Clinical Features and Risk Factors of Postoperative Stroke in Adult Moyamoya Disease.

BACKGROUND AND PURPOSE: The clinical features of and risk factors for postoperative stroke after surgical revascularization in adult moyamoya disease (MMD) have not been fully elucidated. To this end, the baseline clinical features were hereby described, and the risk factors for postoperative stroke were determined. METHODS: Data of 4078 MMD inpatients were collected retrospectively across all secondary- and higher-level hospitals of Hubei Province from January 2019 to December 2020. In accordance with inclusion and exclusion criteria, 559 adult MMD inpatients were finally enrolled. The associated characteristics and potential risk factors were analyzed, and the Kaplan-Meier risk of stroke was also calculated. RESULTS: The patients consisted of 286 females and 273 males, with a mean age of 49.1 ± 10.0 years, all of whom had at least 1 year of follow-up (median 25.1 months). There were 356 cases of preoperative ischemic symptoms and 203 cases of preoperative hemorrhage symptoms. Indirect, direct, and combined revascularization were conducted on 97, 105 and 357 patients, respectively. Among these patients, 17 had postoperative hemorrhagic stroke (PHS), and 43 had postoperative ischemic stroke (PIS). A comparison between PHS/PIS group and control group (patients without postoperative stroke events) showed that preoperative hemorrhage was significantly associated with PHS (p = 0.003), while hypertension (p = 0.003), diabetes mellitus (p = 0.003) and modified Rankin scale (mRS) (p = 0.034) at admission were associated with a higher rate of PIS. Furthermore, preoperative hemorrhagic stroke was identified as a risk factor for PHS (odds ratio [OR], 4.229 [95% CI, 1.244-14.376]; p = 0.021), while hypertension (odds ratio [OR], 0.424 [95% CI, 0.210-0.855]; p = 0.017), diabetes mellitus (odds ratio [OR], 0.368 [95% CI, 0.163-0.827]; p = 0.016) and admission mRS (odds ratio [OR], 2.301 [95% CI, 1.157-4.575]; p = 0.017) were found to be risk factors for PIS. CONCLUSIONS: The age distribution of adult MMD patients with revascularization was predominantly concentrated within the range from 46 to 55 years. Preoperative hemorrhage events were considered the risk factor for PHS. Hypertension, diabetes and admission mRS were correlated with PIS, and were also the risk factors for PIS. These results indicated the possible contribution of enhancing systematic disease management to the prevention of postoperative cerebrovascular accidents.

Genome-Wide 5-Formylcytosine Redistribution in KCl-Stimulated Mouse Primary Cortical Neurons is Associated with Neuronal Activity.

An abundant accumulation of DNA demethylation intermediates has been identified in mammalian neurons. While the roles of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in neuronal function have been extensively studied, little is known about 5-formylcytosine (5fC) in neurons. Therefore, this study was to investigate the genome-wide distribution and potential functions of 5fC in neurons. In an in vitro culture model of mouse primary cortical neurons, we observed a dynamic increase in the total 5fC level in the neuronal genome after potassium chloride (KCl) stimulation. Subsequently, we employed chemical-labeling-enabled C-to-T conversion sequencing (CLEVER-seq) to examine the 5fC distribution at a single-base resolution. Bioinformatic analysis revealed that 5fC was enriched in promoter regions, and gene ontology (GO) analysis indicated that the differential formylation positions (DFP) were correlated with neuronal activities. Additionally, integration with previously published nascent RNA-seq data revealed a positive correlation between gene formylation and mRNA expression levels. As well, 6 neuro-activity-related genes with a positive correlation were validated. Furthermore, we observed higher chromatin accessibility and RNA pol II binding signals near the 5fC sites through multiomics analysis. Motif analysis identified potential reader proteins for 5fC. In conclusion, our work provides a valuable resource for studying the dynamic changes and functional roles of 5fC in activated mammalian neurons.

