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Stroke is a serious disease caused by the rupture or blockage of the cerebrovascular system. Its pathogenesis is complex and involves multiple mechanisms. Iristectorin B is a natural isoflavone that has certain anti stroke effects. In this study, an in vitro stroke injury model of glyoxylate deprivation was established using PC12 cells, which was used to evaluate the anti-stroke activity of Iristectorin B in ejecta stem. The results showed that Iristectorin B, a natural isoflavone derived from Dried Shoot, significantly reduced the damage to PC12 cells caused by oxygen glucose deprivation/reoxygenation, decreased apoptosis, enhanced cell survival and reduced Ca2+, LDH and ROS levels. The results showed that Iristectorin B had a significant protective effect on Na2S2O4-injured PC12 cells, and the mechanism may be related to the protective effect of neurons in the brain. After protein extraction and various analyses were performed, a series of cutting-edge technologies were organically combined to study the quantitative proteome of each group. Differential proteins were then analyzed. According to the protein screening principle, ferroptosis-related proteins were most closely associated with stroke. The differential proteins associated with ferroptosis screened were SLC3A2, TFR1 and HMOX1, with HMOX1 being the most significantly elevated and reduced via dosing. Iristectorin B may act as a protective agent against stroke by regulating ferroptosis, and SLC3A2, TFR1 and HMOX1 may serve as potential diagnostic biomarkers for stroke, providing additional evidence to support the importance of ferroptosis in stroke. [ABSTRACT FROM AUTHOR]

Daidzein is a plant isoflavonoid primarily isolated from Pueraria lobate Radix as the dry root of P. lobata (Wild.) Ohwi, have long been used as nutraceutical and medicinal herb in China. Despite the report that daidzein can prevent neuronal damage and improve outcome in experimental stroke, the mechanisms of this neuroprotective action have been not fully elucidated. The aim of this study was to determine whether the daidzein elicits beneficial actions in a stroke model, namely, cerebral ischemia/reperfusion (I/R) injury, and to reveal the underlying neuroprotective mechanisms associated with the regulation of Akt/mTOR/BDNF signal pathway. The results showed that I/R, daidzein treatment significantly improved neurological deficits, infarct volume, and brain edema at 20 and 30 mg/kg, respectively. Meanwhile, it was found out that the pretreatment with daidzein at 20 and 30 mg/kg evidently improved striatal dopamine and its metabolite levels. In addition, daidzein treatment reduced the cleaved Caspase-3 level but enhanced the phosphorylation of Akt, BAD and mTOR. Moreover, daidzein at 30 mg/kg treatment enhanced the expression of BDNF and CREB significantly. This protective effect of daidzein was ameliorated by inhibiting the PI3K/Akt/mTOR signaling pathway using LY294002. To sum up, our results demonstrated that daidzein could protect animals against ischemic damage through the regulation of the Akt/mTOR/BDNF channel, and the present study may facilitate the therapeutic research of stroke. [ABSTRACT FROM AUTHOR]

In the present study, the anti‐inflammation effect of Phellinus igniarius extract was detected on an in vitro model of RAW 264.7 cells stimulated using sodium urate. In this cell model, the content changes of inflammatory cytokines, intercellular adhesion molecule‐1, and interleukin‐1 beta, in cell culture supernatants were detected using an enzyme‐linked immunosorbent assay. The xanthine oxidase inhibitory activity of P. igniarius extracts was determined using a microplate reader. Furthermore, in order to identify the active compounds of P. igniarius, ultrafiltration liquid chromatography mass spectrometry was utilized to screen xanthine oxidase inhibitors from the extract. Our results showed that in the presence of P. igniarius extract, the expressions of interleukin‐1 beta and intercellular adhesion molecule‐1 decreased (p < 0.01 and p < 0.05, respectively) compared to that in the control group. The extract effective inhibited the xanthine oxidase activity. Finally, seven compounds were screened and identified as potential xanthine oxidase inhibitors from P. igniarius. Taken together, these results demonstrate a potential anti‐inflammation bioactivity of P. igniarius in vitro, providing a basis for further in vivo research for the prevention and treatment of gout. [ABSTRACT FROM AUTHOR]

