Live-cell imaging of human apurinic/apyrimidinic endonuclease 1 in the nucleus and nucleolus using a chaperone@DNA probe.

Human apurinic/apyrimidinic endonuclease 1 (APE1) plays crucial roles in repairing DNA damage and regulating RNA in the nucleus. However, direct visualization of nuclear APE1 in live cells remains challenging. Here, we report a chaperone@DNA probe for live-cell imaging of APE1 in the nucleus and nucleolus in real time.

Exploring the Complex Impact of Proteins on Dopamine Polymerization: Mechanisms and Strategies for Modulation.

Polydopamine (pDA) is a valuable material with wide-ranging potential applications. However, the complex and debated nature of dopamine polymerization complicates our understanding. Specifically, the impact of foreign substances, especially proteins, on pDA formation adds an additional layer of subtlety and complexity.

Surface imprinted bio-nanocomposites for affinity separation of a cellular DNA repair protein.

Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional DNA repair protein localized in different subcellular compartments. The mechanisms responsible for the highly regulated subcellular localization and "interactomes" of this protein are not fully understood but have been closely correlated to the posttranslational modifications in different biological context. In this work, we attempted to develop a bio-nanocomposite with antibody-like properties that could capture APE1 from cellular matrices to enable the comprehensive study of this protein.

Programmable One-Pot Enzymatic Reaction for Direct Fluorescence Detection of Ultralow-Abundance Mutations in the DNA Duplex.

Sensitive detection of low-abundance driver mutations may provide valuable information for precise clinical treatment. Compared to next-generation sequencing and droplet digital PCR methods, fluorescent probes show great flexibility in rapid detection of specific mutations with high sensitivity and easily accessible instruments. However, existing approaches with fluorescent probes need an additional step to convert duplex DNA to single-stranded DNA (ssDNA) before the detection step, which increases the time, cost, and risk of loss of low-input target strands.

Mesenchymal stromal cell-derived exosomes ameliorate peripheral neuropathy in a mouse model of diabetes.

Aims/hypothesis: Diabetic peripheral neuropathy (DPN) is one of the major complications of diabetes, which contributes greatly to morbidity and mortality. There is currently no effective treatment for this disease. Exosomes are cell-derived nanovesicles and play an important role in intercellular communications.

Ablation of the microRNA-17-92 cluster in neural stem cells diminishes adult hippocampal neurogenesis and cognitive function.

Impairment of adult neurogenesis in the hippocampus causes cognitive deficits; however, the underlying molecular mechanisms have not been fully elucidated. microRNAs (miRNAs) regulate neural stem cell (NSC) function. With the use of a transgenic mouse line with conditional ablation of the miR-17-92 cluster in nestin lineage NSCs, we tested the hypothesis that the miR-17-92 cluster regulates adult neurogenesis and cognitive function in vivo.

Influence of Sex on Cognition and Peripheral Neurovascular Function in Diabetic Mice.

Cognition impairment and peripheral neuropathy (DPN) are two major complications of diabetes. The aim of the present study is to investigate the effect of sex differences on cognition and DPN in diabetic mice. Male and female BKS.

MicroRNA-146a Mimics Reduce the Peripheral Neuropathy in Type 2 Diabetic Mice.

MicroRNA-146a (miR-146a) regulates multiple immune diseases. However, the role of miR-146a in diabetic peripheral neuropathy (DPN) has not been investigated. We found that mice () with type 2 diabetes exhibited substantial downregulation of miR-146a in sciatic nerve tissue.

Function of neural stem cells in ischemic brain repair processes.

Hypoxic/ischemic injury is the single most important cause of disabilities in infants, while stroke remains a leading cause of morbidity in children and adults around the world. The injured brain has limited repair capacity, and thereby only modest improvement of neurological function is evident post injury. In rodents, embryonic neural stem cells in the ventricular zone generate cortical neurons, and adult neural stem cells in the ventricular-subventricular zone of the lateral ventricle produce new neurons through animal life.

Therapeutic Benefit of Extended Thymosin β4 Treatment Is Independent of Blood Glucose Level in Mice with Diabetic Peripheral Neuropathy.

