Water-soluble dual lysosome/mitochondria-targeted fluorescent probe for detection of SO2 in water, food, herb, and live cells.

In this paper, we present a new donor-π bridge-acceptor type fluorescent probe, MIB, which bears two organelle-targeted groups, namely positively charged benzothiazole group for mitochondria and morpholine moiety for lysosomes. In aqueous solution, the nucleophilic addition of HSO3- (as SO2 donor) to MIB blocked its long-range π-conjugation and ICT process and resulted in significant optical signal changes (blue-shifted UV absorbance and fluorescence), which enabled colorimetric and ratiometric fluorescent detection of HSO3- with high selectivity and sensitivity (detection limit of 63.15 nM). MIB offers obvious advantages of good water-solubility, fast response time (within 1 min), unique dual lysosome/mitochondria targeting capability and has been applied to the sensing of endogenous and exogenous SO2 in live cells through fluorescent imaging. In addition, the proposed probe has been utilized for the determination of bisulfite in real water, food and herbal medicine samples, showing good recovery (91.45 % - 109.3 %) and precision.

Melatonin Attenuates Cardiac Reperfusion Stress by Improving OPA1-Related Mitochondrial Fusion in a Yap-Hippo Pathway-Dependent Manner.

The role of OPA1-related mitochondrial fusion in cardiac reperfusion stress has remained elusive. The aim of our study is to explore whether melatonin alleviates cardiac ischemia-reperfusion (IR) injury by modulating OPA1-related mitochondrial fusion. We found that melatonin reduced infarct area, sustained myocardial function, and suppressed cardiomyocyte death during cardiac reperfusion stress. Biological studies have revealed that IR-inhibited mitochondrial fusion was largely reversed by melatonin through upregulated OPA1 expression. Knocking down OPA1 abrogated the protective effects of melatonin on mitochondrial energy metabolism and mitochondrial apoptosis. In addition, we also found that melatonin modified OPA1 expression through the Yap-Hippo pathway; blockade of the Yap-Hippo pathway induced cardiomyocyte death and mitochondrial damage despite treatment with melatonin. Altogether, our data demonstrated that cardiac IR injury is closely associated with defective OPA1-related mitochondrial fusion. Melatonin supplementation enhances OPA1-related mitochondrial fusion by activating the Yap-Hippo pathway, ultimately reducing cardiac reperfusion stress.

The anti-apoptotic effect of nerve growth factor on propofol-induced neurotoxicity in hippocampal neurons is Rac1 dependent.

Propofol has been considered as a near-ideal anesthetic agent since its introduction 40 years ago. However, the side effects of propofol including bacterial contamination, hyperlipidemia, and neurotoxicity also aroused attention. Nerve growth factor (NGF) plays a pivotal role in the development, differentiation, and survival of the neurons of the peripheral and central nervous system. In the present study, we found that NGF alleviated the apoptosis induced by propofol in hippocampal neurons. Furthermore, NGF treatment augmented the protein abundance and mRNA level of Rac1 while silencing Rac1 significantly blunted the effects of NGF upon propofol-induced apoptosis. In conclusion, NGF decreased propofol-induced apoptosis and this effect was Rac1 dependent.

Dexmedetomidine mitigates sevoflurane-induced cell cycle arrest in hippocampus.

BACKGROUND: Epidemiologic studies suggest the possibility of a modestly elevated risk of adverse neurodevelopmental outcomes in children exposed to anesthesia during early childhood. Sevoflurane is widely used in pediatric anesthetic practice because of its rapid induction and lower pungency. However, it is reported that sevoflurane leads to the long-term cognitive impairment. Some evidence revealed that the selective α2-adrenoreceptor agonist dexmedetomidine (DEX) exerts neuroprotective effects in various brain injury models of animals. But the role of DEX on sevoflurane-induced neuro-damage remains elusive. MATERIALS AND METHODS: In our study, we isolated the hippocampal neuron cells from newborn neonatal rats and verified the purity of neurons by immunocytochemistry. We employed the flow cytometry and western blot to examine the effect of sevoflurane, DEX and α2-adrenergic receptor antagonist yohimbine on cell cycle distribution. RESULTS: Immunocytochemistry results showed the purity of neurons > 94%, which provided a good model for neural pharmacology experiments. The exposure of sevoflurane-induced cell cycle arrest at S phase and suppressed the expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB). The addition of DEX suppressed sevoflurane-induced cell cycle arrest and the inhibitory of BDNF and TrkB expression. But the function of DEX was partly blocked by a α2 adrenergic receptor blocker yohimbine. CONCLUSION: Sevoflurane suppressed neuron cell proliferation via inhibiting the expression of BDNF and TrkB, and DEX relieved the neurotoxicity induced by sevoflurane via α2 adrenergic receptor. These findings provided new evidence that DEX exerted as a neuroprotective strategy in sevoflurane-induced neuro-damage, and provided new basis for the clinical application of DEX.