Objectives: To quantitatively evaluate the volume of the ischemic penumbra using susceptibility-weighted imaging and mapping (SWIM) of asymmetrical prominent cortical veins (APCVs) in patients with acute ischemic stroke. Methods: Eighty-five eligible patients with acute ischemic stroke on admission within 12 h from symptom onset were studied. The APCVs on SWIM were quantitatively (SWI-volume) and semi-quantitatively (SWI-Alberta Stroke Program Early CT Score, SWI-ASPECTS) evaluated to calculate mismatch. To assess the diagnostic efficacy of APCVs on SWIM, comparative analyses were performed between SWIvolume-DWI mismatch and SWIASPECTS-DWI mismatch, using PWI-DWI mismatch as a reference. Correlations were calculated between the mismatches, as well as between SWI-volume and time-to-maximum (Tmax) > 6 s volume. Additionally, each of these mismatches was correlated with the National Institute of Health Stroke Scale (NIHSS). Results: The sensitivity, negative predictive value, and accuracy of SWIvolume-DWI mismatch were demonstrably higher than SWIASPECTS-DWI mismatch (100% vs. 53.7%, 100% vs. 9.5%, 97.7% vs. 54.5%, respectively). A significant positive correlation was found between SWIvolume-DWI and PWI-DWI mismatch (r = 0.691, p < 0.01), as well as between SWI-volume and Tmax > 6 s volume (r = 0.786, p < 0.001). A significant negative correlation was found between SWIvolume-DWI mismatch and NIHSS (r = − 0.360, p = 0.022), as well as between SWIASPECTS-DWI mismatch and NIHSS (r = − 0.499, p = 0.001). Conclusions: SWIvolume-DWI mismatch had higher diagnostic efficacy than SWIASPECTS-DWI mismatch in defining the ischemic penumbra and showed good consistency with PWI-DWI mismatch in acute ischemic stroke. Quantitation of APCVs using SWIM provided an accurate method for determining hypoperfusion and provided a reliable method to reflect the hypoxia of penumbra. Key Points: • SWIvolume-DWI mismatch has higher diagnostic efficacy than SWIASPECTS-DWI mismatch in defining the ischemic penumbra. • SWIvolume-DWI mismatch shows good consistency with PWI-DWI mismatch in managing penumbra in acute ischemic stroke. • Quantitation of APCV volume using SWIM provided an accurate method for determining the hypoperfusion area and provided a reliable method to reflect the hypoxia of penumbra. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate differential characteristics of plaque in the middle cerebral artery (MCA) and hemodynamics in patients with ischemic stroke and transient ischemic attack (TIA), and to develop a predictive model for the presence of ischemic stroke and neurological impairment. Methods: Sixty-seven patients with acute ischemic events in MCA territory who underwent high-resolution vessel wall imaging between September 2016 and August 2018 were reviewed retrospectively. Patients were assigned to either the stroke group or TIA group, according to diffusion-weighted imaging and neurological examination. Plaque characteristics and anterograde score (AnS) were calculated. Tmax > 6.0-s volume was acquired by RApid Processing of perfusIon and Diffusion software. Multivariate logistic regression analysis and multiple linear regression analysis were performed to establish a predictive model for irreversible infarction occurrence and clinical severity. Results: Forty-five patients were assigned to the stroke group, and 22 were assigned to the TIA group. Plaque length, intraplaque hemorrhage (IPH), enhancement, AnS, and Tmax > 6.0-s volumes were significantly different between the two groups (p < 0.05). IPH and AnS were independent predictors for patients with stroke (p = 0.020 and 0.034, respectively). Tmax > 6.0-s volume, IPH, hypertension, and AnS were associated with high National Institutes of Health Stroke Scale (NIHSS) scores (all p < 0.05, R = 0.725, and adjusted R2 = 0.494). Conclusions: IPH and AnS are useful in predicting stroke occurrence. Tmax > 6.0-s volume, IPH, hypertension, and AnS are associated with neurological impairment of the patients. Key Points: • Ischemic stroke and TIA patients have different plaque characteristics and hemodynamics. • Intraplaque hemorrhage and anterograde score have high diagnostic efficiency for ischemic stroke. • The combination of Tmax > 6.0-s volume, intraplaque hemorrhage, hypertension, and anterograde score can predict the National Institutes of Health Stroke Scale scores of patients. [ABSTRACT FROM AUTHOR]

