Checkerboard arranged G4 nanostructure-supported electrochemical platform and its application to unique bio-enzymes examination.

In this study, a checkerboard arranged G4 nanostructure-supported electrochemical platform is developed well for the application to unique bio-enzymes examination. Herein, we focus on the two bio-enzymes involving histone acetyltransferase (HAT) and terminal deoxynucleotidyl transferase (TdT); the former leads to the acetyl transfer of acetyl coenzyme A to the lysine residue of the substrate peptide and the latter achieves the polymeric extension of DNA without template under a unique pool of dATP and dGTP (4: 6). A complex of antibody and short DNA is introduced onto the electrode surface based on the affinity interaction between acetyl in acetylated peptide and its antibody. and used for initiating reaction. Then, TdT-yielded rich-G sequence is formed to act as the backbone of checkerboard, and subsequently free G-DNAs can be stacked continually on the backbone under Mg2+. An excellent electrocatalytic signal to H2O2 emerges noticeably, which is related with the activity of HAT p300 and TdT with a low detection limit of 2.3 pM and 0.38 mU/mL, respectively. Finally, this strategy is also used successfully for the inhibitor screening and complex sample analysis, which has important implications for the advancement of HAT- and TdT-related electrochemical bioassay and drug discovery.

Development of ZnO nanoflowers-assisted DNAzyme-based electrochemical platform for invertase and glucose oxidase-dominated biosensing.

The investigation on invertase (INV) and glucose oxidase (GOx)-dominated biological process offers a new opportunity for the development of clinical diagnosis and prognostic treatment. Herein, a ZnO nanoflowers (ZnONFs)-assisted DNAzyme-based electrochemical platform for INV- and GOx-dominated biosensing is proposed by the change of pH in microenvironment. In this strategy, INV can usually catalyze the dissolution of sucrose to generate glucose, and glucose is then consumed by GOx to produce H2O2 and gluconic acid, in which ZnONFs can be effectively etched into free Zn2+ ions. Subsequently, the released Zn2+ ions have a shearing action for Zn2+-specific DNAzyme, thus triggering hybridization chain reaction along with the imbedding of methylene blue. The excellent electrochemical signals illustrate the method can be employed well for testing sucrose, INV and GOx with a low detection limit (0.019 µM, 0.047 mU/mL and 0.012 mU/mL, respectively). Finally, a series of basic and advanced logic gates (YES, AND, INHIBIT, and AND-AND-INHIBIT) in the biological process are constructed with different logic inputs, providing a valuable platform for the establishment of advanced molecular devices for bioanalysis and clinical diagnostics.

Supramolecular Host-Guest Interaction-Driven Electrochemical Recognition for Pyrophosphate and Alkaline Phosphatase Analysis.

We report an electrochemical biosensor based on the supramolecular host-guest recognition between cucurbit[7]uril (CB[7]) and L-phenylalanine-Cu(II) complex for pyrophosphate (PPi) and alkaline phosphatase (ALP) analysis. First, L-Phe-Cu(II) complex is simply synthesized by the complexation of Cu(II) (metal node) with L-Phe (bioorganic ligand), which can be immobilized onto CB[7] modified electrode via host-guest interaction of CB[7] and L-Phe. In this process, the signal of the complex-triggered electro-catalytic reduction of H2 O2 can be captured. Next, due to the strong chelation between PPi and Cu(II), a biosensing system of the model "PPi and Cu(II) premixing, then adding L-Phe" was designed and the platform was applied to PPi analysis by hampering the formation of L-Phe-Cu(II) complex. Along with ALP introduction, PPi can be hydrolyzed to orthophosphate (Pi), where abundant Cu(II) ions are released to form L-Phe-Cu(II) complex, which gives rise to the catalytic reaction of complex to H2 O2 reduction. The quantitative analysis of H2 O2 , PPi and ALP activity was achieved successfully and the detection of limits are 0.067 µM, 0.42 µM and 0.09 mU/mL (S/N=3), respectively. With its high sensitivity and selectivity, cost-effectiveness, and simplicity, our analytical system has great potential to for use in diagnosis and treatment of ALP-related diseases.