A sensitive "turn-on" Schiff-base fluorescent probe for the selective detection of Fe3+ and bio-imaging.

A novel Schiff-base fluorescent probe, 4-(N-(2- hydroxyl-1-naphthalymethylimino)-ethylamino) -7-nitro-1,2,3-benzoxadiazole (HENB) was synthesized and utilized for spectral sensing of Fe3+ ions at neutral pH. The binding of Fe3+ to HENB in C2H5OH-HEPES buffer (1:1 v/ v, 25 mM, pH 7.2) resulted in a pronounced emission enhancement at 530 nm, which is possibly due to the inhibition of photo-induced electron transfer (PET) process as well as the chelation enhanced fluorescence (CHEF) effect. HENB shows good selectivity and sensitivity toward Fe3+ with the detection limit as low as 4.51 nM. Test strips made of HENB was used for rapid "naked-eye" detection of Fe3+ ions in aqueous medium. Moreover, HENB was successfully applied in fluorescence imaging of exogenous and endogenous Fe3+ in live Hela cells as well as zebrafish. Importantly, HENB is capable of effectively monitoring the variations of Fe3+ in living cells during ferroptosis process.

Bis(10-meth-oxy-benzo[h]quinolinium) tetra-chloridozinc.

In the title compound, (C(14)H(12)NO)(2)[ZnCl(4)], the benzo[h]quinolinium groups are approximately planar, with maximum deviations of 0.049 (8) and 0.056 (9) Å. The meth-oxy groups are stabilized by intra-molecular N-H⋯O hydrogen bonds. The structure also exhibits weak inter-molecular N-H⋯Cl hydrogen bonds between the cations and anions. π-π inter-actions are present between the pyridinium and benzene rings [centroid-centroid distances = 3.640 (4), 3.728 (5) and 3.628 (5) Å].

2-(Anthracen-9-yl)-10-meth-oxy-benzo[h]quinoline acetone hemisolvate.

The asymmetric unit of the title structure, C(28)H(19)NO·0.5C(3)H(6)O, comprises one 2-(anthracen-9-yl)-10-meth-oxy-benzo[h]-quinoline mol-ecule and an acteone mol-ecule with an occupany of 0.5. The solvent mol-ecule is disordered around a centre of symmetry. Its occupancy was determined from NMR data and kept fixed during the refinement. The two conjugated ring systems of the mol-ecule are almost perpendicular to each other; the inter-planar angle between the anthracene and quinoline ring systems is 84.9 (2)°.

Selective visualization of cyanide in food, living cells and zebrafish by a mitochondria targeted NIR-emitting fluorescent probe.

Cyanide is a highly toxic substance, and the detection of cyanide in the environment and food samples is critical to public health care. Herein, we rationally designed a mitochondria-targeted near-infrared fluorescent probe BTC for ratiometric monitoring of CN- in water, food, living cells, and zebrafish. BTC exhibits a remarkable colorimetric ratiometric fluorescence response to CN- with high selectivity, low detection limit (54.3 nM), and large Stokes shift. The cyanide sensing mechanism was demonstrated by NMR and ESI-MS analysis and density functional theory (DFT). More importantly, BTC was used for efficient naked-eye colorimetric detection of CN- in sprouting potatoes, almonds, and ginkgo fruit samples. Further, the BTC is capable of situ tracking and imaging cyanide in mitochondria of SMMC-7721 cells and in zebrafish via dual emission channels, and was prepared into a kit for convenient and visual on-site sensing of cyanide in food samples.

A polarization-based image restoration method for both haze and underwater scattering environment.

Existing polarization-based defogging algorithms rely on the polarization degree or polarization angle and are not effective enough in scenes with little polarized light. In this article, a method of image restoration for both haze and underwater scattering environment is proposed. It bases on the general assumption that gray variance and average gradient of a clear image are larger than those of an image in a scattering medium. Firstly, based on the assumption, polarimetric images with the maximum variance (Ibest) and minimum variance (Iworst) are calculated from the captured four polarization images. Secondly, the transmittance is estimated and used to remove the scattering light from background medium of Ibest and Iworst. Thirdly, two images are fused to form a clear image and the color is also restored. Experimental results show that the proposed method obtains clear restored images both in haze and underwater scattering media. Because it does not rely on the polarization degree or polarization angle, it is more universal and suitable for scenes with little polarized light.

