This study aimed to understand the impact of sex on the neurocognitive function of patients with Parkinson’s disease (PD). Ninety-four participants with idiopathic PD and 167 age-matched healthy individuals as normal controls (NCs) were recruited and underwent comprehensive neuropsychological assessments. Sex differences were found in NCs, but not in patients with PD. Among male participants, patients with PD showed worse performance on the Digit Symbol Substitution (DSS) (p < 0.001) test and Symbol Search (SS) (p < 0.001) than NCs. Among female participants, patients with PD showed worse performance on the category score of the Modified Wisconsin Card Sorting Test (p < 0.001), SS (p < 0.001), and pentagon copying (p < 0.001) than NCs. After controlling for the effects of age and years of education, Hoehn and Yahr stage was found to predict the performance of the Color Trails Test part A (βA = 0.241, pA = 0.036), Stroop Color and Word Test (β = −0.245, p = 0.036), and DSS (β = −0.258, p = 0.035) in men with PD. These results indicate the differential effect of sex on the neurocognitive function among healthy aging and PD populations. The disappearance of sex differences, which is present in healthy aging, in patients with PD suggests a gradual loss of the neuroprotective effect of estrogen after the initiation of the neurodegenerative process. This study also found mental flexibility and visuospatial function to be the susceptible cognitive domains in women with PD, while the disease severity could predict the working memory and processing speed in men with PD.

Effects of puerarin, an active principle contained in the roots of Pueraria lobata (Leguminosae), on the regulation of glucose metabolism in an insulin deficient state were investigated in cultured myoblast C₂C₁₂ cells using glucose uptake as indicator. Puerarin enhanced the uptake of radioactive glucose into C₂C₁₂ cells in a concentration-dependent manner, which was abolished by prazosin pretreatment. Activation of α₁-adrenoceptors by puerarin was further indicated by the displacement of [³ H]prazosin binding in C₂C₁₂ cells. The stimulatory action of puerarin on glucose uptake was also reduced in C₂C₁₂ cells pre-incubated with the antagonists, both WB 4101 and RS 17 056, at concentrations sufficient to block α_1A-adrenoceptor (α_1A-AR). An activation of α_1A-AR seems responsible for the action of puerarin in C₂C₁₂ cells. Pharmacological inhibition of phospholipase C (PLC) by U73312 resulted a concentration-dependent decrease of puerarin-stimulated glucose uptake in C₂C₁₂ cells. This inhibition of glucose uptake by U73122 was specific because the inactive congener, U73343, failed to block puerarin-stimulated glucose uptake. Moreover, both chelerythrine and GF 109203X diminished the action of puerarin at concentration sufficient to inhibit protein kinase C (PKC). The obtained data suggest that an activation of α_1A-AR by puerarin in C₂C₁₂ cells may increase the glucose uptake via the PLC-PKC pathway.

Danshen has been widely used for the treatment of central nervous system diseases. We investigated the effect of dihydroisotanshinone I (DT), a compound extracted from Danshen, as well as the corresponding mechanisms in an in vitro-based 6-OHDA-induced Parkinson’s disease (PD) model. SH-SY5Y human neuroblastoma cell lines were pretreated with 6-hydroxydopamine (6-OHDA) and challenged with DT. Subsequently, the cell viability and levels of reactive oxygen species (ROS) and caspase-3 were analyzed. The effect of DT on the 6-OHDA-treated SH-SY5Y cells and the expression of the core circadian clock genes were measured using a real-time quantitative polymerase chain reaction. Our results indicated that DT attenuated the 6-OHDA-induced cell death in the SH-SY5Y cells and suppressed ROS and caspase-3. Moreover, DT reversed both the RNA and protein levels of BMAL1 and SIRT1 in the 6-OHDA-treated SH-SY5Y cells. Additionally, the SIRT1 inhibitor attenuated the effect of DT on BMAL1 and reduced the cell viability. The DT and SIRT1 activators activated SIRT1 and BMAL1, and then reduced the death of the SH-SY5Y cells damaged by 6-OHDA. SIRT1 silencing was enhanced by DT and resulted in a BMAL1 downregulation and a reduction in cell viability. In conclusion, our investigation suggested that DT reduces cell apoptosis, including an antioxidative effect due to a reduction in ROS, and regulates the circadian genes by enhancing SIRT1 and suppressing BMAL1. DT may possess novel therapeutic potential for PD in the future, but further in vivo studies are still needed.

Objective: Stearoyl‐coenzyme A desaturase 1 (SCD1) is a key enzyme in fatty acid metabolism and has been implicated in cancer progression, including head and neck squamous cell carcinoma (HNSCC). The phosphoinositide 3‐kinase (PI3K)‐AKT‐mammalian target of rapamycin (mTOR) signaling pathway is a critical regulator of cellular metabolism and survival in cancer. This study investigates the crosstalk between SCD1 inhibition and the PI3K‐AKT‐mTOR pathway, highlighting the therapeutic potential of targeting SCD1 in HNSCC.Study Design: Basic science.Setting: Laboratory.Methods: Four HNSCC cell lines were utilized to evaluate the relationship between SCD1 and the mTOR signaling pathway. Cell viability was assessed following treatment with various mTOR inhibitors. The effect of AKT‐mTOR signaling on SCD1 expression was examined through pharmacological inhibition and gene silencing approaches. Additionally, the impact of SCD1 knockdown on cell proliferation and survival was analyzed.Results: mTOR inhibitors significantly reduced HNSCC cell viability and downregulated SCD1 expression in a dose‐dependent manner. Inhibition of AKT, a key upstream effector of mTOR, also suppressed SCD1 expression, suggesting that SCD1 is regulated through the PI3K‐AKT‐mTOR axis. Silencing SCD1 independently impaired cancer cell growth and enhanced the cytotoxic effects of mTOR inhibitors, indicating a synergistic anticancer effect.Conclusion: SCD1 is a downstream target of the PI3K‐AKT‐mTOR pathway and contributes to HNSCC cell survival. Dual targeting of SCD1 and the mTOR signaling pathway represents a promising therapeutic strategy for HNSCC treatment. Further investigation is warranted to explore the clinical potential of SCD1 inhibitors in combination with mTOR‐targeted therapies.

(1) Background: The study investigated whether the ankle–brachial index (ABI) and pulse wave velocity (baPWV) could reflect the severity of small vessel disease (SVD) and large artery atherosclerosis (LAA). (2) Methods: A total of 956 consecutive patients diagnosed with ischemic stroke were prospectively enrolled from July 2016 to December 2017. SVD severity and LAA stenosis grades were evaluated via magnetic resonance imaging and carotid duplex ultrasonography. Correlation coefficients were calculated between the ABI/baPWV and measurement values. Multinomial logistic regression analysis was performed to determine predictive potential. (3) Results: Among the 820 patients included in the final analysis, the stenosis grade of extracranial and intracranial vessels was inversely correlated with the ABI (p < 0.001, respectively) and positively correlated with the baPWV (p < 0.001 and p = 0.004, respectively). Abnormal ABI, not baPWV, independently predicted the presence of moderate (adjusted odds ratio, aOR: 2.18, 95% CI: 1.31–3.63) to severe (aOR: 5.59, 95% CI: 2.21–14.13) extracranial vessel stenosis and intracranial vessel stenosis (aOR: 1.89, 95% CI: 1.15–3.11). Neither the ABI nor baPWV was independently associated with SVD severity. (4) Conclusions: ABI is better than baPWV in screening for and identifying the existence of cerebral large vessel disease, but neither test is a good predictor of cerebral SVD severity.