KD_ConvNeXt: knowledge distillation-based image classification of lung tumor surgical specimen sections.

Introduction: Lung cancer is currently among the most prevalent and lethal cancers in the world in terms of incidence and fatality rates. In clinical practice, identifying the specific subtypes of lung cancer is essential in diagnosing and treating lung lesions. Methods: This paper aims to collect histopathological section images of lung tumor surgical specimens to construct a clinical dataset for researching and addressing the classification problem of specific subtypes of lung tumors. Our method proposes a teacher-student network architecture based on a knowledge distillation mechanism for the specific subtype classification of lung tumor histopathological section images to assist clinical applications, namely KD_ConvNeXt. The proposed approach enables the student network (ConvNeXt) to extract knowledge from the intermediate feature layers of the teacher network (Swin Transformer), improving the feature extraction and fitting capabilities of ConvNeXt. Meanwhile, Swin Transformer provides soft labels containing information about the distribution of images in various categories, making the model focused more on the information carried by types with smaller sample sizes while training. Results: This work has designed many experiments on a clinical lung tumor image dataset, and the KD_ConvNeXt achieved a superior classification accuracy of 85.64% and an F1-score of 0.7717 compared with other advanced image classification methods.

Treatment of moyamoya disease with intracranial aneurysm by surgical clipping combined with encephalo-duro-myo-synangiosis surgery: a case report and literature review.

BACKGROUND: We report a case of 39-year-old male patient with an unruptured middle cerebral artery aneurysm associated with moyamoya disease (MMD) treated by surgical clipping combined with encephalo-duro-myo-synangiosis surgery. CASE DESCRIPTION: A 39-year-old male patient with a history of intraventricular hemorrhage was admitted to our hospital. Preoperative digital subtraction angiography (DSA) showed the aneurysm, arising from a collateral branch of the right middle cerebral artery (RMCA), had an extremely thin neck. Also present were an occlusion of the RMCA main trunk, and moyamoya vessels. Microsurgical aneurysm clipping was performed for the aneurysm, while encephalo-duro-myo-synangiosis was performed for ipsilateral MMD. At the 4-month follow-up, the patient had recovered well and DSA indicated improved cerebral perfusion with no de novo aneurysms. CONCLUSIONS: For ipsilateral moyamoya disease accompanied with intracranial aneurysm (IA), simultaneous surgery combining microsurgical clipping and encephalo-duro-myo-synangiosis can be a good treatment option.

Rapid, automated, and experimenter-free touchscreen testing reveals reciprocal interactions between cognitive flexibility and activity-based anorexia in female rats.

Anorexia nervosa has among the highest mortality rates of any psychiatric disorder and is characterized by cognitive inflexibility that persists after weight recovery and contributes to the chronic nature of the condition. What remains unknown is whether cognitive inflexibility predisposes individuals to anorexia nervosa, a question that is difficult to address in human studies. Our previous work using the most well-established animal model of anorexia nervosa, known as activity-based anorexia (ABA) identified a neurobiological link between cognitive inflexibility and susceptibility to pathological weight loss in female rats. However, testing flexible learning prior to exposure to ABA in the same animals has been thus far impossible due to the length of training required and the necessity of daily handling, which can itself influence the development of ABA. Here, we describe experiments that validate and optimize the first fully-automated and experimenter-free touchscreen cognitive testing system for rats and use this novel system to examine the reciprocal links between reversal learning (an assay of cognitive flexibility) and weight loss in the ABA model. First, we show substantially reduced testing time and increased throughput compared to conventional touchscreen testing methods because animals engage in test sessions at their own direction and can complete multiple sessions per day without experimenter involvement. We also show that, contrary to expectations, cognitive inflexibility measured by this reversal learning task does not predispose rats to pathological weight loss in ABA. Instead, rats that were predisposed to weight loss in ABA were more quickly able to learn this reversal task prior to ABA exposure. Intriguingly, we show reciprocal links between ABA exposure and cognitive flexibility, with ABA-exposed (but weight-recovered) rats performing much worse than ABA naïve rats on the reversal learning task, an impairment that did not occur to the same extent in rats exposed to food restriction conditions alone. On the other hand, animals that had been trained on reversal learning were better able to resist weight loss upon subsequent exposure to the ABA model. We also uncovered some stable behavioral differences between ABA susceptible versus resistant rats during touchscreen test sessions using machine learning tools that highlight possible predictors of anorectic phenotypes. These findings shed new light on the relationship between cognitive inflexibility and pathological weight loss and provide targets for future studies using the ABA model to investigate potential novel pharmacotherapies for anorexia nervosa.

