The promoting effect of modified Dioscorea pills on vascular remodeling in chronic cerebral hypoperfusion via the Ang/Tie signaling pathway.

Objective: The objective of this study was to investigate the effect of modified Dioscorea pills (MDP) on microcirculatory remodeling in the hippocampus of rats with chronic cerebral hypoperfusion (CCH) through the angiopoietin (Ang)/tyrosine kinase receptor tyrosine kinase with immunoglobulin-like and EGF-like domains (Ang receptor) 2 (Tie-2) signaling pathways, which may underlie the cognitive improvement observed in CCH rats. Methods: Forty male Sprague-Dawley rats raised under specific pathogen-free conditions were randomly divided into three groups: control group (10 rats), model group (15 rats), and MDP group (15 rats). The rats in the model group and MDP group underwent bilateral common carotid artery occlusion using the 2-vessel occlusion (2-VO) method to induce CCH. Rats in the control group underwent the same surgical procedures as those in the model group, except for ligation and occlusion of the carotid arteries. After 1 week of 2-VO, rats in the MDP group were administered MDP condensed decoction intragastrically at a dose of 1 ml/100 g body weight (prepared by the Preparation Room of Hubei Provincial Hospital of Traditional Chinese Medicine) for 45 days, while rats in the other two groups received normal saline intragastrically with the same dose and duration as the MDP group. After the intervention, all rats were euthanized, and brain perfusion was performed to obtain the hippocampal tissue for analysis. Immunohistochemical staining for CD43 was performed to assess microvessel density (MVD); western blot and the reverse transcription-polymerase chain reaction (RT-PCR) were used to analyze the expression of proteins and genes in angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), Tie-2, and vascular endothelial growth factor (VEGF) proteins and genes in the hippocampal tissue and compute the Ang-1/Ang-2 ratio. Results: MDP treatment reduced neuronal loss and promoted restoration of the damaged hippocampal structure in CCH rats. The model group showed significantly higher MVD (14.93 ± 1.92) compared to the control group (5.78 ± 1.65) (P < 0.01), whereas MDP treatment further increased MVD (21.19 ± 2.62). Western blot and RT-PCR analysis revealed that CCH significantly increased the expression of Ang-1, Ang-2, Tie-2, and VEGF proteins and genes, while MDP treatment further significantly upregulated the expression of these proteins and genes. In addition, MDP significantly elevated the gene and protein expression of the Ang-1/Ang-2 ratio compared to the control group (P = 0.041, P = 0.029). Conclusion: CCH induces microvascular neogenesis in the hippocampus, and MDP promotes angiogenesis and microcirculation remodeling in CCH rats via the Ang/Tie signaling pathway, which may be an important mechanism for its restorative effects on hippocampal perfusion and improvement of cognitive function in CCH rats.

Manipulating the monomer-dimer transformation of a heptamethine cyanine ligand: near infrared chromogenic recognition of biothiols.

A novel absorbance recovery method has been developed for the determination of biothiols with a near-infrared reagent. This method employs a two-reagent system composed of cation heptamethine cyanine (CyL) and Hg2+. The absorbance of CyL, with a maximum peak at 760 nm, was decreased due to addition of Hg2+, but recovered when biothiols were added. Under optimal conditions, the reciprocal extent of recovered absorbance was proportional to the concentration of biothiols. The calibration curves are linear over the range of (0.3-7.0) × 10-6 M for cysteine, (1.0-10.0) × 10-6 M for homocysteine and (1.0-9.0) × 10-6 M for glutathione. Because of the specific affinity of Hg2+for biothiols, there is minimal interference from other amino acids. This method has been successfully applied to the determination of homocysteine in human urine samples with satisfactory results.

Copper and Photocatalytic Radical Relay Enabling Fluoroalkylphosphorothiolation of Alkenes: Modular Synthesis of Fluorine-Containing S-Alkyl Phosphorothioates and Phosphorodithioates.

A photoredox and copper-catalyzed fluoroalkylphosphorothiolation of activated and unactivated alkenes via a radical relay mechanism is reported. By employing fluoroalkyl halides as radical precursors and P(O)SH or P(S)SH compounds as coupling partners, a wide range of ß-monofluoroalkyl-, -difluoroalkyl-, -trifluoromethyl-, or -perfluoroalkyl-substituted S-alkyl phosphorothioates and phosphorodithioates can be easily constructed under mild conditions with good functional group tolerance. Furthermore, this modular reaction system can be successfully applied to late-stage functionalization of bioactive molecules.

Copper-Catalyzed Multicomponent Trifluoromethylphosphorothiolation of Alkenes: Access to CF3-Containing Alkyl Phosphorothioates.

An unprecedented copper-catalyzed multicomponent radical-based reaction involving alkenes, P(O)H compounds, sulfur powder, and Togni reagent II at room temperature has been developed. A variety of highly functionalized CF3-containing S-alkyl phosphorothioates can be directly prepared from a wide range of activated and unactivated alkenes. Moreover, this protocol highlights its potential in the late-stage functionalization of complex molecules and opens up a new avenue for the construction of C(sp3)-S-P bonds.