Okanin is a major flavonoid found in Coreopsis tinctoria Nutt., arousing huge interest recently for its considerable biological characteristics including antioxidant, antineurotoxic, and antidiabetic activities. An ultrahigh performance liquid chromatography triple-quadrupole tandem mass spectrometry (UPLC-MS) was successfully used to determine okanin in rat plasma after oral administration of okanin. Bavachalcone acted as an internal standard (IS). By gradient elution, IS and analyte were separated on a C18 column for 7 min at a flow rate of 0.25 mL/min with acetonitrile-0.1% acetic acid mobile phase. The stability, matrix effect, extraction recovery, accuracy, precision, linearity, and selectivity of the method were firstly demonstrated. The major pharmacokinetic parameters of okanin in rat plasma were then measured using the developed UPLC-MS method. An UPLC-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was finally established to obtain the specific and accurate mass of okanin in rat plasma after oral administration, and its proposed fragmentation was further elaborated. [ABSTRACT FROM AUTHOR]

In this work, a commercial foldable display of 8.0‐inch 2K AMOLED(Active Matrix Organic Light‐emitting Diode) was developed for foldable smart phones. By considering commercial requirements for a brand new product, fundamental performances are introduced. By new design concepts, display and touch performances are guaranteed, while the foldable reliabilities are also achieved to a commercial goal. Not only how to improve the bending abilities, but also the mechanical abilities of foldable display module are discussed. In bending performance, the endurance of dynamic folding and static folding are treated by different ways. The materials and layer stacks optimization are discussed. The root causes of the deformation in foldable display are analyzed. Solutions for the out‐folding display is suggested. [ABSTRACT FROM AUTHOR]

Superoxide anion radical scavenger and xanthine oxidase inhibitor play an important role in the treatment of several relevant human diseases. In the present study, ultrafiltration liquid chromatography–mass spectrometry coupled to microplate reader was applied to screen and identify superoxide anion radical scavengers and xanthine oxidase inhibitors from total flavonoids of Ginkgo biloba leaves. As a result, four compounds (quercetin, apigenin, kaempferol and isorhamnetin) were screened as xanthine oxidase inhibitors by ultrafiltration LC–MS, and the 50% scavenging concentration values of the screened flavonoids were lower than those for allopurinol. Lineweaver–Burk plot results indicated that kaempferol was a competitive xanthine oxidase inhibitor; the other flavonoids were all anticompetitive inhibitors. Four flavonoids—rutin, quercetin, kaempferol and isorhamnetin—were screened as superoxide anion radical scavengers by LC–MS. The results demonstrate that the method for screening and evaluation of superoxide anion radical scavenger and xanthine oxidase inhibitor from a complex mixture system is feasible and efficient. [ABSTRACT FROM AUTHOR]

Natural products have become one of the most important resources for discovering novel xanthine oxidase inhibitors, which are commonly employed in the treatment of hyperuricemia and gout. However, to date, few reports exist regarding the use of monoterpene glycosides as xanthine oxidase inhibitors. Thus, we herein report the use of ultrafiltration coupled with liquid chromatography in the screening of monoterpene glycoside xanthine oxidase inhibitors from the extract of Paeonia lactiflora ( P. lactiflora), and both high-performance counter-current chromatography and medium-pressure liquid chromatography were employed to separate the main constituents. Furthermore, the xanthine oxidase inhibitory activities and the mechanisms of inhibition of the isolated compounds were evaluated using a multi-mode microplate reader by Molecular Devices. As a result, three monoterpene glycosides were separated by combined high-performance counter-current chromatography and medium-pressure liquid chromatography in purities of 90.4, 98.0, and 86.3%, as determined by liquid chromatography. These three compounds were identified as albiflorin, paeoniflorin, and 1- O-β-ᴅ-glucopyranosyl-8- O-benzoylpaeonisuffrone by electrospray ionization tandem mass spectrometry, and albiflorin and paeoniflorin were screened as potential xanthine oxidase inhibitors by ultrafiltration with liquid chromatography. The evaluation results of xanthine oxidase inhibitory activity corresponded with the screening results, as only albiflorin and paeoniflorin exhibited xanthine oxidase inhibitory activity. [ABSTRACT FROM AUTHOR]