Integrated insight into the molecular mechanisms of selenium-modulated, MPP+-induced cytotoxicity in a Parkinson's disease model.

OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disease that is associated with oxidative stress. Due to the anti-inflammatory and antioxidant functions of Selenium (Se), this molecule may have neuroprotective functions in PD; however, the involvement of Se in such a protective function is unclear. METHODS: 1-methyl-4-phenylpyridinium (MPP+), which inhibits mitochondrial respiration, is generally used to produce a reliable cellular model of PD. In this study, a MPP+-induced PD model was used to test if Se could modulate cytotoxicity, and we further capture gene expression profiles following PC12 cell treatment with MPP+ with or without Se by genome wide high-throughput sequencing. RESULTS: We identified 351 differentially expressed genes (DEGs) and 14 differentially expressed long non-coding RNAs (DELs) in MPP+-treated cells when compared to controls. We further document 244 DEGs and 27 DELs in cells treated with MPP+ and Se vs. cells treated with MPP+ only. Functional annotation analysis of DEGs and DELs revealed that these groups were enriched in genes that respond to reactive oxygen species (ROS), metabolic processes, and mitochondrial control of apoptosis. Thioredoxin reductase 1 (Txnrd1) was also identified as a biomarker of Se treatment. CONCLUSIONS: Our data suggests that the DEGs Txnrd1, Siglec1 and Klf2, and the DEL AABR07044454.1 which we hypothesize to function in cis on the target gene Cdkn1a, may modulate the underlying neurodegenerative process, and act a protective function in the PC12 cell PD model. This study further systematically demonstrated that mRNAs and lncRNAs induced by Se are involved in neuroprotection in PD, and provides novel insight into how Se modulates cytotoxicity in the MPP+-induced PD model.

A Preliminary Study of Immediate Intraperitoneal Chemotherapy for Stage III Colorectal Cancer.

OBJECTIVES: Investigate the survival of patients with stage III colorectal cancer (CRC) treated with immediate postoperative intraperitoneal chemotherapy. METHODS: The clinical data of 195 patients with stage III CRC admitted to The First Affiliated Hospital of Wenzhou Medical University from June 2017 to June 2018 were retrospectively analyzed. The patients were divided into an observation group and a control group, both groups were treated with the routine laparoscopic radical operation, on the basis of which, the patients in the observation group were treated with intraperitoneal perfusion chemotherapy during the operation. The local recurrence, abdominal cavity metastasis, and liver metastasis were followed up, and the time of disease recurrence and total survival were recorded. RESULTS: The survival analysis showed that there was a significant difference in progression-free survival (χ 2 = 5.416, P = 0.020) and overall survival (χ 2 = 4.673, P = 0.031) between the observation group and the control group. CONCLUSIONS: During laparoscopic radical resection of CRC, the use of intraperitoneal chemotherapy with raltitrexed can achieve satisfactory results and improve the survival rate of patients with stage III CRC, perioperative use of raltitrexed has been shown to be beneficial in terms of overall survival and progression-free survival.

ZrO2 coated Li1.9K0.1ZnTi3O8 as an anode material for high-performance lithium-ion batteries.

