Linking oxidative DNA lesion 8-OxoG to tumor development and progression.

Cells of the aerobic metabolic organism are inevitably subjected to the damage from reactive oxygen species (ROS). ROS cause multiple forms of DNA damage, among which the oxidation product of guanine G 8-hydroxyguanine (8-oxoG) is the most frequent DNA oxidative damage, recognized by the specific glycosidase OGG1 that initiates the base excision repair pathway. If left unrepaired, 8-oxoG may pair with A instead of C, leading to a mutation of G: C to T: A during replication. Thus, the accumulation of 8-oxoG or the abnormal OGG1 repair is thought to affect gene function, which in turn leads to the development of tumor or aging-related diseases. However, a series of recent studies have shown that 8-oxoG tends to be produced in regulatory regions of the genome. 8-oxoG can be regarded as an epigenetic modification, while OGG1 is a specific reader of this information. Substrate recognition, binding or resection by OGG1 can cause DNA conformation changes or affect histone modifications, causing up-regulation or down-regulation of genes with different properties. Thus, in addition to the potential genotoxicity, the association of guanine oxidative damage with development of tumors is closely related to its aberrant initiation of gene expression through epigenetic mechanisms. In this review, we summarize the underlying mechanism of 8-oxoG and repair enzyme OGG1 in tumor development and progression, with aims to interpret the relationship between DNA oxidative damage and tumor from a new perspective, and provide new ideas and targets for tumor treatment.

Stereoselective Iron-Catalyzed Alkylation of Enamides with Cyclopropanols via Oxidative C(sp2)-H Functionalization.

Established herein is a radical-mediated C-H alkylation of enamides with cyclopropanols. An environmentally benign catalytic system with iron salt and air is used to permit the oxidative coupling process. The protocol demonstrates a broad substrate scope, allowing the stereoselective synthesis of alkylated enamides. The value of this strategy is further reflected by late-stage diversification of complex cyclopropanol-containing molecules and downstream transformations. Mechanistic studies reveal the dual role of iron salt in the reaction.

[Study on brain tissue characteristics of rat model of Parkinson's disease based on functionality near-infrared spectroscopy (fNIRs) technology].

Functionality near infrared spectroscopy (fNIRs) technology was utilized in the present paper to explore functional properties of brain tissue of rat model of Parkinson's disease(PD). Imaging data of rat model were detected by small animal MRI and CT; and characteristic parameters of striatum of rat brain were detected by fNIRs system. Experimental results show that, between PD and normal rat, there is no obvious change in morphological structure, but significant differences existed in reduced scattering coefficient (mu's) and cerebral blood volume (CBV) of rat striatum; there exists correlation between parameters (mu's, CB3V) obtained by fNIRs and parameters (cerebral blood flow (CBF), CBV) obtained by CT perfusion (CTP). These results indicate that fNIRs can be used as important reference for PD research.

[Study on assessment of effects of mannitol on treatment of TBE based on measurement of mini-invasive optical parameter (micro'(s))].

Near infrared spectroscopy (NIRs) technology was utilized for assessing effects in treating traumatic brain edema (TBE). Firstly, models for rats with traumatic brain edema were copied according to Feeney's apparatus. Then rats were given mannitol with different dosages (large and little) according to their groups. Simultaneously rat's brain tissues were monitored in vivo and real-time by NIRs mini-invasive detector developed by the authors' laboratory. And the water content of the brain tissues was measured by the wet and dry weight method at 1, 6, 24, 72 and 120 h after the injury and the treatment. Then, effects in treating TBE with different dosages were assessed by analyzing reduced scattering coefficient (micro'(s)) data measured by NIRs and brain water content (BWC) before and after injecting dehydration. Finally, the authors found that reduced scattering coefficient (micro'(s)) of rat's local cortex is a good indicator of assessing effects of treatment of TBE and that may be a preferable approach to assessing effects in vivo and real-time in treatment of brain injury.

[Research on traumatic brain real-time monitoring by near-infrared technology].