Peripheral neuropathy is a chronic complication of diabetes mellitus. To investigated the efficacy and safety of the extended treatment of diabetic peripheral neuropathy with thymosin β4 (Tβ4), male diabetic mice (db/db) at the age of 24 weeks were treated with Tβ4 or saline for 16 consecutive weeks. Treatment of diabetic mice with Tβ4 significantly improved motor (MCV) and sensory (SCV) conduction velocity in the sciatic nerve and the thermal and mechanical latency.

Sildenafil ameliorates long term peripheral neuropathy in type II diabetic mice.

Diabetic peripheral neuropathy is a common complication of long-standing diabetes mellitus. To mimic clinical trials in which patients with diabetes enrolled have advanced peripheral neuropathy, we investigated the effect of sildenafil, a specific inhibitor of phosphodiesterase type 5 enzyme, on long term peripheral neuropathy in middle aged male mice with type II diabetes. Treatment of diabetic mice (BKS.

B7-H1 and B7-H4 expression in colorectal carcinoma: correlation with tumor FOXP3(+) regulatory T-cell infiltration.

B7-H1 and B7-H4 are newly discovered members of the B7-CD28 family. They can inhibit T cell activation and proliferation and regulate T cell immune response negatively. Both B7-H1 and B7-H4 are expressed in many tumors and are classified as co-inhibitors of cell-mediated immunity.

Oligodendrogenesis after cerebral ischemia.

Neural stem cells in the subventricular zone (SVZ) of the lateral ventricle of adult rodent brain generate oligodendrocyte progenitor cells (OPCs) that disperse throughout the corpus callosum and striatum where some of OPCs differentiate into mature oligodendrocytes. Studies in animal models of stroke demonstrate that cerebral ischemia induces oligodendrogenesis during brain repair processes. This article will review evidence of stroke-induced proliferation and differentiation of OPCs that are either resident in white matter or are derived from SVZ neural progenitor cells and of therapies that amplify endogenous oligodendrogenesis in ischemic brain.

[Knowledge and attitude of clinicians to pediatric obstructive sleep apnea hypopnea syndrome].

Objective: To investigate the knowledge and attitude of clinicians in the departments of pediatrics and otolaryngology to pediatric obstructive sleep apnea hypopnea syndrome (OSAHS), since in China, the clinicians in these two departments had closest relationship with the diagnosis and treatment of OSAHS in children.

Methods: A validated questionnaire from USA which was the obstructive sleep apnea knowledge and attitudes questionnaire in children (OSAKA-KIDS) was used and permission by original author. The questionnaire was mailed to ENT doctors and pediatricians in 43 public hospitals in Shandong province.

Cerebrolysin enhances neurogenesis in the ischemic brain and improves functional outcome after stroke.

Cerebrolysin is a peptide preparation mimicking the action of neurotrophic factors and has beneficial effects on neurodegenerative diseases and stroke. The present study investigated the effect of Cerebrolysin on neurogenesis in a rat model of embolic middle cerebral artery occlusion (MCAo). Treatment with Cerebrolysin at doses of 2.

Ischemic cerebral tissue response to subventricular zone cell transplantation measured by iterative self-organizing data analysis technique algorithm.

To investigate the changes of the ischemic lesion in rat brain after subventricular zone (SVZ) cell transplantation and the influence of the grafted cells on the appearance of angiogenesis, SVZ cells, superparamagnetically labeled, were intracisternally transplanted into the rat brain 48 h after onset of embolic stroke. A complete set of magnetic resonance (MR) images was acquired for all animals with (n=8) and without (n=3) cell grafting at approximately 24 h, 72 h, and weekly for 6 weeks after stroke. Transplanted cells were tracked by high-resolution three-dimensional gradient-echo images and the interaction between the cells and ischemic lesion was detected by ISODATA (Iterative Self-Organizing Data Analysis Technique Algorithm) calculated from T(1), T(2) and T(1sat) maps.

Biphasic effects of exogenous VEGF on VEGF expression of adult neural progenitors.

