3-Methyladenine ameliorates surgery-induced anxiety-like behaviors in aged mice by inhibiting autophagy-induced excessive oxidative stress.

BACKGROUND: Postoperative anxiety is a common surgical complication in older patients. Research has recently linked excessive autophagy to several neurological disorders, including anxiety. This study aimed to determine whether 3-Methyladenine (3-MA) administration reduced anxiety-like behaviors in a mouse model following abdominal exploratory laparotomy. METHODS: An abdominal exploratory laparotomy model of postoperative anxiety was established using male C57BL/6 mice aged 20 months. 3-MA (6, 30, and 150 mg/ml) was administered via intracerebroventricular immediately following surgery. The mice were assessed 14 days after surgery using the marble burying, elevated plus maze tests, and local field potential recording in the amygdala. The levels of expression of phosphorylated-Akt, Beclin-1, LC3B, nuclear factor erythroid 2-related factor 2 (Nrf2)-occupied regions in NeuN-positive cells, superoxide dismutase (SOD) activity, malondialdehyde (MDA), and glutathione (GSH) were measured at 24 h after surgery. RESULTS: The injection of 3-MA reversed the increased number of marbles buried, decreased time spent in the open arm, and enhanced θ oscillation power after 14 days of abdominal exploratory laparotomy. In addition, administration of 3-MA reduced the ratio of phosphorylated- to total-Akt, decreased expression in Beclin-1 and LC3B, attenuated MDA levels, and increased the ratio of Nrf2-occupied areas in NeuN-positive cells, SOD activity, and GSH levels under abdominal exploratory laparotomy conditions. CONCLUSIONS: 3-MA improved anxiety-like behaviors in aged mice undergoing abdominal exploratory laparotomy by inhibiting excessive autophagy-induced oxidative stress. These results suggest that 3-MA could be an effective treatment for postoperative anxiety.

[Mechanism of modified Liangge San in treatment of acute respiratory distress syndrome based on network pharmacology and experimental validation].

A network pharmacology-based strategy combined with molecular docking and in vitro validation was employed to investigate potential targets and molecular mechanisms of modified Liangge San(MLGS) against acute respiratory distress syndrome(ARDS). Active ingredients and corresponding targets of MLGS were screened out on the Traditional Chinese Medicines Systems Pharmacology(TCMSP) database, and the disease targets of ARDS were obtained by integrating GeneCards and DisGeNET database. The two were intersected to obtain the potential targets of MLGS against ARDS. Cytoscape 3.7.2 was used to construct a "Chinese medicine-active ingredient-target network" of MLGS and a "regulatory network of MLGS against ARDS". The protein-protein interaction(PPI) network was created on the STRING database platform, and the Metascape database was used to carry out Gene Ontology(GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Subsequently, molecular docking and in vitro experiments were performed to further verify the above findings. A total of 211 active ingredients of MLGS and 54 key targets were obtained. The GO enrichment analysis obtained 709 GO entries(P<0.05), including 457 biological processes(BP), 50 cell components(CC), and 98 molecular functions(MF), mainly involved in lipopolysaccharides, response to reactive oxygen species, and apoptosis signal pathways. KEGG pathway enrichment analysis obtained 266 pathways, mainly involved in the cancer signaling pathways, advanced glycation end-products and their receptors(AGE-RAGE) signaling pathways, fluid shear stress, atherosclerosis, proteoglycan pathway in cancer, nuclear and factor kappa B(NF-κB) signaling pathway. Molecular docking showed that the main active ingredients bound steadily with the targets. The experiments proved that MLGS inhibited the generation of reactive oxygen species and the activation of NF-κB signaling pathway, thereby reducing apoptosis. The study shows that MLGS, through its multiple active ingredients including wogonin and luteolin, can treat ARDS by intervening in various signaling pathways such as NF-κB, inhibiting the inflammatory response and oxidative stress, and reducing apoptosis.

The effect of dexmedetomidine in coracoid approach brachial plexus block under dual stimulation.

BACKGROUND: Coracoid approach brachial plexus block (CABPB) is safe and effective for clinical anesthesia and analgesia. Dual stimulation can enhance the block effect of CABPB when using nerve stimulator. Dexmedetomidine is a highly selective α-adrenoceptor agonist and it can prolong the duration of anesthesia when it is added into local anesthetics. The aim of this study was to assess the effects of dexmedetomidine on the duration of anesthesia and the effective postoperative analgesia time when it was mixed with ropivacaine for CABPB under dual stimulation. METHODS: A total of 60 patients were randomly assigned into 2 groups (groups D and C), 30 patients in each group. CABPB were guided by nerve stimulator under dual stimulation. Each patient received 40 mL of 0.375% ropivacaine (group C), or 40 mL of 0.375% ropivacaine mixed with 1 µg/kg dexmedetomidine (group D). The duration of anesthesia, the effective postoperative analgesia time, sensory and motor block onset time, visual analog scale (VAS), and the cumulative dose of rescue tramadol were recorded. RESULTS: Twenty-eight patients in each group were analyzed. The duration of anesthesia was longer in group D as compared with group C (759 vs 634 minutes, P < .05) and the effective postoperative analgesia time was longer in group D as compared with group C (986 vs 789 minutes, P < .05) too. The onset time of sensory and motor blocks were not significantly different between the 2 groups (P > .05). The VAS was similar in the 2 groups at 6 and 12 hours after block (P > .05), but it was lower in group D at 24 hours after block as compared to group C (P < .05). The cumulative dose of rescue tramadol during the first 48 hours postoperative period was significantly lower in group D as compared to group C (P < .05). No significant changes were observed in vital signs in either group. CONCLUSION: The addition of 1 µg/kg dexmedetomidine to ropivacaine extends the duration of anesthesia and the effective postoperative analgesia time for CABPB under dual stimulation. The VAS at 24 hours after block and the demand for rescue tramadol during the first 48 hours postoperative period are lower as well without side effects in the study group.(Registered in ClinicalTrials.gov id. NCT02961361).

