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Abstract: Decreased cerebral blood flow causes cognitive impairments and neuronal injury in vascular dementia. In the present study, we reported that donepezil, a cholinesterase inhibitor, improved transient global cerebral ischemia-induced spatial memory impairment in gerbils. Treatment with 5mg/kg of donepezil for 21 consecutive days following a 10-min period of ischemia significantly inhibited delayed neuronal death in the hippocampal CA1 region. In Morris water maze test, memory impairment was significantly improved by donepezil treatment. Western blot analysis showed that donepezil treatment prevented reductions in p-CaMKII and p-CREB protein levels in the hippocampus. These results suggest that donepezil attenuates the memory deficit induced by transient global cerebral ischemia and this neuroprotection may be associated with the phosphorylation of CaMKII and CERB in the hippocampus. [Copyright &y& Elsevier]

Abstract: Impaired GABAergic inhibitory neurotransmission plays an essential role in the pathogenesis of epilepsy. GABAA receptor (GABAAR), potassium chloride cotransporter 2 (KCC2) and astrocytes are of particular importance to GABAergic transmission and thus involved in the development of increased seizure susceptibility. The tremor rat (TRM: tm/tm), a genetic mutant discovered in a Kyoto–Wistar colony, can manifest both absence-like seizures and tonic convulsions without any external stimuli. So far, there are no reports that can elucidate the effects of GABAAR (α4, γ2 subunit), KCC2 and astrocytes on TRMs. The present study was undertaken to detect the expressions of GABAAR α4, GABAAR γ2 and KCC2 in TRMs hippocampus at mRNA and protein levels. In this work, mRNA and protein expressions of GABAAR α4 were significantly elevated while GABAAR γ2 and KCC2 were both evidently decreased in TRMs hippocampus by real-time RT-PCR and western blot, respectively. Furthermore, a dramatic elevation of KCC2 protein level was found after cerebroventricular injection with K252a to TRMs than that in the DMSO-treated TRMs. Besides, our present study also demonstrated that GFAP (a major component of astrocyte) immunoreactivity was much more intense in TRMs hippocampal CA1, CA3 and DG regions than that in control group with immnohistochemistry and confocal microscopic analyses. The protein expression of GFAP was also markedly elevated in TRMs hippocampus, suggesting that astrogliosis appeared in the TRM model. These data demonstrate that altered expressions of GABAAR (α4, γ2) and KCC2 and astrogliosis observed in TRMs hippocampus may provide us good therapeutic targets for the treatment of genetic epilepsy. [Copyright &y& Elsevier]

Abstract: Baicalin is an important medicinal herb purified from the dry roots of Scutellaria baicalensis Georgi. The present study was undertaken to evaluate the neuroprotective effects of baicalin in gerbils subjected to transient global cerebral ischemic–reperfusion injury. Baicalin at doses of 50, 100 and 200mg/kg was intraperitoneally injected into the gerbils immediately after cerebral ischemia. Seven days after reperfusion, hematoxylin and eosin (HE) staining was performed to analyze hippocampal CA1 pyramidal damage histopathologically. In addition, in order to understand the potential protective mechanism of baicalin, we examined anti-oxidative enzymes, such superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), non-enzymatic scavenger glutathione (GSH) and measured the content of malondialdehyde (MDA) in hippocampus. The mRNA and protein expressions of BDNF were determined in ischemic hippocampus by real-time RT-PCR and Western blot, respectively. Evidence for neuronal apoptosis was detected by real-time RT-PCR, Western blot and caspase-3 activity measurement. Histopathological examination showed that the administration of baicalin by the dose of 100 and 200mg/kg significantly attenuated ischemia-induced neuronal cell damage. Reduced level of MDA, obviously elevated activities of SOD and GSH as well as GSH-PX were also found in baicalin-treated groups. Further investigation demonstrated that treatment with baicalin remarkably promoted the expression of BDNF and inhibited the expression of caspase-3 at mRNA and protein levels by real-time RT-PCR and Western blot, respectively. Besides, caspase-3 activity assay also elucidated that the administration of baicalin could significantly suppress caspase-3 in ischemic gerbils hippocampus. Theses findings suggest that baicalin''s neuroprotection appears to be associated with its anti-oxidative and anti-apoptotic properties in global cerebral ischemia in the gerbils. [Copyright &y& Elsevier]

