ABSTRACTMost breast cancer survivors receiving chemotherapy have severe cognitive impairment, often referred to as “chemobrain.” Polydatin (PLD) is known to have many biological activities. Thus, this study aimed to determine whether symptoms of chemobrain can be prevented or relieved by PLD. The chemobrain models were established by intraperitoneal injection of doxorubicin (DOX, 2 mg/kg) in rats once a week for 4 weeks (DOX group and DOX+PLD group). In the PLD group and DOX+PLD group, PLD (50 mg/kg) was administered orally to rats every day. We found that PLD treatment significantly protected against DOX-induced learning and memory impairment, restored hippocampal histopathological architecture. Furthermore, PLD suppressed DOX-induced oxidative stress through up-regulating Nrf2, inhibited inflammatory response by activating the NF-κB pathway, and reduced hippocampal apoptosis. Therefore, the present study indicated that PLD offered neuroprotection against DOX-induced chemobrain. PLD may assist in preventing chemobrain after chemotherapy in patients with cancers. 相似文献
Cerebral ischaemia/reperfusion (I/R) injury-induced irreversible brain injury is a major cause of mortality and functional impairment in ageing people. Gastrodin (GAS), derived from the traditional Chinese herbal medicine Tianma, has been reported to inhibit the progression of stroke, but the mechanism whereby GAS modulates the progression of cerebral I/R remains unclear. The middle cerebral artery occlusion method was used as a model of I/R in vivo. Rats were pretreated with GAS by intraperitoneal injection 7 days before I/R surgery and were then treated with GAS for 7 days after I/R surgery. Additionally, an oxygen–glucose deprivation/reoxygenation model using neuronal cells was established in vitro to simulate I/R injury. 2,3,5-Triphenyltetrazolium chloride and Nissl staining were used to evaluate infarct size and neuronal damage, respectively. Lactate dehydrogenase release and cell counting kit-8 assays were used to assess neuronal cell viability. Enzyme-linked immunosorbent assay, qPCR, flow cytometry and western blotting were performed to analyse the expression levels of inflammatory factors (IL-1β, IL-18), lncRNA NEAT1, miR-22-3p, NLRP3 and cleaved caspase-1. Luciferase reporter experiments were performed to verify the association between lncRNA NEAT1 and miR-22-3p. The results indicated that GAS could significantly improve the neurological scores of rats and reduce the area of cerebral infarction. Meanwhile, GAS inhibited pyroptosis by downregulating NLRP3, inflammatory factors (IL-1β, IL-18) and cleaved caspase-1. In addition, GAS attenuated I/R-induced inflammation in neuronal cells through the modulation of the lncRNA NEAT1/miR-22-3p axis. GAS significantly attenuated cerebral I/R injury via modulation of the lncRNA NEAT1/miR-22-3p axis. Thus, GAS might serve as a new agent for the treatment of cerebral I/R injury.
Plant extracellular vesicles (EVs) play critical roles in the cross-kingdom trafficking of molecules from hosts to interacting microbes, most notably in plant defense responses. However, the isolation of pure, intact EVs from plants remains challenging. A variety of methods have been utilized to isolate plant EVs from apoplastic washing fluid (AWF). Here, we compare published plant EV isolation methods, and provide our recommended method for the isolation and purification of plant EVs. This method includes a detailed protocol for clean AWF collection from Arabidopsis thaliana leaves, followed by EV isolation via differential centrifugation. To further separate and purify specific subclasses of EVs from heterogeneous vesicle populations, density gradient ultracentrifugation and immunoaffinity capture are then utilized. We found that immunoaffinity capture is the most precise method for specific EV subclass isolation when suitable specific EV biomarkers and their corresponding antibodies are available. Overall, this study provides a guide for the selection and optimization of EV isolation methods for desired downstream applications. 相似文献
As the most important construction features of ancient Chinese cities, the city walls nowadays have lost their function of enemy defense and turned to affect the urban structure and development. To clarify the impact of ancient city walls on modern urban development, this work was conducted to measure the differences of landscape types and levels between the inner and outer walls of three typical ancient Chinese cities with the help of geoinformatics materials and landscape ecology indices. The results of this research proved that city walls have great impact on landscape pattern. Specifically, the aggregation, fragmentation, diversity and evenness of landscape were strongly affected by well-preserved ancient city walls. By sorting out and consulting historical documents and China's “City Walls Protection Regulations”, we also found that city walls help the old city to retain its original style and design characteristics. The findings of this quantitative-analysis-based historical study can provide a theoretical basis for the protection of historical heritage and landscape design.
Alzheimer''s disease (AD) is a leading cause of dementia in elderly individuals and therapeutic options for AD are very limited. Over‐activation of N‐methyl‐D‐aspartate (NMDA) receptors, amyloid β (Aβ) aggregation, a decrease in cerebral blood flow (CBF), and downstream pathological events play important roles in the disease progression of AD. In the present study, MN‐08, a novel memantine nitrate, was found to inhibit Aβ accumulation, prevent neuronal and dendritic spine loss, and consequently attenuate cognitive deficits in 2‐month‐old APP/PS1 transgenic mice (for a 6‐month preventative course) and in the 8‐month‐old triple‐transgenic (3×Tg‐AD) mice (for a 4‐month therapeutic course). In vitro, MN‐08 could bind to and antagonize NMDA receptors, inhibit the calcium influx, and reverse the dysregulations of ERK and PI3K/Akt/GSK3β pathway, subsequently preventing glutamate‐induced neuronal loss. In addition, MN‐08 had favorable pharmacokinetics, blood‐brain barrier penetration, and safety profiles in rats and beagle dogs. These findings suggest that the novel memantine nitrate MN‐08 may be a useful therapeutic agent for AD. 相似文献
Infants often experience complementary food-induced diarrhoea (CFID), which occurs when infants switch from breast milk to solid foods. The relative abundances of Prevotella and Rothia were higher in stools of infants with CFID, while the relative abundances of Enterococcus and Escherichia were higher in healthy infants. The abundance of Lactobacillus spp. normally found in breast milk fed to infants with CFID was significantly reduced, and Enterococcus spp. were less abundant when diarrhoea occurred. Furthermore, Lactobacillus and Enterococcus were present as shared bacteria in both mother and infant, and they were considered potential anti-CFID probiotics as their relative abundances in breast milk were negatively correlated to infant CFID. Kyoto encyclopedia of genes and genomes (KEGG) functional analysis showed that the function of amino acid metabolism differed between infants with CFID and healthy infants. Therefore, CFID might be related to the decomposition of proteins in food supplements. The screening revealed seven hydrolytic casein and five hydrolytic casein and rice protein isolates from 320 suspected Lactobacillus and Enterococcus isolates. The animal experiments demonstrated that a mixture of five isolates effectively hydrolysed the casein and rice protein and prevented diarrhoea in young rats. Thus, the occurrence of CFID was found to be closely related to the intestinal and breast milk microbiota, and bacteria that could assist in the digestion of cereal proteins were involved in CFID. 相似文献