Early hearing deprivation could affect the development of auditory, language, and vision ability. Insufficient or no stimulation of the auditory cortex during the sensitive periods of plasticity could affect the function of hearing, language, and vision development. Twenty-three infants with congenital severe sensorineural hearing loss (CSSHL) and 17 age and sex matched normal hearing subjects were recruited. The amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo) of the auditory, language, and vision related brain areas were compared between deaf infants and normal subjects. Compared with normal hearing subjects, decreased ALFF and ReHo were observed in auditory and language-related cortex. Increased ALFF and ReHo were observed in vision related cortex, which suggest that hearing and language function were impaired and vision function was enhanced due to the loss of hearing. ALFF of left Brodmann area 45 (BA45) was negatively correlated with deaf duration in infants with CSSHL. ALFF of right BA39 was positively correlated with deaf duration in infants with CSSHL. In conclusion, ALFF and ReHo can reflect the abnormal brain function in language, auditory, and visual information processing in infants with CSSHL. This demonstrates that the development of auditory, language, and vision processing function has been affected by congenital severe sensorineural hearing loss before 4 years of age. [ABSTRACT FROM AUTHOR]

Hydroxyl radicals are the most reactive free radical of human body, a strong contributor to tissue damage. In this study, liquid chromatography coupled to electrospray ionization mass spectrometry was applied to screen and identify hydroxyl radical scavengers from the total flavonoids of Ginkgo biloba leaves, and high-performance counter current chromatography was used to separate and isolate the active compounds. Furthermore, molecular devices were used to determine hydroxyl radical scavenging activities of the obtained hydroxyl radical scavengers and other flavonoids from G. biloba leaves. As a result, six compounds were screened as hydroxyl radical scavengers, but only three flavonoids, namely, rutin, cosmos glycosides and apigenin-7- O-Glu-4'- O-Rha, were isolated successfully from total flavonoids by high-performance counter current chromatography. The purities of the three obtained compounds were over 90%, respectively, as determined by liquid chromatography. Molecular devices with 96-well microplates evaluation indicated that the 50% scavenging concentration values of screened compounds were lower than that of other flavonoids, they performed greater hydroxyl radical scavenging activity, and the evaluation effects were consistent with the liquid chromatography with mass spectrometry screening results. Therefore, chromatography combined with molecular devices is a feasible and an efficient method for systematic screening, identification, isolation, and evaluation of bioactive components in mixture of botanical medicines. [ABSTRACT FROM AUTHOR]

Drug resistance remains a significant challenge in the treatment of triple-negative breast cancer (TNBC). Recent studies have demonstrated that this drug resistance is associated with a group of cells known as cancer stem cells (CSCs), which are believed to determine the sensitivity of tumor cells to cancer treatment. MicroRNAs (miRNAs) are small, non-coding RNAs that play significant roles in normal and cancer cells. MiR-223 reportedly acts as a tumor suppressor in a range of cancers. However, the role of miR-223 in TNBC, especially in triple-negative breast cancer stem cells (TNBCSCs), remains unknown. Here, we found that miR-223 expression was down-regulated in CD44+CD24-/low TNBCSCs compared with non-CSCs. Furthermore, we found that miR-223 overexpression resensitized TNBCSCs to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. The HAX-1 gene, which is located in the mitochondria and functions as an anti-apoptotic protein, was found to be directly regulated by miR-223 in MDA-MB-231 cells. We demonstrated that miR-223 overexpression promoted TRAIL-induced apoptosis through the mitochondria/ROS pathway. In conclusion, our results suggest that miR-223 increases the sensitivity of TNBCSCs to TRAIL-induced apoptosis by targeting HAX-1. Our findings have improved our understanding of the role of miR-223 in TNBC and may contribute to TNBC treatment. [ABSTRACT FROM AUTHOR]

MicroRNAs are small non-coding RNAs that may also function as oncogenes and tumor suppressor genes, as the abnormal expression of microRNAs is associated with various human tumors. MicroRNA-145 (miR-145) inhibits growth and increases chemo- or radiosensitivity in various cancers. However, the role of miR-145 in breast cancer progression remains unknown. In this study, miR-145 expression level was measured via quantitative real-time PCR in 88 pairs of human breast cancer tissues and adjacent normal tissues and in a panel of human breast cancer cell lines. Cell proliferation and cell migration were assessed by cell viability assay and transwell assay. Western blot was used to verify Rho-associated protein kinase 1 (ROCK1) as a novel target gene of miR-145. Our results showed that miR-145 was frequently downregulated in breast cancer tissues and cell lines. Overexpression of miR-145 in MCF-7 and BT-549 cell lines significantly inhibited cell proliferation, migration, and invasion in vitro. ROCK1 was identified as a target of miR-145, and ectopic expression of miR-145 downregulated ROCK1. Our findings indicate that miR-145 acts as a tumor suppressor and its downregulation in tumor tissues may contribute to the progression of breast cancer through a mechanism involving ROCK1, suggesting miR-145 as a potential new diagnostic and therapeutic target for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