[A Quercetin-Based Fluorescent Probe for the Recognition of Fluorid Ions].

Quercetin (Q) is one of the most common flavonoids present in roots, stems, leaves, flowers and fruits of most plants. In this study, a quercetin-based fluorescent probe for detecting fluorid ions had been proposed. With good selectivity and sensitivity for fluorid ions, Q-based fluorescent probe was easier to prepare, more eco-friendly and more innoxious compared with traditional fluorescent probe obtained by organic chemistry synthesis operation. There was a major fluorescence emission peak at 500 nm for Q in dimethyl sulfoxide (DMSO) when the excitation wavelength was 390 nm. The changes of fluorescence spectra were investigated before and after adding different anions into Q solution. The fluorescence emission intensity of Q even had no change when adding Cl-，Br-，I-，ClO-4，H2PO-4, respectively. While adding fluorid ions, the fluorescence emission intensity of Q was decreased obviously, which suggested fluorid ions could induce fluorescence quenching of Q in DMSO. And the fluorescence emission intensity of Q-F- system had almost no significant change when adding other anions (Cl-，Br-，I-，ClO-4，H2PO-4), which meant the progress for detecting fluorid ions didn't be affected by other anions, and Q showed a good selectivity for fluorid ions. The fluorescence titration spectra showed that the fluorescence emission intensity of Q was decreased with the increase of concentration of fluorid ions, and they were in concentration-dependent manner. The fluorescence titration curve exhibited that the Q as fluorescent probe can be applied to the quantification of fluorid ions with a good linearity (R2=0.991), linear range of 1.0～8.0×10-6 mol·L-1 and the detection limit of 1.0×10-7 mol·L-1. Not only the changes appeared in fluorescence spectra, but also the changes appeared in UV-visible spectra, compared with Q absorption spectrum, the location of band at 375 nm had no change after adding Cl-，Br-，I-，ClO-4，H2PO-4, respectively. However, when adding fluorid ions, the band at 375 nm was shifted to 394 nm, and the color of the solution was changed into dark yellow, which revealed the interactions between Q and fluorid ions. The probable mechanism of fluorid ions inducing fluorescence quenching of Q was obtained with 1H NMR spectrum and the changes of fluorescence emission intensity of Q-F- system in different polar solvents (DMSO containing different concentration of water). The interaction mode about Q and fluorid ions in DMSO was related with hydrogen bond. Both experiments suggested that the possible recognition mechanism on fluorid ions was: fluorid ions were destroyed or weakened by original hydrogen bonds, and were promoted charge transfer within quercetin molecule, which resulted in fluorescence intensity decreasing of quercetin. This method was successfully applied in detecting fluorid ions of samples in DMSO with good recovery.

[Research on THz and Raman Spectra of RNA Nucleobases].

The Infrared and Raman spectra of RNA nucleobases in terahertz (THz) band (1~10 THz) were detected with Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy. The position of all the characteristic peaks and corresponding vibration modes of RNA nucleobase crystals were obtained with Guassian09 software and energy-based fragmentation approach under periodic boundary conditions (PBC-GEBF) method. The computational results were verified to be in accordance with experimental data, which indicated that the powder of RNA nucleobases is amorphous crystal structure. The infrared spectra demonstrated that adenine, guanine and cytosine all have 6 infrared active vibrational modes, while uracil only has 3. Comparing to experimental results, the position and intensity of the absorption peaks were nicely corroborated by the predicted spectrum, except that one weak vibrational frequency at 6.35 THz is missing and two peaks (4.83 and 5.39 THz) merge in the predicted spectrum of guanine; two peaks in 4.3 and 4.79 THz merge into a single one in the calculated spectrum of cytosine; the peaks of thymine in 3.32 and 3.82 THz merged. The computational results of Raman spectra were also verified to be in line with the experimental data. The position and intensity of the characteristics peaks were exactly simulated except that two peaks of guanine in 3.52 and 4.48 THz merged; two peaks in 7.26 and 8.03 THz merge and five peaks (3.57, 4.02, 4.49, 4.89, 5.98 THz) merge in the calculated spectrum of guanine. Through the analysis and identification of the characteristic peaks, it is indicated that the vibration modes of DNA nucleobases in 1~10 THz were derived from collective vibration of molecules in the lattice. The intermolecular hydrogen bond and the weak interaction force contribute greatly to the vibration modes. In addition, as the frequency increases to over 5.5 THz, the vibration modes will change from the atoms collective vibration to some atoms vibration. This research has important theoretical and practical reference value to reveal the effect of RNA nucleobases in the areas of RNA molecular structure constitution, biological macromolecules identification and terahertz spectra formation mechanism and biological inheritance.