The Li1.9K0.1ZnTi3O8@ZrO2 (1 wt%, 3 wt%, and 5 wt%) anode material was synthesized by doping Li2ZnTi3O8 with potassium and coating ZrO2, where the ZrO2 coating layer was prepared by citric acid and zirconium acetate, and the potassium source was KCl. When the added ZrO2 amount is 3%, the material has the most uniform size, reduced polarization, and reduced charge transfer resistance, and the specific capacity of LKZTO@ZrO2 (3 w%) was 361.5 mA h g-1 at 200 mA g-1 at the 100th cycle, which is higher than that of LKZTO, of 311.3 mA h g-1. The specific capacities of LKZTO@ZrO2 (3 w%) at 50, 100, 200, 500, and 1000 mA g-1 after 10 cycles were 424.9, 410.7, 394.1, 337.6 and 270.6 mA h g-1, indicating that LKZTO@ZrO2 (3 w%) has excellent electrochemical performance.

Single-cell and WGCNA uncover a prognostic model and potential oncogenes in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Single-cell transcriptome sequencing (scRNA-seq) can provide accurate gene expression data for individual cells. In this study, a new prognostic model was constructed by scRNA-seq and bulk transcriptome sequencing (bulk RNA-seq) data of CRC samples to develop a new understanding of CRC. METHODS: CRC scRNA-seq data were downloaded from the GSE161277 database, and CRC bulk RNA-seq data were downloaded from the TCGA and GSE17537 databases. The cells were clustered by the FindNeighbors and FindClusters functions in scRNA-seq data. CIBERSORTx was applied to detect the abundance of cell clusters in the bulk RNA-seq expression matrix. WGCNA was performed with the expression profiles to construct the gene coexpression networks of TCGA-CRC. Next, we used a tenfold cross test to construct the model and a nomogram to assess the independence of the model for clinical application. Finally, we examined the expression of the unreported model genes by qPCR and immunohistochemistry. A clone formation assay and orthotopic colorectal tumour model were applied to detect the regulatory roles of unreported model genes. RESULTS: A total of 43,851 cells were included after quality control, and 20 cell clusters were classified by the FindCluster () function. We found that the abundances of C1, C2, C4, C5, C15, C16 and C19 were high and the abundances of C7, C10, C11, C13, C14 and C17 were low in CRC tumour tissues. Meanwhile, the results of survival analysis showed that high abundances of C4, C11 and C13 and low abundances of C5 and C14 were associated with better survival. The WGCNA results showed that the red module was most related to the tumour and the C14 cluster, which contains 615 genes. Lasso Cox regression analysis revealed 8 genes (PBXIP1, MPMZ, SCARA3, INA, ILK, MPP2, L1CAM and FLNA), which were chosen to construct a risk model. In the model, the risk score features had the greatest impact on survival prediction, indicating that the 8-gene risk model can better predict prognosis. qPCR and immunohistochemistry analysis showed that the expression levels of MPZ, SCARA3, MPP2 and PBXIP1 were high in CRC tissues. The functional experiment results indicated that MPZ, SCARA3, MPP2 and PBXIP1 could promote the colony formation ability of CRC cells in vitro and tumorigenicity in vivo. CONCLUSIONS: We constructed a risk model to predict the prognosis of CRC patients based on scRNA-seq and bulk RNA-seq data, which could be used for clinical application. We also identified 4 previously unreported model genes (MPZ, SCARA3, MPP2 and PBXIP1) as novel oncogenes in CRC. These results suggest that this model could potentially be used to evaluate the prognostic risk and provide potential therapeutic targets for CRC patients.

How Can Animal Models Inform the Understanding of Cognitive Inflexibility in Patients with Anorexia Nervosa?