Abstract: The loss of GABAergic neurotransmission has been closely linked with epileptogenesis. The modulation of the synaptic activity occurs both via the removal of GABA from the synaptic cleft and by GABA transporters (GATs) and by modulation of GABA receptors. The tremor rat (TRM; tm/tm) is the parent strain of the spontaneously epileptic rat (SER; zi/zi, tm/tm), which exhibits absence-like seizure after 8 weeks of age. However, there are no reports that can elucidate the effects of GATs and GABAA receptors (GABARs) on TRMs. The present study was conducted to detect GATs and GABAR α1 subunit in TRMs hippocampus at mRNA and protein levels. In this study, total synaptosomal GABA content was significantly decreased in TRMs hippocampus compared with control Wistar rats by high performance liquid chromatography (HPLC); mRNA and protein expressions of GAT-1, GAT-3 and GABAR α1 subunit were all significantly increased in TRMs hippocampus by real time PCR and Western blot, respectively; GAT-1 and GABAR α1 subunit proteins were localized widely in TRMs and control rats hippocampus including CA1, CA3 and dentate gyrus (DG) regions whereas only a wide distribution of GAT-3 was observed in CA1 region by immunohistochemistry. These data demonstrate that excessive expressions of GAT-1 as well as GAT-3 and GABAR α1 subunit in TRMs hippocampus may provide the potential therapeutic targets for genetic epilepsy. [Copyright &y& Elsevier]

Abstract: Excessive glutamatergic neurotransmission is considered an underlying factor of epilepsy. The modulation of the synaptic activity occurs both by the removal of glutamate from the synaptic cleft and by excitatory amino acid transporters (EAATs) and by modulation of glutamate receptors. The spontaneously epileptic rat (SER), a double mutant (zi/zi, tm/tm), exhibits both tonic convulsions and absence-like seizures from the age of 8 weeks. However, there are no reports that can elucidate the effects of EAATs and metabotropic glutamate receptors (mGluRs) in SER. The present study was undertaken to detect EAATs (GLAST, GLT-1 and EAAC-1) and Group I metabotropic glutamate receptors (mGluR1) in SER hippocampus from both the level of mRNA and protein in SERs hippocampus compared with control Wistar rats. In this study, the glutamate concentration in SERs hippocampus was increased compared with that of control rats by high performance liquid chromatography; the mRNA expressions of GLAST and mGluR1 in SERs hippocampus were significantly lower than those in control rats hippocampus, whereas an abundant increase in mRNA for GLT-1 was observed by RT-PCR; EAAC-1 and mGluR1 protein in SERs and control rats were localized widely in the hippocampus including CA1, CA3 and dentate gyrus regions by immunohistochemistry; the number of GLAST and mGluR1-positive cells in the hippocampus of SERs were less than those in control rats, especially for CA3 and DG region; the protein expression of GLT-1 was up-regulated, but the protein expressions of GLAST and mGluR1 were down-regulated in SER hippocampus by western blot. Our data show that epileptogenesis in SER are associated with regulations of glutamate transporters and mGluR1, which might be potential targets for therapy in genetic epilepsy. [Copyright &y& Elsevier]

• 0D, 1D, 2D, and composite nanomaterials have been extensively explored for autoimmune inflammation treatment. • The therapeutic efficacy and related autoimmune pathogenesis are varied on the basis of nanomaterials. • Future research should combine the merits of nanomaterials with new therapeutic modalities. Nanomaterials are playing an advancing critical role in the prevention, diagnosis, and treatment of today's human problems. By engineering with multi-active probes including biocompatible molecules, drugs, and target ligands, nanomaterials are able to inhibit or enhance the immune responses and prevent the detection ability of the immune system, thus treating autoimmune diseases. The present discussion systematically reviews the recent progress to treat autoimmune inflammation using nanomaterials of 0D, 1D, 2D, and composite systems. In addition, emphasis has laid on the using of nanomaterials-based immunotherapeutic strategies and the related autoimmune pathogenesis. Briefly discussions on current challenges and speculates on future directions have been provided to complement our drawbacks of present treatments on the basis of fascinating nanomaterials and novel nanotechnologies. [ABSTRACT FROM AUTHOR]

