Shugan Jieyu capsule effects on peripheral blood micro-124, micro-132, and brain-derived neurotrophic factor in patients with mild to moderate depression.

BACKGROUND: To assess the effectiveness of Shugan Jieyu capsules on peripheral blood miR-124, miR-132, and brain-derived neurotrophic factor (BDNF) levels in patients with mild to moderate depression following coronary artery intervention [percutaneous coronary intervention (PCI)] for coronary heart disease. AIM: To evaluate the therapeutic efficacy of Shugan Jieyu capsules and their effects on the peripheral blood levels of miR-124, miR-132, and BDNF in patients with mild to moderate depression following PCI for coronary heart disease. METHODS: Patients with mild-to-moderate depression of the liver-qi stagnation type after PCI for coronary heart disease at the 305th Hospital of the People's Liberation Army were enrolled from June 2022 to November 2023 and randomly assigned to two groups: Experimental (treated with Shugan Jieyu capsules) and control (treated with escitalopram oxalate tablets). This study compared the antidepressant effects of these treatments using 17-item Hamilton Rating Scale for Depression (HAMD-17) scores, metabolic equivalents, low-density lipoprotein cholesterol, BDNF, high-sensitivity C-reactive protein levels, miR-124 and miR-132 levels, distribution of immune-related lymphocyte subsets, and traditional Chinese medicine syndrome scores before and after 6 weeks of treatment. RESULTS: No significant difference was observed in any index between the two groups before treatment (P > 0.05). After treatment, the total efficacy rates were 93.33% and 90.00% in the experimental and control groups, respectively. Experimental group had significantly lower scores for the main and secondary syndromes compared to the control group (P < 0.05). No significant difference was observed in the metabolic equivalents between the two groups before and after treatment (P > 0.05). The levels of low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and miR-132 were significantly lower, whereas those of miR-124, BDNF, CD3+T lymphocytes, CD3+CD4+T helper lymphocytes, and CD3+CD4+/CD3+CD8+ cells were significantly higher in the experimental group compared to the control group (P < 0.05). The incidence of adverse reactions during experimental group was significantly lower than that in control group (P < 0.05). CONCLUSION: Shugan Jieyu capsules have good efficacy in patients with mild-to-moderate depression after PCI, and its mechanism may contribute to the regulation of miR-124, miR-132, BDNF levels, and lymphoid immune cells.

Reaction profiling by ultra high-pressure liquid chromatography/time-of-flight mass spectrometry in support of the synthesis of DNA-encoded libraries.

An ultra high-pressure liquid chromatography/mass spectrometry (UHPLC/MS) separation and analysis method has been devised for open access analysis of synthetic reactions used in the production of DNA-encoded chemical libraries. The aqueous mobile phase is 100mM hexafluoroisopropanol and 8.6mM triethylamine; the organic mobile phase is methanol. The UHPLC separation uses a C18 OST column (50mm×2.1mm×1.7µm) at 60°C, with a flow rate of 0.6mL/min. Gradient concentration is from 10 to 40% B in 1.0min, increasing to 95% B at 1.2min. Cycle time was about 5min. This method provides a detection limit of a 20-mer oligonucleotide by mass spectrometry of better than 1pmol on-column. Linear UV response for 20-mer extends from 2 to 200pmol/µL in concentration, same-day relative average deviations are less than 5% and bias (observed minus expected) is less than 10%. Deconvoluted mass spectra are generated for components in the predicted mass range using a maximum entropy algorithm. Mass accuracy of deconvoluted spectra is typically 20ppm or better for isotopomers of oligonucleotides up to 7000Da.

Synthesis of novel bicyclo[4.1.0]heptane and bicyclo[3.1.0]hexane derivatives as melanin-concentrating hormone receptor R1 antagonists.

To address the hERG liability of MCHR1 antagonists such as 1 and 2, new analogs such as 4 and 5 that incorporated a polar heteroaryl group were designed and synthesized. Biological evaluation confirmed that these new analogs retained MCH R1 activity with greatly attenuated hERG liabilities as indicated in the Rb efflux assay.

Design, synthesis, and evaluation of tetrahydroquinoline and pyrrolidine sulfonamide carbamates as gamma-secretase inhibitors.

Gamma-secretase is a key enzyme involved in the production of beta-amyloid peptides which are believed to play a critical role in the onset and progression of Alzheimer's disease (AD). As such, inhibition of gamma-secretase has been an attractive approach to AD therapy. In this paper, the design, synthesis, and evaluation of tetrahydroquinoline and pyrrolidine sulfonamide carbamates as gamma-secretase inhibitors are described.

Discovery of tetralin ureas as potent melanin concentrating hormone 1 receptor antagonists.

Melanin concentrating hormone (MCH) plays an important role in the regulation of food intake and energy balance in mammals. MCH-1 receptor (MCH1R) deficient mice are lean and resistant to diet-induced obesity. As such, MCH1R antagonists are believed to have potential as possible treatments for obesity. The discovery of a novel class of tetralin ureas as potent MCH1R antagonists is described herein.

Discovery and SAR of biaryl piperidine MCH1 receptor antagonists through solid-phase encoded combinatorial synthesis.

An encoded combinatorial library based on aryl and biaryl piperidine scaffolds was designed and synthesized. Screening of this library resulted in the discovery of high-nanomolar biaryl piperidine-based MCH1 receptor antagonists. Follow-up optimization using a parallel synthesis provided potent, single digit nanomolar antagonists.

Discovery and SAR of 4-amino-2-biarylbutylurea MCH 1 receptor antagonists through solid-phase parallel synthesis.

-4-Amino-2-arylbutylbenzamides such as 1 were identified as micromolar MCH 1 receptor (MCH1R) antagonists via screening using a scintillation proximity assay based on [125I]-MCH binding to recombinant, human MCH1R. Subsequent lead optimization efforts using solid-phase parallel synthesis resulted in the defined structure-activity relationships and the identification of 4-amino-2-biarylbutylureas, such as 11g, as potent single digit nanomolar MCH1R antagonists.