Deficits in cognitive flexibility are consistently seen in patients with anorexia nervosa (AN). This type of cognitive impairment is thought to be associated with the persistence of AN because it leads to deeply ingrained patterns of thought and behaviour that are highly resistant to change. Neurobiological drivers of cognitive inflexibility have some commonalities with the abnormal brain functional outcomes described in patients with AN, including disrupted prefrontal cortical function, and dysregulated dopamine and serotonin neurotransmitter systems. The activity-based anorexia (ABA) model recapitulates the key features of AN in human patients, including rapid weight loss caused by self-starvation and hyperactivity, supporting its application in investigating the cognitive and neurobiological causes of pathological weight loss. The aim of this review is to describe the relationship between AN, neural function and cognitive flexibility in human patients, and to highlight how new techniques in behavioural neuroscience can improve the utility of animal models of AN to inform the development of novel therapeutics.

Downregulation of MiR-1538 promotes proliferation and metastasis of colorectal cancer by targeting DNMT3A.

Colorectal cancer (CRC) is a common malignant tumor of digestive tract, but the molecular mechanism of its occurrence and development is not clear. Some studies have shown that microRNA (miRNA) plays an important role in the occurrence and development of cancer, but many miRNAs which play an important role in the progression of CRC remain to be investigated. In this study，we found that the expression of miR-1538 was significantly down-regulated in CRC tissues and cells, and its expression level was significantly correlated with tumor size, clinical stage and prognosis. Functional and mechanism experiments showed that miR-1538 decreased the protein level of DNA methyltransferases 3A (DNMT3A) and inhibited the proliferation, migration and invasion of CRC cells by targeting the 3'-UTR of DNMT3A mRNA. Our results identify the biological function and mechanism of miR-1538 as a tumor suppressor gene in the progression of CRC, and suggest that miR-1538 can be used as a potential prognostic marker and therapeutic target for CRC.

Asymmetric Cyanosilylation of Aldehydes by a Lewis Acid/Base Synergistic Catalyst of Chiral Metal Clusters.

Metal clusters with well-defined crystal structures are extremely useful for studying the synergistic catalytic effects and associated catalytic mechanisms. In this study, two pairs of chiral lanthanide-transition metal clusters (R)/(S)-Co3Ln2 (Ln = Tb or Dy) were synthesized using Schiff-base ligands [(R)- or (S)-H3L] with multiple Lewis base sites (O sites). The as-prepared (R)/(S)-Co3Ln2 chiral metal clusters exhibited good catalytic functionality in the asymmetric synthesis of chiral cyanohydrins, with high conversions of up to 99% and medium-to-high enantiomeric excess values of up to 78%. The catalysis process followed a mechanism in which the bifunctional metal clusters of (R)/(S)-Co3Ln2, containing Lewis acid sites and Lewis base sites, simultaneously activated the aldehydes and trimethylsilyl cyanide, respectively. Consequently, synergistic catalysis was realized. The enantioselectivity of the different aldehydes and stereochemical configuration of the resulting products are attributed to the formation of a steric chiral pocket via the external chiral ligands on the clusters. In addition, heterogeneous asymmetric cyanosilylation using (R)/(S)-Co3Ln2 chiral metal clusters achieved high chemoselectivity and regioselectivity under mild conditions.

Evaluation of Bone Wax Coated Bipolar Coagulation Forceps: Performance and Safety Assessment.