In order to monitoring the development of traumatic brain edema in vivo, a specifically designed optical parameters of tissue testing system with a mini-invasion bifurcated optical fiber probe and a fiber spectrometer was used to monitor the reduced scattering coefficient (mu's) of t he rat traumatic brain while the counterpart parameter, i. e. brain water content (BWC), was also measured. Acute rat regional brain trauma was applied according to Feeney's apparatus. The changes of brain edema were monitored by near-infrared spectroscopy (NIRS) technology and by measuring the water content of the brain. Experiment result showed that distinct brain edema in injured areas was found at 6 hours later after trauma, which reached a summit of severity at 24-72 hours later after trauma, then gradually declined. After using the dehydrant, the brain edema situation became better, and then, the edema occurred again whilet he medicamentosus effect of dehydrant was gradually lost. It can be showed that mu's had similar change profile with BWC and the two parameters were well linearly relative to each other. mu's is a good indicator for monitoring traumatic brain edema and t he medicamentosus effect of dehydrant. As a result near-infrared spectroscopy is a new feasible method of monitoring the development of traumatic brain edema in vivo.

Detection of unexpected frauds: Screening and quantification of maleic acid in cassava starch by Fourier transform near-infrared spectroscopy.

Fourier transform near-infrared (FT-NIR) spectroscopy and chemometrics were adopted for the rapid analysis of a toxic additive, maleic acid (MA), which has emerged as a new extraneous adulterant in cassava starch (CS). After developing an untargeted screening method for MA detection in CS using one-class partial least squares (OCPLS), multivariate calibration models were subsequently developed using least squares support vector machine (LS-SVM) to quantitatively analyze MA. As a result, the OCPLS model using the second-order derivative (D2) spectra detected 0.6%(w/w) adulterated MA in CS, with a sensitivity of 0.954 and specificity of 0.956. The root mean squared error of prediction (RMSEP) was 0.192(w/w, %) by using the standard normal variate (SNV) transformation LS-SVM. In conclusion, the potential of FT-NIR spectroscopy and chemometrics was demonstrated for application in rapid screening and quantitative analysis of MA in CS, which also implies that they have other promising applications for untargeted analysis.

Pharmacokinetic Analysis of Four Bioactive Iridoid and Secoiridoid Glycoside Components of Radix Gentianae Macrophyllae and Their Synergistic Excretion by HPLC-DAD Combined with Second-Order Calibration.

An HPLC-DAD method combined with second-order calibration based on the alternating trilinear decomposition (ATLD) algorithm with the aid of region selection was developed to simultaneously and quantitatively characterize the synergistic relationships and cumulative excretion of the four bioactive ingredients of Radix Gentianae Macrophyllae in vivo. Although the analytes spectra substantially overlapped with that of the biological matrix, the overlapping profiles between analytes and co-eluting interferences can be successfully separated and accurately quantified by the ATLD method on the basis of the strength of region selection. The proposed approach not only determined the content change but also revealed the synergistic relationships and the cumulative excretion in vivo of the four ingredients in urine and feces samples collected at different excretion time intervals. In addition, several statistical parameters were employed to evaluate the accuracy and precision of the method. Quantitative results were confirmed by HPLC-mass spectrometry. Satisfactory results indicated that the proposed approach can be utilized to investigate the pharmacokinetics of Radix Gentianae Macrophyllae excretion in vivo.

Three-Way Laryngeal Mask Reduces Anesthesia-Related Stress Responses in Bronchoalveolar Lavage: An Experimental Canine Study.