Cascade i-motifs-dependent reversibleelectrochemical impedance strategy-oriented pH and terminal deoxynucleotidyl transferase biosensing.

In this study, we develop a novel and reversibleelectrochemical impedance strategy for pH and terminal deoxynucleotide transferase (TdT) analysis based on the TdT-assisted generation of long enough cytosine (C)-rich DNAs. The formation of this special DNA is rationally designed on 5'-thiol DNA modified Au electrode surface, and TdT can catalyze the extension of this 3'-OH end to form a long C-rich DNA in the presence of deoxycytidine triphosphate (dCTP). Here, we discover a reversible process, in which the TdT-generated C-rich DNA maintains an irregular single chain state under neutral conditions and some stable DNA i-motifs (cascade i-motifs) are formed due to the partial protonation of C under acidic conditions. More importantly, the electrochemical impedance spectroscopy (EIS) response varies with the configuration change of the TdT-mediated C-rich DNA under different pH conditions. In view of this, a unique EIS switch ("on-off-on") is constructed faithfully with the configuration change, thus achieving pH analysis well. Additionally, the TdT activity can be also detected well by recording the EIS response, because it can catalyze the DNA tailing process up to hundreds of cytosines; on the contrary, if its inhibitor exists, TdT-based extension and formation of cascade i-motifs will not occur. Using this strategy, the detection of limit for TdT is 0.79 × 10-5 U/mL (pH 7.0) and 0.25 × 10-5 U/mL (pH 5.8) (S/N = 3), respectively. All the above features make our biosensor a promising assay for in situ monitoring of pH and TdT in complex clinical diagnosis.

Peri-tumoral brain edema associated with glioblastoma correlates with tumor recurrence.

Glioblastoma is the most common malignant tumor of the brain. Despite advances in treatment, the prognosis for the condition has remained poor. Glioblastoma is often associated with peritumoral brain edema (PTBE), which can result in increased intracranial pressure and devastating neurological sequelae if left untreated. Surgery is the main treatment for glioblastoma, however current international surgical guidelines do not specify whether glioblastoma-induced PTBE tissue should be resected. In this study, we analyzed treatment outcomes of PTBE using surgical resection. We performed a retrospective analysis of 255 cases of glioblastoma between 2014 and 2016, and found that a significant proportion of patients had a degree of PTBE. We found that surgical resection led to reduction in midline shift that had resulted from edema, however, postoperative complications and KPS scores were not significantly different in the two conditions. We also observed a delay in glioblastoma recurrence in patients undergoing PTBE tissue resection vs patients without resection of PTBE tissue. Interestingly, there was an abnormal expression of tumor associated genes in PTBE, which has not been previously been found. Taken together, this study indicates that glioblastoma-induced PTBE should be investigated further particularly as the tumor microenvironment is a known therapeutic target and therefore interactions between the microenvironment and PTBE should be explored. This study also highlights the importance of resection of PTBE tissue to not only reduce the mechanical obstruction associated with edema but also to delay recurrence of glioblastoma.

Adaptive Immunity Regulation and Cerebral Ischemia.

Stroke is a disease that occurs due to a sudden interruption of the blood supply to the brain. It is a leading cause of death and disability worldwide. It is well-known that the immune system drives brain injury following an episode of ischemic stroke. The innate system and the adaptive system play distinct but synergistic roles following ischemia. The innate system can be activated by damage-associated molecular patterns (DAMPs), which are released from cells in the ischemic region. Damaged cells also release various other mediators that serve to increase inflammation and compromise the integrity of the blood-brain barrier (BBB). Within 24 h of an ischemic insult, the adaptive immune system is activated. This involves T cell and B cell-mediated inflammatory and humoral effects. These cells also stimulate the release of various interleukins and cytokines, which can modulate the inflammatory response. The adaptive immune system has been shown to contribute to a state of immunodepression following an ischemic episode, and this can increase the risk of infections. However, this phenomenon is equally important in preventing autoimmunity of the body to brain antigens that are released into the peripheral system as a result of BBB compromise. In this review, we highlight the key components of the adaptive immune system that are activated following cerebral ischemia.