BACKGROUND: Improving the performance of bipolar coagulation forceps is crucial for safer and more accurate neurosurgery. In our department, we found that bone wax (BW) melted by thermal effect of bipolar electrocoagulation can achieve more efficient hemostasis and reduce the amount of BW in neurosurgical procedures associated with bleeding from emissary and diploic veins. Nevertheless, relevant studies are still lacking to verify our finding. OBJECTIVE: The study objectives were to evaluate the performance and safety in electrocoagulation: (1) compare the performance of BW coated bipolar coagulation forceps and the conventional anti-stick forceps in vivo, and (2) assess the safety of electrocoagulation with BW coated bipolar coagulation forceps in rat primary motor cortex. METHODS: Tissue adhesion was evaluated by comparing the wetting tension and the amount of protein adhered to the forceps tips after electrocoagulation. Thermal damage was assessed by analyzing the thermography and H&E staining of coagulated rat brain tissues. The hemostatic efficiency was reflected by the number of electrocoagulation until complete hemostasis and the condition of damaged common carotid arteries. The safety of BW coated forceps in electrocoagulation was assessed by evaluating the inflammation of coagulated rat primary motor cortex and the motor functions at the 7th day postoperatively. RESULTS: Bone wax coated forceps had a significantly higher contact angle and adhered less coagulum. Thermography was acquired at 3 s, 6 W units in rat primary motor cortex in vivo. The highest temperature recorded during BW coated tips application was significantly lower than the uncoated. In addition, there was a relatively smaller tissue injury area produced by the BW coated forceps. Additionally, BW coated forceps improved the hemostatic efficiency and caused fewer injuries on the damaged arteries (3 s, 10 W units). More importantly, electrocoagulation with BW coated forceps led to no significant motor function impairments and less glial and microglia responses. CONCLUSION: This study reveals that BW coated bipolar coagulation forceps can provide a convenient, cost-efficient, safer, and more efficient way for hemostasis. More research is needed to evaluate the electrocoagulation with BW in the long term and verify our finding in human beings.

Health Care Pollution And Public Health Damage In The United States: An Update.

An up-to-date assessment of environmental emissions in the US health care sector is essential to help policy makers hold the health care industry accountable to protect public health. We update national-level US health-sector emissions. We also estimate state-level emissions for the first time and examine associations with state-level energy systems and health care quality and access metrics. Economywide modeling showed that US health care greenhouse gas emissions rose 6 percent from 2010 to 2018, reaching 1,692 kg per capita in 2018-the highest rate among industrialized nations. In 2018 greenhouse gas and toxic air pollutant emissions resulted in the loss of 388,000 disability-adjusted life-years. There was considerable variation in state-level greenhouse gas emissions per capita, which were not highly correlated with health system quality. These results suggest that the health care sector's outsize environmental footprint can be reduced without compromising quality. To reduce harmful emissions, the health care sector should decrease unnecessary consumption of resources, decarbonize power generation, and invest in preventive care. This will likely require mandatory reporting, benchmarking, and regulated accountability of health care organizations.

Optimization in continuous phase-transition extraction of crude flavonoids from finger citron fruit and evaluation on their antiaging activities.

The development of antiaging functional products is a hot topic in the field of functional foods. However, the efficient extraction of functional ingredients is the limiting step for the functional food industry. Continuous phase-transition extraction (CPE) is a new extraction technique that combines the advantages of Soxhlet extraction and supercritical extraction, which may have a distinct advantage over traditional methods in the extraction of flavonoids. In our study, the Box-Behnken design combined with response surface methodology was used to optimize CPE of crude flavonoids from finger citron fruit. The antiaging activities of finger citron crude flavonoids (FCCF) were evaluated by Caenorhabditis elegans (C. elegans) model. The optimal extraction conditions for CPE were as follows: ethanol concentration 85%, temperature 90°C, time 120 min, and pressure 0.2 MPa. Compared with the heat reflux extraction, the extraction rate and content of FCCF extracted by CPE increased by 24.28% and 33.22% (p < .05), respectively. FCCF extended the lifespan of C. elegans by 14.94% without causing adverse effects on their reproduction and locomotion ability. A further analysis suggested that FCCF prolonged the lifespan of nematodes under normal and oxidative stress by increasing the activity of major enzymes in endogenous antioxidant defense system and reducing the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA). The results confirmed the effectiveness of CPE in extracting crude flavonoids from finger citron fruit, and the extracted FCCF exhibited strong antiaging activities.

PP2Ac upregulates PI3K-Akt signaling and induces hepatocyte apoptosis in liver donor after brain death.

