner medullary collecting duct (mIMCD3) cells and that NF-kappaB and CREB-1 bind this region to alter transcription. In the present study, we sought to determine whether the -144/-135 Sp element influences basal HKalpha2 gene transcription in these cells.

Preparation of monodisperse immobilized Ti(4+) affinity chromatography microspheres for specific enrichment of phosphopeptides.

This study presented an approach to prepare monodisperse immobilized Ti(4+) affinity chromatography (Ti(4+)-IMAC) microspheres for specific enrichment of phosphopeptides in phosphoproteome analysis. Monodisperse polystyrene seed microspheres with a diameter of ca. 4.

The involvement of upregulation and translocation of phospho-Rb in early neuronal apoptosis following focal cerebral ischemia in rats.

The aim of this study was to investigate the temporal and spatial relationship between phospho-Rb (ser 795) and neuronal apoptotic death in rats subjected to transient focal cerebral ischemia. We found increased phosphorylation of Rb and translocation from neuronal nucleus to cytoplasm in the penumbra zone at 12 h, 1 day, 3 days and 7 days after middle cerebral artery occlusion (MCAO)/reperfusion, compared with sham-operated controls. At 12 h and 1 day, phospho-Rb appeared to be colocalizated with TUNEL staining in neurons, but staining was not colocalizated at 3 days and 7 days.

Cell cycle inhibition attenuates microglial proliferation and production of IL-1beta, MIP-1alpha, and NO after focal cerebral ischemia in the rat.

We recently showed that suppressing cell cycle progression inhibited reactive astrogliosis and promoted neuronal survival in an acute focal cerebral ischemia rat model. However, it remains unclear whether and to what extent the beneficial effects of cell cycle inhibition might also be attributed to the inhibition of microglial proliferation and cytokine/chemokine production. In this study, we showed that application of the cell cycle inhibitor roscovitine before middle carotid artery occlusion (MCAO) in the rat inhibited microglial proliferation and cytokine/chemokine production, and reduced the number of cell-cycle-related proteins including cyclin A, cyclin B, and cyclin E.

Epigenetics and the control of epithelial sodium channel expression in collecting duct.

In eukaryotic nuclei, genomic DNA is compacted with histone and nonhistone proteins into a dynamic polymer termed chromatin. Reorganization of chromatin structure through histone modifications, the action of chromatin factors, or DNA methylation, can profoundly change gene expression. These epigenetic modifications allow heritable and potentially reversible changes in gene functioning to occur without altering the DNA sequence, thus extending the information potential of the genetic code.

Astrocytes facilitate the growth and differentiation of co-cultured mesenchymal stem cells.

The effect of astrocytes on the growth and differentiation of co-cultured mesenchymal stem cells (MSCs) was studied. MSCs of Wistar rats were isolated, cultured and labeled with Hoechst33342. The labeled MSCs were co-cultured with astrocytes in DMEM/F12/10%FBS.

New mechanisms for transcriptional repression of ENaC And iNOS.

Gene transcription is highly regulated to ensure that specific genes are expressed at the appropriate times, places and levels in response to various genetic and environmental stimuli. Activation of some genes occurs by relief of basal repression controls, whereas termination of active transcription can involve feedback inhibition. We describe our characterization of aldosterone-triggered de-repression of the epithelial Na(+) channel-alpha subunit (ENaCalpha) gene in renal collecting duct cells in a process that involves a novel nuclear repressor complex, consisting of a histone H3 K79 methyltransferase and the putative transcription factor AF9, that regulates targeted histone H3 K79 methylation at the ENaCalpha promoter.

Rat focal cerebral ischemia induced astrocyte proliferation and delayed neuronal death are attenuated by cyclin-dependent kinase inhibition.

Astroglial proliferation and delayed neuronal death are two common pathological processes in the ischemic brain. However, it is not clear if astrogliosis causes delayed neuronal death. In this study, we addressed this potential linkage by examining the relationship between attenuated astrocyte proliferation, induced by cyclin-dependent kinase (CDK) inhibition, and delayed neuronal death in rat ischemic hippocampus.

[Effects of cyclin dependent protein kinase inhibitor olomoucine on the neuronal apoptosis after status epilepticus: experiment with rats].

Objective: To investigate the effects of olomoucine, a cyclin dependent protein kinase (CDK) inhibitor, on the neuronal apoptosis after status epilepticus (SE).

Methods: Lithium chloride was injected intraperitoneally, and pilocarpine was injected intraperitoneally after 18 h to 24 SD rats so as to cause SE. Twenty-two of the 24 rats developed SE and 2 of them died.

Unwanted sexual activity among married women in urban China.

This paper examines the prevalence, precursors, and consequences of unwanted marital sex activities in a national sample of 1,127 married urban Chinese women aged 20-64. During the lifetime of their current marriage, 32% reported ever experiencing unwanted spousal intercourse, with about one-fifth reporting that this unwanted intercourse ever involved force. Reports for the past year were 21% unwanted intercourse, 22% unwanted sex act(s), and 72% sex only to please the husband.

Attenuation of astrogliosis by suppressing of microglial proliferation with the cell cycle inhibitor olomoucine in rat spinal cord injury model.

Microglial activation/proliferation and reactive astrogliosis are commonly observed and have been considered to be closely relevant pathological processes during spinal cord injury (SCI). However, the molecular mechanisms underlying this microglial-astroglial interaction are still poorly understood. We showed recently that the continuous injection of the cell cycle inhibitor olomoucine not only markedly suppressed microglial proliferation and associated release of pro-inflammatory cytokines, but also attenuated astroglial scar formation and the lesion cavity and mitigated the functional deficits in rat SCI animal model.

Inhibiting cell cycle progression reduces reactive astrogliosis initiated by scratch injury in vitro and by cerebral ischemia in vivo.

Astrogliosis occurs in a variety of neuropathological disorders and injuries, and excessive astrogliosis can be devastating to the recovery of neuronal function. In this study, we asked whether reactive astrogliosis can be suppressed in the lesion area by cell cycle inhibition and thus have therapeutic benefits. Reactive astrogliosis induced in either cultured astrocytes by hypoxia or scratch injury, or in a middle cerebral artery occlusion (MCAO) ischemia model were combined to address this issue.

Cell cycle inhibition attenuates microglia induced inflammatory response and alleviates neuronal cell death after spinal cord injury in rats.

The spinal cord is well known to undergo inflammatory reactions in response to traumatic injury. Activation and proliferation of microglial cells, with associated proinflammatory cytokines expression, plays an important role in the secondary damage following spinal cord injury. It is likely that microglial cells are at the center of injury cascade and are targets for treatments of CNS traumatic diseases.