In the present study, we investigated the protective mechanism of paeoniflorin (PF), a monoterpene glycoside extracted from Radix Paeoniae alba roots, on MPP-induced neurotoxicity in cultured rat pheochromocytoma cells (PC12). Our work included examination of cell viability assessment, amounts of released lactic dehydrogenase (LDH), intracellular Ca concentration, cell apoptosis, mitochondrial membrane potential, caspase-3 activity, and expression profiling of two apoptosis-related genes ( Bcl- 2 and Bax). It was shown that, PF functioned as an MPP antagonist, being able to suppress apoptosis, decrease LDH release and Ca concentration, attenuate membrane potential collapse and, inhibit caspase-3 activation, decrease in Bax/Bcl-2 ratio. These observations suggest that PF could protect PC12 cells against MPP-induced injury and the mechanism PF's neuroprotective effect was closely associated with Bcl-2 up-regulation and Bax down-regulation. PF has neuroprotective effects on MPP-induced apoptosis in PC12 cells via regulating mitochondrial membrane potential and Bcl-2/Bax/caspase-3 signaling pathways, and this new insight will help develop a PF-based therapeutic strategy for treatmenting neurodegenerative diseases and injury. [ABSTRACT FROM AUTHOR]

Context: Mogroside V, a compound isolated from Momordica grosvenori Swingle, which belongs to the Cucurbitaceae, is a traditional Chinese medicine reported to have anti-inflammatory potential in murine macrophages and a murine ear edema model. Objective: To investigate the effects and mechanisms of action of this compound in a model of acute lung injury (ALI) induced by lipopolysaccharides (LPS). Materials and methods: Female BALB/c mice were treated with commercial mogroside V (2.5, 5 and 10 mg/kg) for 1 h prior to intranasal injection of LPS (10 μg in 50 μl). After 12 h, airway inflammation in the ALI model was determined by the wet/dry weight (W/D) ratio, myeloperoxidase (MPO) activity of lung tissue, leukocyte recruitment and cytokine levels in the bronchoalveolar lavage fluid (BALF). Additionally, lung tissue was examined by histology and western blotting to investigate the changes in pathology and the signalling in the presence and absence of mogroside V. Results: Mogroside V at 5 and 10 mg/kg inhibited airway inflammation induced by LPS as measured by the decrease in the histological changes (44 and 67.3% reduction in lung injury score, respectively), a 28.9 and 55.3% reduction in lung MPO activity, and inflammatory cell counts, interleukin-1β (IL-1β, 382 and 280 pg/ml, respectively), IL-6 (378 and 232 pg/ml, respectively) and tumor necrosis factor-α (TNF-α, 12.5 and 7.8 ng/ml, respectively) levels in the BALF. Additionally, mogroside V treatment reduced the activation of cyclooxygenase 2 (COX-2), inducible NO synthase (iNOS), and the nuclear factor (NF)-κB. Discussions and conclusions: Together, these data suggest that mogroside V has the potential to protect against LPS-induced airway inflammation in a model of ALI. [ABSTRACT FROM AUTHOR]

In this study, an accurate and reliable method of ultra‐performance liquid chromatography coupled with a triple‐quadrupole tandem mass spectrometry was firstly developed and fully validated for the simultaneous determination of epicatechin, neoastilbin, astilbin, isoastilbin, engeletin and resveratrol in rat plasma after administration of Smilacis glabrae Roxb. extract. Naringenin was used as an internal standard (IS). The analyte and IS were separated on a C18 column by gradient elution with a mobile phase of acetonitrile–0.3% acetic acid at a flow rate of 0.25 mL/min for a total run time of 8 min. The method was validated in terms of selectivity, linearity, precision, accuracy, extraction recovery, matrix effect and stability. The developed method was successfully applied to determine the main pharmacokinetic parameters of six components in rat plasma. [ABSTRACT FROM AUTHOR]