Reduction of nitroarenes to azoxybenzenes by potassium borohydride in water.

The synthesis of the azoxybenzenes by the reduction of nitroarenes with reducing agent potassium borohydride in water was reported for the first time. PEG-400 was used as a phase transfer catalyst and could effectively catalyze the reduction. The electronic effects of substituent groups play an important role in determining the reduction efficiencies. Electron-withdrawing substituents promote the formation of the azoxybenzene products, while electron-releasing groups retard the reductions to various degrees depending on the extent of their electron-donating ability.

1,3,3-Tribenzyl-indolin-2-one.

In the title compound, C(29)H(25)NO, the dihedral angles between the indolin-2-one ring system and the three benzene rings are 62.78 (9), 31.69 (9) and 80.94 (9)°.

Protective effect of dexmedetomidine against myocardial ischemia-reperfusion injury in rabbits.

PURPOSE: To investigate the influence of dexmedetomidine on myocardial ischemia-reperfusion injury (IRI) in rabbits. METHODS: Twenty-four New Zealand white rabbits were randomly divided into two equal-sized groups: IRI group (group IR) and dexmedetomidine group (group D). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), left ventricular diastolic pressure (LVDP), +dp/dtmax, -dp/dtmax, and t-dp/dtmax were recorded and calculated at the following time points: before (T0) and after (T1) dexmedetomidine infusion, after 30-min ischemia (T2), and after 120-min reperfusion (T3). The levels of plasma endothelin 1 (ET-1), thromboxane A2 (TXA2), and platelet activating factor (PAF); area of myocardial infarction (MI); and no-reflow area were evaluated. RESULTS: SBP, DBP, LVSP, LVEDP, LVDP, and +dp/dtmax at T3 were higher in group D than in group IR (P<0.05). The average no-reflow area in group IR was significantly smaller than that in group D (14±3% vs. 38±5%, P=0.0116). The ET-1, TXA2, and PAF levels at T2 and T3 were higher than those at T0 in both groups (P<0.05). CONCLUSION: Dexmedetomidine could reduce the magnitude of ischemic myocardial no-reflow area and protect the myocardium with ischemia-reperfusion injury.

The protective effect of the Rho-kinase inhibitor hydroxyfasudil on propofol-induced hippocampal neuron apoptosis in neonatal rats.

Propofol is widely applied for anesthesia induction in pediatric patients. However, accumulating evidence has proved that propofol is neurotoxic to the immature or developing brain. In the present study, we found that hydroxyfasudil, a specific inhibitor of Rho kinase, alleviated the apoptotic neurodegeneration induced by propofol in the developing rat brain. A spatial probe test and Morris water maze test revealed that hydroxyfasudil showed a potential improvement of the tendency towards cognitive impairments induced by propofol. Mechanistically, hydroxyfasudil markedly ameliorated the activation of RhoA and the expression of Rock1, Rock2, Bak, Bax, and Bad induced by propofol and rescued the expression of Bcl2 suppressed by propofol. Our findings suggest that hydroxyfasudil may serve as an effective agent to reduce the propofol-induced neurotoxic effects in pediatric medical procedures.

Synthesis and photophysical properties of complexes of Be(II) and Zn(II) with 10-hydroxybenzo[h]quinoline ligand.

Two 10-hydroxybenzo[h]quinoline metal complexes, bis(10-hydroxybenzo[h]quinolinato) beryllium (Bebq2) and bis(10-hydroxybenzo[h]quinolinato)zincum (Znbq2), have been synthesized. The structure are characterized by 1HNMR, IR and so on. The photophysical processes of Bebq2 and Znbq2 have been carefully investigated by fluorescence spectra. The results show that the compounds emit yellow-green and yellow light. The emission peaks are at 492 and 512 nm, respectively. In addition, the light-emitting can be quenched by electron donor, N,N-dimethylaniline (DMA), and the quenching process follows the Stern-Volmer equation. Furthermore, the molecular interactions of Bebq2 and Znbq2 with electron acceptor, dimethylterephthalate (DMTP), were also carefully investigated. It displayed that the Znbq2 is a potential substitute for Bebq2 as an excellent emitting material.

[Indirect determination of Vc with flame atomic absorption spectrometry].