Dumbbell shaped craniorbital cavernous hemangioma.

BACKGROUND: Cavernous hemangioma of the orbit is a benign tumor mostly located behind the eye globe, but it rarely spread into the brain, which is called cerebral cavernous malformation as well, the lesion in the brain is irregular and enlarged blood. Here we report one particular case of craniorbital cavernous hemangioma. CASE PRESENTATION: A 53-year-old woman presented with exophthalmos of the right eye and reduced vision. Computerized tomographical (CT) scan showed osteolytic honeycomb radial changes of the outer plate of the skull. A magnetic resonance imaging (MRI) scan was performed to obtain further details. T1-weighted (T1W) imaging showed slightly low signal mixed with small patchy high signal. T2-weighted (T2W) imaging showed uneven high signal. There was obvious enhancement in the middle and no enhancement in the peripheral bars. A surgically manage was performed using a left frontotemporal approach, the tumor excised fully, and the histopathology results revealed a cavernous hemangioma. The patient recovered well in the follow-up. Post-operative CT scan identified the lesion was successfully resected, MRI scan also showed full resection and enhanced signal from the presence of fat. CONCLUSIONS: Craniorbital cavernous hemangioma is uncommon, however within the cranium, they can lead to numerous complications particularly if affecting the visual apparatus. it could be diagnosed by imaging, which CT scan shows osteolytic honeycomb radial changes of the outer plate of the skull, T1W imaging shows slightly low signal mixed with small patchy high signal, T2W imaging shows uneven high signal, it is obvious enhancement in the middle and no enhancement in the peripheral bars. The surgically manage is the ideally treatment when there are some symptoms.

MicroRNA-26b/PTEN Signaling Pathway Mediates Glycine-Induced Neuroprotection in SAH Injury.

Subarachnoid hemorrhage (SAH) is a form of stroke associated with high mortality and morbidity. Despite advances in treatment for SAH, the prognosis remains poor. We have previously demonstrated that glycine, a non-essential amino acid is involved in neuroprotection following intracerebral hemorrhage via the Phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) signaling pathway. However, whether it has a role in inducing neuroprotection in SAH is not known. The present study was designed to investigate the role of glycine in SAH. In this study, we show that glycine can reduce brain edema and protect neurons in SAH via a novel pathway. Following a hemorrhagic episode, there is evidence of downregulation of S473 phosphorylation of AKT (p-AKT), and this can be reversed with glycine treatment. We also found that administration of glycine can reduce neuronal cell death in SAH by activating the AKT pathway. Glycine was shown to upregulate miRNA-26b, which led to PTEN downregulation followed by AKT activation, resulting in inhibition of neuronal death. Inhibition of miRNA-26b, PTEN or AKT activation suppressed the neuroprotective effects of glycine. Glycine treatment also suppressed SAH-induced M1 microglial polarization and thereby inflammation. Taken together, we conclude that glycine has neuroprotective effects in SAH and is mediated by the miRNA-26b/PTEN/AKT signaling pathway, which may be a therapeutic target for treatment of SAH injury.

Mechanism and Treatment Related to Oxidative Stress in Neonatal Hypoxic-Ischemic Encephalopathy.

Hypoxic ischemic encephalopathy (HIE) is a type of neonatal brain injury, which occurs due to lack of supply and oxygen deprivation to the brain. It is associated with a high morbidity and mortality rate. There are several therapeutic strategies that can be used to improve outcomes in patients with HIE. These include cell therapies such as marrow mesenchymal stem cells (MSCs) and umbilical cord blood stem cells (UCBCs), which are being incorporated into the new protocols for the prevention of ischemic brain damage. The focus of this review is to discuss the mechanism of oxidative stress in HIE and summarize the current available treatments for HIE. We hope that a better understanding of the relationship between oxidative stress and HIE will provide new insights on the potential therapy of this devastating condition.