Sleep deprivation: A risk factor for the pathogenesis and progression of Alzheimer's disease.

Sleep deprivation refers to an intentional or unintentional reduction in sleep time, resulting in insufficient sleep. It is often caused by sleep disorders, work demands (e.g., night shifts), and study pressure. Sleep deprivation promotes Aß deposition and tau hyperphosphorylation, which is a risk factor for the pathogenesis and progression of Alzheimer's disease (AD). Recent research has demonstrated the potential involvement of sleep deprivation in both the pathogenesis and progression of AD through glial cell activation, the glial lymphatic system, orexin system, circadian rhythm system, inflammation, and the gut microbiota. Thus, investigating the molecular mechanisms underlying the association between sleep deprivation and AD is crucial, which may contribute to the development of preventive and therapeutic strategies for AD. This review aims to analyze the impact of sleep deprivation on AD, exploring the underlying pathological mechanisms that link sleep deprivation to the initiation and progression of AD, which offers a theoretical foundation for the development of drugs aimed at preventing and treating AD.

Association between stroke and venous leg ulcers: A Mendelian randomization study.

To investigate any potential bidirectional causal relationships between stroke and venous leg ulcers (VLUs), Mendelian randomization (MR) analyses were carried out in this study. The exposure factor was stroke, the outcome factor was VLUs. The two-sample MR study was carried out based on the online analysis platform (http://app.mrbase.org/). The association of stroke and VLUs was analysed via methods of Inverse Variance Weighted (IVW), Weighted Median, MR-Egger and weighted mode. IVW method suggested no association between stroke and VLUs ((ß 1.06; SE 9.321; p = 0.9095)). Weighted median estimator (ß 5.906; SE 11.99, p = 0.6223), MR-Egger (ß -0.8677; SE 21.89; p = 0.9691) and weighted mode (ß 9.336; SE 17.77; p = 0.6089) showed consistent results. Conversely, evidence indicating that the presence of VLUs increased the risk of stroke was lacking. According to this MR study, there is no causal connection between stroke and VLUs, which suggests that therapies targeting stroke may not be effective against VLUs.

Combination treatment of Danggui Buxue Decoction and endothelial progenitor cells can enhance angiogenesis in rats with focal cerebral ischemia and hyperlipidemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Buxue Decoction (DBD) is a classic prescription of traditional Chinese medicine that is mainly used for treating clinical anemia for more than 800 years. This prescription has been utilized for nourishing "Qi" and enriching "Blood" for women suffering from menopausal symptoms. Meanwhile, DBD has the role of improving angiogenesis and promoting the neuroprotective functions. Bone marrow-derived endothelial progenitor cells (EPCs) was suboptimal to treat the focal cerebral ischemia (FCI). Thus, it's may be a novel strategy of DBD combined with EPCs transplantation for the FCI. AIM OF THE STUDY: To investigate the mechanistic effects of DBD in combination with EPCs transplantation to improve behavioral function of the FCI and hyperlipidemia. MATERIALS AND METHODS: We used rats with hyperlipidemia to develop a FCI model using photo-thrombosis, and treated the DBD in combination with EPCs transplantation. We adopted the Modified Neurological Severity Score to evaluate the neurological deficit, undertook the 2,3,5-triphenyltetrazolium chloride staining to calculate the total infarct volume. We carried out the RT-qPCR, Immunohistochemical analyses, TUNEL, ELISA, and Western blotting to measure the gene and protein levels which related to anti-apoptosis mechanisms and angiogenesis. RESULTS: Administration of DBD in combination with EPCs transplantation was found to improve behavioral function, reducing the infarct volume and decrease the level of total-cholesterole (TC) and low-density lipoprotein-cholesterol (LDL-C). Treatment of DBD plus EPCs increased the mRNA and protein expression of vascular endothelial growth factor A, fibroblastic growth factor-2, and angiopoietin-1 and decreased the apoptosis of endothelial cells by activating the phosphoinositide 3-kinase/protein kinase B/Bcl-xL/Bcl-2 associated death promoter (PI3K/Akt/BAD) pathway and promoting activation of the extracellular signal-regulated kinase (ERK) pathway, which induced angiogenesis directly. CONCLUSIONS: Our findings provided that DBD administration combined with EPCs transplantation promoted reconstruction of nervous function. This was achieved by enhancing expression of the growth factors related to anti-apoptosis mechanisms and angiogenesis thanks to regulation of the PI3K/Akt/BAD and ERK signaling pathways, and might be relate to the lowering of TC and LDL-C levels.