Multiple research groups have demonstrated that the outcome of patients receiving liver grafts from brain death donors (DBD) is poorer when compared with patients receiving grafts from living donors. This might be due to an increased hepatocyte apoptosis induced after brain death (BD). In this work, we found that the activity of PP2A-Akt pathway is significantly increased in clinical donor ex vivo hepatocytes after BD by iTRAQ protein quantification analysis. The same results were confirmed in animal models. A time-dependent promotion of apoptosis was also found in DBD rabbit liver, as demonstrated by the increased levels of cleaved Caspase 3 and the decreased of Bcl-2. To further investigate the roles of PP2A and Akt in regulating apoptosis of hepatocytes after BD, we cultivated human liver cell line L02 with serum deprivation and hypoxia, to simulate the ischemic and hypoxic conditions of hepatocytes in DBD. Increased apoptosis and decreased viability were observed during the time in this model. Meanwhile PP2A activity and Akt activity were respectively increased and decreased. Notably, the proportion of Akt phosphorylation at Ser473 decreased, while other known targets of PP2A (p38, JNK and ERK) were not affected in terms of protein levels or phosphorylation. These results suggested that PP2A is involved in apoptotic induction of hepatocytes after brain death by specific suppression of Akt. This discovery was further confirmed with pharmaceutical and genetic methods. Our work implied potential targets for reducing liver cell apoptosis and improving organ donor quality after BD.

Linking the low-density lipoprotein receptor-binding segment enables the therapeutic 5-YHEDA peptide to cross the blood-brain barrier and scavenge excess iron and radicals in the brain of senescent mice.

INTRODUCTION: Iron accumulates in the brain during aging, which catalyzes radical formation, causing neuronal impairment, and is thus considered a pathogenic factor in Alzheimer's disease (AD). To scavenge excess iron-catalyzed radicals and thereby protect the brain and decrease the incidence of AD, we synthesized a soluble pro-iron 5-YHEDA peptide. However, the blood-brain barrier (BBB) blocks large drug molecules from entering the brain and thus strongly reduces their therapeutic effects. However, alternative receptor- or transporter-mediated approaches are possible. METHODS: A low-density lipoprotein receptor (LDLR)-binding segment of Apolipoprotein B-100 was linked to the 5-YHEDA peptide (bs-5-YHEDA) and intracardially injected into senescent (SN) mice that displayed symptoms of cognitive impairment similar to those of people with AD. RESULTS: We successfully delivered 5-YHEDA across the BBB into the brains of the SN mice via vascular epithelium LDLR-mediated endocytosis. The data showed that excess brain iron and radical-induced neuronal necrosis were reduced after the bs-5-YHEDA treatment, together with cognitive amelioration in the SN mouse, and that the senescence-associated ferritin and transferrin increase, anemia and inflammation reversed without kidney or liver injury. DISCUSSION: bs-5-YHEDA may be a mild and safe iron remover that can cross the BBB and enter the brain to relieve excessive iron- and radical-induced cognitive disorders.

Anti-Inflammatory Effects of Vitisinol A and Four Other Oligostilbenes from Ampelopsis brevipedunculata var. Hancei.

In this study, the cytotoxicities and anti-inflammatory activities of five resveratrol derivatives-vitisinol A, (+)-ε-viniferin, (+)-vitisin A, (-)-vitisin B, and (+)-hopeaphenol-isolated from Ampelopsis brevipedunculata var. hancei were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lipopolysaccharide (LPS)-stimulated RAW264.7 cells, respectively. The result from MTT assay analysis indicated that vitisinol A has lower cytotoxicity than the other four well-known oligostilbenes. In the presence of vitisinol A (5 µM), the significant reduction of inflammation product (nitric oxide, NO) in LPS-induced RAW264.7 cells was measured using Griess reaction assay. In addition, the under-expressed inflammation factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in LPS-induced RAW264.7 cells monitored by Western blotting simultaneously suggested that vitisinol A has higher anti-inflammatory effect compared with other resveratrol derivatives. Finally, the anti-inflammatory effect of vitisinol A was further demonstrated on 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema in mice. As a preliminary functional evaluation of natural product, the anti-inflammatory effect of vitisinol A is the first to be examined and reported by this study.