Intravoxel incoherent motion magnetic resonance imaging in the assessment of brain microstructure and perfusion in idiopathic normal-pressure hydrocephalus.

PURPOSE: To determine the relationship between intravoxel incoherent motion (IVIM) MRI parameters and clinical changes post-tap test (TT) in idiopathic normal-pressure hydrocephalus (iNPH) patients. METHODS: Forty-four probable iNPH patients underwent 3 T MRI before and after TT. IVIM parameters were calculated from eight different bilateral regions of interest in basal ganglia, centrum semiovale, and corona radiata. Patients were categorized based on TT response into positive (group 1) and negative (group 2) groups. A Welch two-sample t-test was used to compare differences in D, D*, f, and ADC between the two groups, while a paired t-test was employed to assess the changes within each group before and after TT. These parameters were then correlated with clinical results. RESULTS: In the lenticular and thalamic nuclei, D value was significantly lower in the group 1 compared to group 2 both pre- and post-TT (p = 0.002 and p = 0.007 respectively). Post-TT, the positive response group exhibited a notably reduced D* value (p = 0.012) and significantly higher f values (p = 0.028). In the corona radiata and centrum semiovale, a significant post-TT reduction in D* was observed in the positive response group (p = 0.017). Within groups, the positive response cohort showed a significant post-TT increase in ADC (p < 0.001) and a decrease in D* (p = 0.007). CONCLUSION: IVIM permits the acquisition of important non-invasive information about tissue and vascularization in iNPH patients. Enhanced perfusion in the lenticular and thalamic nuclei may suggest the role of re-established microvascular and glymphatic pathways, potentially elucidating the functional improvement in motor function after TT in iNPH patients.

3,5-Dicaffeoylquinic Acid Lowers 3T3-L1 Mitotic Clonal Expansion and Adipocyte Differentiation by Enhancing Heme Oxygenase-1 Expression.

Adipogenesis is a complex process in which cell commitment and mitotic clonal expansion (MCE) are in-sequence crucial events leading to terminal adipocyte differentiation. The molecules able to block some key signals in this cascade can hamper adipogenesis becoming promising agents to counteract hyperplasia and hypertrophy of adipose tissue. Mono- and di-caffeoylquinic acid isomers are biologically active polyphenols, displaying in vitro and in vivo antioxidant, hepatoprotective, anti-diabetic and anti-obesity properties. Among these isomers, 3,5-dicaffeoylquinic acid (DCQA) has been reported to inhibit lipid accumulation in adipose cells more successfully than others. Thus, we investigated DCQA effects and molecular mechanisms on 3T3-L1 pre-adipocytes induced to differentiate with a hormonal cocktail (MDI). Oil Red O incorporation assessed that DCQA pre-treatment inhibited lipid accumulation in 3T3-L1 cells induced to differentiate for 10 days. At this time, an increased phosphorylation of both AMP-activated kinase and acetyl-CoA carboxylase, as well as a strong decrease in fatty acid synthase protein level, were registered by immunoblotting, thereby suggesting that DCQA treatment can reduce fatty acid anabolism in 3T3-L1 adipocytes. Furthermore, BrdU incorporation assay, performed 48 h after hormonal stimulation, revealed that DCQA treatment was also able to hinder the 3T3-L1 cell proliferation during the MCE, which is an essential step in the adipogenic process. Thus, we focused our attention on early signals triggered by the differentiation stimuli. In the first hours after hormonal cocktail administration, the activation of ERK1/2 and Akt kinases, or CREB and STAT3 transcription factors, was not affected by DCQA pre-treatment. Whereas 24 h after MDI induction, DCQA pre-treated cells showed increased level of the transcription factor Nrf2, that induced the expression of the antioxidant enzyme heme oxygenase 1 (HO-1). In control samples, the expression level of HO-1 was reduced 24 h after MDI induction in comparison with the higher amount of HO-1 protein found at 2 h. The HO-1 decrease was functional by allowing reactive oxygen species to boost and allowing cell proliferation induction at the beginning of MCE phase. Instead, in DCQA-treated cells the HO-1 expression was maintained at high levels for a further 24 h; in fact, its expression decreased only 48 h after MDI stimulation. The longer period in which HO-1 expression remained high led to a delay of the MCE phase, with a subsequent inhibition of both C/EBP-α expression and adipocyte terminal differentiation. In conclusion, DCQA counteracting an excessive adipose tissue expansion may become an attractive option in obesity treatment.

Activity and stability studies of verbascoside, a novel antioxidant, in dermo-cosmetic and pharmaceutical topical formulations.

We here report the results of our investigations carried out on verbascoside, a phenylpropanoid glycoside known for its antioxidant, anti-inflammatory and photoprotective actions. Verbascoside was obtained from Buddleia davidii meristematic cells, obtained in turn using a sustainable biotechnology platform which employs an in vitro plant cell culture technology. Verbascoside was first investigated to assess the behaviour of the active ingredient in solution or in finished preparations, in view of its potential topical use, especially in skin protection. Stability studies were performed by HPLC, and a PCL assay was adopted to determine the radical scavenging activity toward superoxide anion. The high hydrophilic character of verbascoside, suggested in a somewhat limited range of possible applications, leading us to explore its derivatization to obtain the semi-synthetic derivative VPP, an acyl derivative of verbascoside, with an improved range of applications due to its lower hydrophilic profile. Alone, VPP revealed increased antioxidant activity, both as an active ingredient and in dermocosmetic preparations. Stability studies showed a greater stability of VPP in lipophilic vehicles, whereas the parent verbascoside proved more stable in an O/W emulsions. Verbascoside was also stable in suppositories, an interesting pharmaceutical form for possible applications in treatment of inflammation of the intestinal mucosa.