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Geniposidic 4-isoamyl ester (GENI) with anti-aging effects is a new iridoid glycoside derivative from Gardenia jasminoides Ellis found in our previous study. In this study, to indicate whether this compound has anti-Alzheimer's disease (AD) effect, the galactose-induced AD mice and naturally aging mice with AD were used to do drug efficacy evaluation. Furthermore, the Western blot, small interfering RNA (siRNA), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CESTA), liquid chromatography-tandem mass spectrometry (LC/MS-MS), adenosine 5′-monophosphate-activated protein kinase (AMPK) mutants and surface plasmon resonance (SPR) analysis were utilized to clarify the mechanism of action and identify target protein of this molecule. GENI exerts anti-AD efficacy in galactose-induced AD mice and naturally aging mice with AD through neuroprotection and modification of autophagy and neuron inflammation. Moreover, AMPK as the target protein of GENI to produce an anti-AD effect is identified and the ASP148, ASP157, and ASP166 of the AMPK α subunit and lysine (LYS)148, aspartic acid (ASP)156, LYS309, and ASP316 in the AMPK γ subunit as binding sites are confirmed. Meanwhile, the AMPK/unc-51-like autophagy-activating kinase 1 (ULK1)/microtubule-associated protein 1 light chain 3 beta (LC3B) and AMPK/mammalian target of rapamycin (mTOR) signaling pathways involved in anti-AD effects of GENI. The findings provide a new perspective on treating neurodegenerative diseases by activating AMPK for the energy metabolism disorder. [ABSTRACT FROM AUTHOR]

Background: Both the trauma of endometrium and hysteroscopic adhesiolysis can lead to a high rate of placenta accreta spectrum (PAS) in women with intrauterine adhesion (IUA). This study analysed the impact of time interval from adhesiolysis to pregnancy on PAS in IUA women. Methods: Patients diagnosed with IUA who underwent adhesiolysis in Anhui Women and Children's Medical Centre between January 2016 and December 2020 were included in this case-series study. Clinical data were obtained from electronic medical records and telephone interviews. Results: Among a total of 102 IUA women with successful pregnancies, 8 (7.8%) suffered from miscarriages with PAS, and 94 (92.2%), 47 with PAS and 47 without PAS, had successful delivery. The total prevalence of PAS in pregnant women with IUA was 53.9% (55/102). The average time from adhesiolysis to pregnancy in the PAS group was significantly longer than in the non-PAS group (14.2 ± 5.7 vs. 10.3 ± 4.4 months, p = 0.000). Regression analysis showed that AFS grade (OR = 7.40, 95% CI 1.38–39.73, p = 0.020) and adhesiolysis to pregnancy interval time between 12 and 24 months (OR = 12.09, 95% CI 3.76–38.83, p = 0.000) were closely related to PAS. A Kaplan–Meier analysis showed the median interval time to PAS was 16.00 months (95% CI 15.11–16.89). Conclusions: We assume that prolonged adhesiolysis to pregnancy interval may be considered a significant risk factor for PAS in IUA women. PLAIN LANGUAGE SUMMARY: Both the trauma of endometrium and hysteroscopic adhesiolysis can result in a high rate of placenta accreta spectrum in women with intrauterine adhesion. This study analysed the impact of time interval from adhesiolysis to pregnancy on placenta accreta spectrum in intrauterine adhesion women. This case-series study included patients diagnosed with intrauterine adhesion who underwent adhesiolysis in Anhui Women and Children's Medical Centre between January 2016 and December 2020. Clinical data were obtained from electronic medical records and telephone interviews. We assume that prolonged adhesiolysis to pregnancy interval may be considered a significant risk factor for placenta accreta spectrum in intrauterine adhesion women. [ABSTRACT FROM AUTHOR]