A Highly Selective Fluorescent Probe for Imaging Hydrogen Sulfide in Living HeLa Cells.

As an important endogenous gasotransmitter, hydrogen sulfide (H2S) has been implicated with a variety of biological processes and has attracted more and more attention for its key role in a wide range of pathological processes. However, lacking tools for H2S-specific in situ detection, the changes of endogenous H2S levels in the pathological progression of diseases are still unclear. In this work, a turn-on fluorescent probe (BF2-DBS) has been designed and synthesized by two-step reactions using 4-diethylaminosalicylaldehyde and 1,4-dimethylpyridinium iodide as raw materials. Probe BF2-DBS displays high selectivity and sensitivity to H2S with a large Stokes shift and good anti-interference ability. The practical application of probe BF2-DBS to detect endogenous H2S was evaluated in living HeLa cells.

Attenuated succinate accumulation relieves neuronal injury induced by hypoxia in neonatal mice.

Hypoxia causes neonatal neuronal damage. However, the underlying mechanism remains unclear. This study aimed to explore the changes in succinate levels and identify the mechanisms underlying their contribution to hypoxia-induced damage in newborn mice. The neonatal C57BL/6J mouse hypoxia model was used in our study. We evaluated the levels of succinate, iron, reactive oxygen species (ROS), and mitochondrial ROS, and assessed mitophagy, neuronal damage, and learning and memory function, after hypoxia treatment. The neonatal mice showed increased succinate levels in the early hypoxia stage, followed by increased levels of oxidative stress, iron stress, neuronal damage, and cognitive deficits. Succinate levels were significantly reduced following treatment with inhibitors of succinate dehydrogenase (SDH), purine nucleotide cycle (PNC), and malate/aspartate shuttle (MAS), with the corresponding attenuation of oxidative stress, iron stress, neuronal damage, and cognitive impairment. Reversal catalysis of SDH through fumarate from the PNC and MAS pathways might be involved in hypoxia-induced succinate accumulation. Succinate accumulation in the early period after hypoxia may crucially contribute to oxidative and iron stress. Relieving succinate accumulation at the early hypoxia stage could prevent neuronal damage and cognitive impairment in neonatal hypoxia.

Anti-Seizure and Neuronal Protective Effects of Irisin in Kainic Acid-Induced Chronic Epilepsy Model with Spontaneous Seizures.

An increased level of reactive oxygen species is a key factor in neuronal apoptosis and epileptic seizures. Irisin reportedly attenuates the apoptosis and injury induced by oxidative stress. Therefore, we evaluated the effects of exogenous irisin in a kainic acid (KA)-induced chronic spontaneous epilepsy rat model. The results indicated that exogenous irisin significantly attenuated the KA-induced neuronal injury, learning and memory defects, and seizures. Irisin treatment also increased the levels of brain-derived neurotrophic factor (BDNF) and uncoupling protein 2 (UCP2), which were initially reduced following KA administration. Furthermore, the specific inhibitor of UCP2 (genipin) was administered to evaluate the possible protective mechanism of irisin. The reduced apoptosis, neurodegeneration, and spontaneous seizures in rats treated with irisin were significantly reversed by genipin administration. Our findings indicated that neuronal injury in KA-induced chronic epilepsy might be related to reduced levels of BDNF and UCP2. Moreover, our results confirmed the inhibition of neuronal injury and epileptic seizures by exogenous irisin. The protective effects of irisin may be mediated through the BDNF-mediated UCP2 level. Our results thus highlight irisin as a valuable therapeutic strategy against neuronal injury and epileptic seizures.

Dibromidobis{1-[4-(pyridin-4-yl)phen-yl]ethanone-κN}mercury(II).

In the title compound, [HgBr(2)(C(13)H(11)NO)(2)], the Hg(II) atom adopts a four-coordinated HgN(2)Br(2) geometry, formed by two pyridine N atoms from two ligands and two bromide anions. The complex is located on a twofold axis. The coordination geometry is close to forming a see-saw (SS-4) polyhedron, the symmetry-related organic ligands being almost perpendicular; the dihedral angles between the two pyridine rings and between the two benzene rings are 85.5 (4) and 87.7 (4)°, respectively. Within the organic ligand, the pyridine ring is nearly coplanar with the benzene ring [dihedral angle = 13.1 (8)°]. In the crystal, the mol-ecular complexes are connected through weak inter-molecular C-H⋯Br contacts.

Cu2+-selective naked-eye and fluorescent probe: its crystal structure and application in bioimaging.

A new fluorescent and colorimetric Cu2+ probe was synthesized, and realized optical imaging in RAW264.7 macrophages. The design strategy was based on a change in structure between spirocyclic (non-fluorescent) and ring-open (fluorescent) forms of rhodamine-based dyes, and its crystal structure was presented to explain the binding mode. Upon treatment with Cu2+, the weakly fluorescent probe exhibited a strong fluorescence response, high selectivity and was quantitative for Cu2+ under physiological conditions. In addition, the off-on-type fluorescent change upon the addition of Cu2+ was also applied in bioimaging.

A highly sensitive acidic pH fluorescent probe and its application to HepG2 cells.

A novel acidic fluorescent probe 1 has been designed, synthesized, characterized and evaluated in vivo as optical imaging of intracellular H(+). The design strategy for the probe is based on the change in structure between spirocyclic (non-fluorescent) and ring-open (fluorescent) forms of rhodamine dyes. The probe exhibits high sensitivity, good photostability, excellent cell membrane permeability and strong pH dependence. The pH titration indicates that the fluorescence intensity increases more than 100-fold within the pH range of 4.2-6.0 with the pK(a) value of 4.85, which is valuable for studying acidic organelles in living cells. The fluorescent imaging of HepG2 cells also demonstrates that the designed probe has great value in monitoring intracellular H(+) within living cells.

Is amyloid binding alcohol dehydrogenase a drug target for treating Alzheimer's disease?

Current strategies for the treatment of Alzheimer's disease (AD) involve tackling the formation or clearance of the amyloid-beta peptide (Aß) and/or hyper-phosphorylated tau, or the support and stabilization of the remaining neuronal networks. However, as we gain a clearer idea of the large number of molecular mechanisms at work in this disease, it is becoming clearer that the treatment of AD should take a combined approach of dealing with several aspects of the pathology. The concept that we also need to protect specific sensitive targets within the cell should also be considered. In particular the role of protecting the function of a specific mitochondrial protein, amyloid binding alcohol dehydrogenase (ABAD), will be the focus of this review. Mitochondrial dysfunction is a well-recognized fact in the progression of AD, though until recently the mechanisms involved could only be loosely labeled as changes in 'metabolism'. The discovery that Aß can be present within the mitochondria and specifically bind to ABAD, has opened up a new area of AD research. Here we review the evidence that the prevention of Aß binding to ABAD is a drug target for the treatment of AD.