In the present paper, a new method for indirect determination of Vc by atomic absorption spectrometry is proposed, based on the reducing properties of Ag+. The effects of temperature, reaction time and use level of Ag+ on the experiment were studied. Room-temperature and reaction time of 35 minutes were chosen. The oxidant amount is 2.0 mL solution of Ag+ (1.0 microg mL(-1)). Meanwhile the AAS working conditions for Ag determination were optimized. The proposed method allows the determination of Vc in a wide range with a relative standard deviation of 2.04%, and the detection limit is less than 1 microg x mL(-1). The method cannot be disturbed by the colour of sample. The interference of coexistent substance is also weak. Other methods for determining Vc could be remedied by this method. Two kinds of standard curves were plotted, standard working curve of sliver and standard working curve of Vc. The former is easier, while the latter is more accurate and could be applied flexibly according to the physical circumstances. This method is easy to control and has been applied to the determination of ascorbic acid in pharmaceutical preparations and orange juice. The recovery ratio of this method is 99.30%-106.06%. The results obtained in the analysis agreed well with the iodimetry in pharmacopeia.

Cerebral hemorrhage therapy by targeting VEGF and HGF in a preclinical trial in rats.

Cerebral hemorrhage is the most common type of human cerebrovascular disease and frequently causes paralysis, vegetative state and mortality. The modulatory actions of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are vital in the human nervous system. The present study investigated the association between cerebral hemorrhage and the expression of VEGF and HGF in a rat model of cerebral hemorrhage. The therapeutic potential of cerebral hemorrhage was also evaluated using targeted drugs for VEGF and HGF in the cerebral hemorrhage rat model. Behavioral and preclinical changes and the survival rates of rats were assessed after treatment with VEGF receptor (VEGFR) and HGF receptor (HGFR). The results of Tarlov scores demonstrated that movement of limbs and coordination when walking were significantly improved in moderate and severe hemorrhage lesions in the VEGFR plus HGFR­treated group and mainly alleviated in primary hemorrhage lesions compared with rats in the single VEGFR or HGFR­treated groups and the control group (**P<0.01). Decreasing expression levels of VEGF and HGF were observed in the neural tissue of animals treated with VEGFR plus HGFR compared with the control group (**P<0.01). These preclinical observations indicated that VEGF and HGF serve a function in the pathological injury and repair of cerebral tissue in rats with cerebral hemorrhages. The therapeutic benefits of VEGFR plus HGFR suggested that VEGFR plus HGFR may be candidate drugs for cerebral hemorrhage, and thus offer a promising treatment for clinicians and doctors.

Coumestrol inhibits carotid sinus baroreceptor activity by cAMP/PKA dependent nitric oxide release in anesthetized male rats.

Phytoestrogens could offer multiple beneficial effects on the cardiovascular system. Here, we have examined the effects of coumestrol (CMT) on carotid baroreceptors activity (CBA) and the possible mechanisms in male rats. The functional parameters of carotid baroreceptors were measured by recording sinus nerve afferent discharge in anesthetized male rats with perfused isolated carotid sinus. The levels of protein expression were determined by using ELISA and Western blotting. CMT (1 to 100µmolL(-1)) inhibited CBA, which shifted the functional curve of the carotid baroreceptor to the right and downward, with a marked decrease in the peak slope and the peak integral value of carotid sinus nerve discharge in a concentration dependent manner. These effects were not blocked by a specific estrogen receptor antagonist ICI 182,780, but were completely abolished by nitric oxide (NO) synthase inhibitor l-NAME (N(G)-nitro-l-arginine methyl ester). Furthermore, a NO donor, SIN-1(3-morpholion-sydnon-imine), could potentiate these inhibitory effects of CMT. CMT stimulated the phosphorylation of Ser(1176)-eNOS (endothelial nitric oxide synthase) in a dose-dependent manner in carotid bifurcation tissue over a perfusion period of 15min. The rapid activation of eNOS by CMT was blocked by a highly selective PKA (protein kinase A) inhibitor H89. In addition, inhibition of PI3K (phosphatidylinositol-3-kinase) and ERK (extracellular signal-regulated kinase) pathways had no effect on eNOS activation by CMT. CMT inhibited CBA via eNOS activation and NO synthesis. These effects were mediated by the cAMP/PKA pathway and were unrelated to the estrogenic effect.