Circulating tumor cell (CTC) clusters, which are multicellular groups of CTCs, were recently suggested to had the greater potential of forming distal metastasis than single CTCs. However, our understanding of the forming of CTC clusters is still limited since there are few existing methods to study cancer cells aggregation kinetics, especially for a small number of cells. Herein we report a high-throughput miniaturized microwell-based cell aggregation-chip (AG-chip) to enable better characterize of the tumor cells clustering process. We successfully demonstrated the capability of the AG-chip in determining cell aggregation, and found that: (1) high metastatic breast cancer cells (MDA-MB-231 & MDA-MB-436) have stronger aggregation capacities than those low metastatic breast cancer cells (MCF-7 & SK-BR-3); (2) cells with similar aggregation ability were distinguished through the analysis of aggregation kinetics; (3) the detected aggregation ability can be used to indicate the metastatic potential of the cells; (4) the inhibition of integrins could regulate the cell clustering via blockage of cell adhesion or/and cell migration. This newly developed microdevice may promote further study of CTC clusters and metastasis. Image 1 • The cell aggregation of a small number of cells was detected in the microsystem. • The aggregation kinetic was analyzed by the moving path of individual cells. • The measured aggregation capacity could indicate the metastatic potential. • Integrins are found to be associated with aggregation capacity of cells. [ABSTRACT FROM AUTHOR]

We developed a new strategy to restrict the motions of AIE molecules through host–guest inclusion, affording a catalogue of new molecular luminogens. [ABSTRACT FROM AUTHOR]

Highlights: A comprehensive review of the recent development of two-dimensional (2D) PtSe2 synthesis strategies has been extensively surveyed. The applications of 2D PtSe2 materials in areas, including opto/electric devices, photocatalysis, hydrogen evolution reaction, and sensors, have been reviewed. Current challenges in the development of 2D PtSe2 materials are identified, and outlooks toward unexplored research areas are suggested. In recent years, emerging two-dimensional (2D) platinum diselenide (PtSe2) has quickly attracted the attention of the research community due to its novel physical and chemical properties. For the past few years, increasing research achievements on 2D PtSe2 have been reported toward the fundamental science and various potential applications of PtSe2. In this review, the properties and structure characteristics of 2D PtSe2 are discussed at first. Then, the recent advances in synthesis of PtSe2 as well as their applications are reviewed. At last, potential perspectives in exploring the application of 2D PtSe2 are reviewed. [ABSTRACT FROM AUTHOR]

• Highlight the emerging 2D material based nanocarriers for biomedical applications. • Summarized surface engineering strategy used in nanocarriers. • Overview the biomedical application of 2D material nanocarriers. • Give a guide to design stimuli-responsive controllable drug release strategy. • Proposed insightful prospects for the future development of 2D material based nanocarriers application. 2D materials (e.g., graphene, graphene analogues), with unique physical and chemical properties, shows intriguing potential for the realization of versatile biomedical applications. Tremendous attention has been attracted on 2D material based nanocarriers, which play a crucial role in therapeutic drug, gene, and biomedical agent delivery for cancer theranostics. This review provides an up-to-date review on the development of nanocarriers based on 2D materials beyond graphene, including basic and emerging synthesis methods, the catalog of 2D material-based nanocarriers, biosafety, surface functional engineering, the realization of stimuli-responsive controllable release and biomedical applications. Among the properties and performance to be summarized, there is particular focus on nanocarriers loading capability, biosafety, and therapy efficiency and so on. Finally, by addressing major issues and challenges, some prospects for future directions in this area are provided. [ABSTRACT FROM AUTHOR]

Phosphorene as a rising star is a monolayer or few‐layer form of black phosphorus (BP), which is used as a 2D material, in addition to graphene. This monoelemental 2D material has gained considerable attention in the fields of electronics, optoelectronics, and biomedicine due to its extraordinary physical properties. However, as both theoretical and experimental works show, the intrinsic instability of phosphorene under ambient conditions is a major challenge in practical applications. Various theoretical and experimental researches regarding the mechanism of the degradation and passivation strategies are proposed and reported to overcome the problem of the ambient instability of phosphorene. These strategies have enabled researchers to conduct fundamental studies on phosphorene's extraordinary properties. Here, not only an extensive summary of these passivation strategies but also an overview of the fabrication methods, challenges, and suitable applications of phosphorene are provided. [ABSTRACT FROM AUTHOR]

Accurate and timely diagnosis of transplant rejection is essential for the long‐term survival of solid‐organ transplant recipients. Biopsy is the "gold standard" for the diagnosis of rejection, but this approach is a time‐consuming, expensive, and invasive process. An efficient, cheap, and noninvasive tool for monitoring of immune rejection is urgently needed. Circulating miRNA and circulating DNA can be easily amplified and quantified by PCR which could be potential biomarkers for monitoring organ survival and/or immune rejection. In this review, we briefly introduce the origins and characteristics of circulating miRNA and circulating DNA. Furthermore, we review their clinical application and potential as noninvasive biomarkers for rejection in organ transplantation. Finally, we sum up their potential as biomarkers, which may help scientists and surgeons choose the proper biomarker for routine assays. [ABSTRACT FROM AUTHOR]