Vascular endothelial growth factor (VEGF) regulates neurogenesis. The present study investigated the direct effect of VEGF on the enhancement of proliferation and differentiation of the adult mouse subventricular zone (SVZ) neural progenitors in vitro. A high dose (500 ng/ml) of VEGF significantly downregulated endogenous VEGF receptors 1 and 2, which was associated with significantly reduced neural progenitor cell proliferation and enhancement of neuronal differentiation.

Investigation of neural progenitor cell induced angiogenesis after embolic stroke in rat using MRI.

Using MRI, we investigated dynamic changes of brain angiogenesis after neural progenitor cell transplantation in the living adult rat subjected to embolic stroke. Neural progenitor cells isolated from the subventricular zone (SVZ) of the adult rat were labeled by superparamagnetic particles and intracisternally transplanted into the adult rat 48 h after stroke (n = 8). Before and after the transplantation, an array of MRI parameters were measured, including high resolution 3D MRI and quantitative T1, T1sat (T1 in the presence of an off-resonance irradiation of the macromolecules of brain), T2, the inverse of the apparent forward transfer rate for magnetization transfer (kinv), cerebral blood flow (CBF), cerebral blood volume (CBV), and blood-to-brain transfer constant (Ki) of Gd-DTPA.

In vivo magnetic resonance imaging tracks adult neural progenitor cell targeting of brain tumor.

Using magnetic resonance imaging (MRI), we described a method for noninvasively tracking grafted neural progenitor cells and bone marrow stromal cells (MSCs) in brain tumor of the rat. Neural progenitor cells and MSCs were labeled with lipophilic dye-coated superparamagnetic particles. The labeled neural progenitor cells and MSCs were transplanted to rats via the cisterna magna and a tail vein, respectively, 1 week after 9L-gliosarcoma cell implantation.

Down-regulation of p27kip1 increases proliferation of progenitor cells in adult rats.

Cyclin-dependent kinases (CDK) mediate the cell division cycle during G1 phase and CDK inhibitors negatively regulate the cell cycle. We investigated expression of the CDK inhibitor p27Kip1 and the effects of PI-3K/Akt on proliferation of progenitors in the subventricular zone of adult rat. Western blots and immunostaining revealed that 4 days after stroke, p27kip1 levels decreased and were absent in nuclei of the ipsilateral subventricular zone cells 7 days after stroke.

Stroke transiently increases subventricular zone cell division from asymmetric to symmetric and increases neuronal differentiation in the adult rat.

The orientation of mitotic cleavage regulates neurogenesis during neural development. We examined the orientation of mitotic cleavage of dividing progenitor cells in the subventricular zone (SVZ) of adult rats subjected to stroke. In nonstroke rats, 55% of dividing cells were oriented horizontally, whereas 40% were oriented vertically.

Treatment of stroke with erythropoietin enhances neurogenesis and angiogenesis and improves neurological function in rats.

Background And Purpose: Erythropoietin (EPO) promotes proliferation and differentiation of erythroid progenitors and the survival of maturing erythroid cells. Here, we investigated the role of EPO in brain repair after stroke.

Methods: Rats were treated with recombinant human EPO (rhEPO) at 24 hours after the onset of embolic stroke.

Erythropoietin up-regulates SOCS2 in neuronal progenitor cells derived from SVZ of adult rat.

We examined the effects of EPO on expression of suppressor of cytokine signaling 2 (SOCS2) and found that treatment of neural progenitor cells derived from the adult subventricular zone (SVZ) with recombinant human EPO (rhEPO) stimulated progenitor cell differentiation into neurons, but not astrocytes. Quantitative RT-PCR revealed that SOCS2 mRNA levels were increased in the progenitor cells treated with rhEPO. Immunostaining showed that neurons but not astrocytes were SOCS2 immunoreactive.

Activated neural stem cells contribute to stroke-induced neurogenesis and neuroblast migration toward the infarct boundary in adult rats.

Stroke increases neurogenesis. The authors investigated whether neural stem cells or progenitor cells in the adult subventricular zone (SVZ) of rats contribute to stroke-induced increase in neurogenesis. After induction of stroke in rats, the numbers of cells immunoreactive to doublecortin, a marker for immature neurons, increased in the ipsilateral SVZ and striatum.