Protective effect of dexmedetomidine against myocardial ischemia-reperfusion injury in rabbits

Abstract Purpose: To investigate the influence of dexmedetomidine on myocardial ischemia-reperfusion injury (IRI) in rabbits. Methods: Twenty-four New Zealand white rabbits were randomly divided into two equal-sized groups: IRI group (group IR) and dexmedetomidine group (group D). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), left ventricular diastolic pressure (LVDP), +dp/dtmax, -dp/dtmax, and t-dp/dtmax were recorded and calculated at the following time points: before (T0) and after (T1) dexmedetomidine infusion, after 30-min ischemia (T2), and after 120-min reperfusion (T3). The levels of plasma endothelin 1 (ET-1), thromboxane A2 (TXA2), and platelet activating factor (PAF); area of myocardial infarction (MI); and no-reflow area were evaluated. Results: SBP, DBP, LVSP, LVEDP, LVDP, and +dp/dtmax at T3 were higher in group D than in group IR (P<0.05). The average no-reflow area in group IR was significantly smaller than that in group D (14±3% vs. 38±5%, P=0.0116). The ET-1, TXA2, and PAF levels at T2 and T3 were higher than those at T0 in both groups (P<0.05). Conclusion: Dexmedetomidine could reduce the magnitude of ischemic myocardial no-reflow area and protect the myocardium with ischemia-reperfusion injury.

Protective effect of dexmedetomidine in coronary artery bypass grafting surgery.

The aim of this study was to observe the impact of dexmedetomidine on postoperative myocardial injury in patients undergoing off-pump coronary artery bypass (OPCAB) grafting. One hundred and sixty-two patients who were undergoing OPCAB surgery were randomly divided into control and dexmedetomidine groups (groups C and Dex, respectively). Following the first vascular anastomosis grafting, the patients in group Dex received a continuous intravenous infusion of 0.2-0.5 µg/kg/h dexmedetomidine, until they were transferred to the Cardiac Surgery intensive care unit (ICU) for 12 h. Patients in group C received physiological saline intraoperatively and an intravenous infusion of 2-4 mg/kg/h isopropylphenol for postoperative sedation. Invasive arterial pressure and heart rate were continuously monitored for 5 min subsequent to entry into the operating theatre (T0), immediately following surgery (T1), 12 h post-surgery (T2), 24 h post-surgery(T3), 48 h post-surgery(T4) and 72 h post-surgery (T5). Blood samples were taken to determine the plasma levels of cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) at each time point. At 72 h post-surgery, a dynamic electrocardiogram was monitored. The blood pressure, heart rate, levels of cTnI, CK-MB, norepinephrine and cortisol, and postoperative arrhythmic events in the patients in group Dex all decreased compared with those in group C. The duration of mechanical ventilation and ICU residence time were also shorter than those in the control group (P<0.05). Dexmedetomidine reduced post-surgical myocardial injury in patients who had undergone OPCAB surgery.

In vitro dose-dependent inhibition of the intracellular spontaneous calcium oscillations in developing hippocampal neurons by ketamine.

Spatial and temporal abnormalities in the frequency and amplitude of the cytosolic calcium oscillations can impact the normal physiological functions of neuronal cells. Recent studies have shown that ketamine can affect the growth and development and even induce the apoptotic death of neurons. This study used isolated developing hippocampal neurons as its study subjects to observe the effect of ketamine on the intracellular calcium oscillations in developing hippocampal neurons and to further explore its underlying mechanism using Fluo-4-loaded laser scanning confocal microscopy. Using a semi-quantitative method to analyze the spontaneous calcium oscillatory activities, a typical type of calcium oscillation was observed in developing hippocampal neurons. In addition, the administration of NMDA (N-Methyl-D-aspartate) at a concentration of 100 µM increased the calcium oscillation amplitude. The administration of MK801 at a concentration of 40 µM inhibited the amplitude and frequency of the calcium oscillations. Our results demonstrated that an increase in the ketamine concentration, starting from 30 µM, gradually decreased the neuronal calcium oscillation amplitude. The inhibition of the calcium oscillation frequency by 300 µM ketamine was statistically significant, and the neuronal calcium oscillations were completely eliminated with the administration of 3,000 µM Ketamine. The administration of 100, 300, and 1,000 µM NMDA to the 1 mM ketamine-pretreated hippocampal neurons restored the frequency and amplitude of the calcium oscillations in a dose-dependent manner. In fact, a concentration of 1,000 µM NMDA completely reversed the decrease in the calcium oscillation frequency and amplitude that was induced by 1 mM ketamine. This study revealed that ketamine can inhibit the frequency and amplitude of the calcium oscillations in developing hippocampal neurons though the NMDAR (NMDA receptor) in a dose-dependent manner, which might highlight a possible underlying mechanism of ketamine toxicity on the rat hippocampal neurons during development.