OBJECTIVE: To compare the ventilatory effects of the three-way laryngeal mask airway (TLMA) and tracheal tube (TT) on hemodynamics, respiratory function, and stress responses in a canine model during bronchoalveolar lavage (BAL). STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: The 303rd Hospital of the Chinese People's Liberation Army in May 2013. METHODOLOGY: Sixteen dogs were divided into two groups. MAP, SpO2 and HR were recorded before anesthesia (T0), immediately before intubation (T1), during intubation (T2), at 3 (T3) and 10 (T4) minutes after mechanical ventilation, at 10 (T5), 20 (T6), and 30 (T7) minutes during the course of BAL, during extubation (T8), and 3 minutes after extubation (T9). Tidal volume, peak inspiratory airway pressure, and expiratory CO2 pressure were recorded at time points T2, T5, T6, T7, and T8. Stress responses variables, including epinephrine and norepinephrine levels, were examined at time points T0, T2, T3, T5, T8, and T9. RESULTS: BAL was successfully completed in all animals. In comparison to the TT, the TLMA was capable of maintaining hemodynamic stability and ventilation (p < 0.05), and producing less stress responses (p < 0.05). CONCLUSION: In a canine model, ventilation with the TLMA was better than the TT during BAL in terms of maintaining effective ventilation and stable hemodynamics, and producing less stress responses.

"Turn-off-on" fluorescent sensor for (N-methyl-4-pyridyl) porphyrin -DNA and G-quadruplex interactions based on ZnCdSe quantum dots.

As a new detection model, the reversible fluorescence "turn-off-on" sensor based on quantum dots (QDs) has already been successfully employed in the detections of many biochemical materials, especially in the researches on the interactions between anticancer drugs. The previous studies, however, mainly focused on simple-structured oligonucleotides and Calf thymus DNA. G-quadruplex, an important target for anti-cancer drug with special secondary structure, has been stimulating increasing research interests. In this paper, we report a new detection method based on the fluorescence "turn-off-on" model with water-soluble ZnCdSe QDs as the fluorescent probe, to analyze the interactions between anticancer drug (N-methyl-4-pyridyl) porphyrin (TMPyP) and nucleic acid, especially the G-quadruplex. The fluorescence of QDs can be quenched by TMPyP via photo-induced electron transfer and fluorescence resonance energy transfer, while on the other hand, the combination between TMPyP and G-quadruplex releases QDs from their quenchers and thus recovers the fluorescence. Most importantly, the fluorescence "turn-off-on" model has been employed, for the first time, to analyze the impacts of special factors on the interaction between TMPyP and G-quadruplex. The excellent selectivity of the system has been verified in the studies of the interactions between TMPyP and different DNAs (double-stranded DNA, single-stranded G-quadruplex, and different types of G-quadruplexes) in Na(+) or K(+)-containing buffer.

[Value of magnesium sulfate and/or valium in preventing local anesthetic toxicity of sacral block].

OBJECTIVE: To study the effects of magnesium sulfate and/or valium in preventing local anesthetic toxicity induced by sacral block. METHODS: A total of 240 adult patients scheduled for sacral block were randomized equally into four groups matched for sex, age and body weight. Ten minutes before sacral block, the patients in group B received valium (0.1 mg/kg), group C received magnesium sulfate (50 mg/kg), group D received both valium (0.1 mg/kg) and magnesium sulfate (50 mg/kg). The control (group A) received neither valium nor magnesium sulfate. Local anesthetic toxicity was observed and recorded in all the groups. RESULTS: Local anesthetic toxicity was significantly decreased in group B and group C compared with group A (P<0.05), and the toxicity was even more significantly decreased in group D(P<0.01 vs group A). CONCLUSION: Local anesthetic toxicity of sacral block can be significantly decreased by intravenous injection of valium or magnesium sulfate, and their combination produces stronger effects.

Solution-phase parallel synthesis of 3,5,6-substituted indolin-2-ones.

A practical and efficient new parallel method has been developed for the synthesis of 3-substituted indolin-2-ones with a large variety of substituents at the 5- and 6-positions using 1,5-difluoro-2,4-dinitrobenzene. This 3,5,6-substituted indolin-2-one skeleton possesses three points of diversification and, thus, affords new opportunities for identification and optimization of leads in drug discovery.

Simultaneous solid-phase synthesis of quinoxalinone and benzimidazole scaffold libraries.

This article describes a method for simultaneous solid-phase synthesis of a quinoxalinone and benzimidazole scaffold library that consists of 240 members. The library was generated by using the solid-phase "split-and-pool" approach and the IRORI sorting system.