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Background: Chronic cerebral ischemia (CCI) is a significant health issue characterized by hypoperfusion due to damage or occlusion of the cerebral or carotid arteries. CCI may lead to progressive cognitive impairment that is considered as a prelude to neurodegenerative diseases, including dementia and Alzheimer's disease (AD). Endothelial progenitor cells (EPCs) have been implicated in vascular repair in ischemic cerebrovascular diseases, primarily by differentiating into endothelial cells (ECs) or through paracrine effects. However, the clinical transplantation of stem cell therapies remains limited. In this study, we investigated the effects of EPC-derived conditioned medium (EPC-CM) on the impaired vasculature and neurological function in a rodent model of CCI and the mechanism involved., Methods: EPC-CM was analyzed by cytokine array to identify key factors involved in angiogenesis and cellular senescence. The effects and mechanism of the candidate factors in the EPC-CM were validated in vitro using oxygen-glucose deprivation (OGD)-injured ECs and EPCs. The therapeutic effects of EPC-CM and the identified key factor were further examined in a rat model of CCI, which was induced by bilateral internal carotid artery ligation (BICAL). EPC-CM was administered via intracisternal injection one week post BICAL. The cerebral microvasculature and neurobehavior of the rats were examined three weeks after BICAL., Results: Macrophage migration inhibitory factor (MIF) was identified as a key factor in the EPC-CM. Recombinant MIF protein promoted angiogenesis and prevented senescence in the injured EPCs and ECs. The effect was similar to that of the EPC-CM. These therapeutic effects were diminished when the EPC-CM was co-treated with MIF-specific antibody (Ab). Additionally, the vascular, motor, and cognitive improvements observed in the BICAL rats treated with EPC-CM were abolished by co-treated with MIF Ab. Furthermore, we found MIF promoted angiogenesis and anti-senescence via activating the AKT pathway. Inhibition of the AKT pathway diminished the protective effects of MIF in the in vitro study., Conclusions: We demonstrated that EPC-CM protected the brain from chronic ischemic injury and promoted functional recovery through MIF-mediated AKT pathway. These findings suggest EPC-CM holds potential as a novel cell-free therapeutic approach for treating CCI through the actions of MIF., Competing Interests: Declarations Ethics approval and consent to participate This animal experiments were conducted in accordance with the ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) and was approved by the Institutional Animal Care and Use Committee of National Taiwan University (Approval no. IACUC-20180430, date of approval: 08/01/2019). The EPCs were collected from fresh human umbilical cord blood and was approved by the Institutional Review Board of National Taiwan University Hospital, Taipei, Taiwan (Study title: Platform establishment, validation, and biomarkers study in cerebrovascular diseases: using pediatric moyamoya disease as a pilot. Approval no. IRB-201204074RIC, date of approval: 07/04/2012; Study title: The pathophysiology of indirect revascularization in chronic cerebral ischemia-induced tauopathy: an in vitro, in vivo and clinical study. Approval no. IRB-202012174RIND, date of approval: 01/19/2021). All patients gave written informed consent for participation in the study and the use of samples. Consent for publication All the authors approved this manuscript to be published in the Journal Stem Cell Research & Therapy. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease. Method: This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. The pre- and postoperative rates were compared using the McNeinar χ 2 test. Result: Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged ( M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) ( κ =0.169, P =0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) ( κ =0.170, P =0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn't affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions: Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.

The cardinal electrophysiological signs in Parkinson's disease (PD) include augmented beta oscillations in the motor cortex-subthalamic nucleus (MC-STN) axis and excessive burst discharges in STN. We have shown that excessive STN burst discharges have a direct causal relation with the locomotor deficits in PD. To investigate the correlation between the two cardinal signs, we characterized the courses of development of the electrophysiological abnormalities in the hemiparkinsonian rat model. The loss of dopaminergic neurons develops fast, and is histologically completed within 4-7 days of the lesion. The increase in STN burst discharges is limited to the lesioned side, and follows a very similar course. In contrast, beta augmentation has a bilateral presentation, and requires 14-21 days for full development. Behaviorally, the gross locomotor deficits in open field test and limb akinesia in stepping test match the foregoing fast and slow time courses, respectively. A further look into the spike entrainment shows that the oscillations in local field potential (LFP) of the MC effectively entrain the multi-unit (MU) spikes of MC, STN and entopeduncular nucleus (EPN), a rat homolog of human globus pallidus interna (GPi), whereas the LFP of STN or EPN (GPi) cannot entrain the spikes in MC. We conclude that excessive STN burst discharges are a direct consequence, whereas beta augmentation is probably a secondary or adaptive changes in the cortico-subcortical re-entrant loops, to dopaminergic deprivation. Beta augmentation is therefore not so consistently present as excessive STN burst discharges, but could signal more delicate derangements at the level of cortical programming in PD., (Copyright © 2022. Published by Elsevier Inc.)

Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.

Objective: To investigate the effect of a novel laparoscopic W-H fundoplication in the treatment of proton pump inhibitor (PPI) dependent gastroesophageal reflux disease (GERD). Methods: The clinical data of PPI dependent GERD patients who underwent laparoscopic W-H fundoplication in PLA Rocket Force Characteristic Medical Center from October 1st, 2018 to April 30th, 2019 were analyzed retrospectively. The GERD symptom score, subjective symptom relief, PPI withdrawal, efficacy satisfaction and postoperative complications were followed up and analyzed by a questionnaire. Results: A total of 80 GERD patients were included in this study, and 49 were male and 31 were female, with a median age of 58 years. Among all patients, 85% (68/80) are with esophagitis and 77.5% (62/80) with hiatal hernia. The operation time was 67 (52, 73) minutes, without intraoperative complications and conversion to laparotomy. The postoperative follow-up period was 16 (14, 18) months. The postoperative GERD symptom scores were significantly lower than those before surgery, with an statistical difference (all P <0.05). The subjective remission degree of the overall digestive and respiratory symptoms were 100 (90, 100)% and 100 (80, 100)%, respectively. During the follow-up period, the PPI discontinuation rate was 83% (69/80), and the satisfactory rate was 93% (75/80). Postoperative complications included dysphagia, flatulence, increased exhaust and diarrhea, and the incidence was 61% (49/80), 8% (6/80), 5% (4/80) and 4% (3/80), respectively, and 16% (13/80) of the patients had prolonged occasional mild dysphagia. There was no death, symptomatic recurrence or reoperation. Conclusions: The novel W-H fundoplication has a good medium-term efficacy, with significant GERD symptom control rate and PPI discontinuation rate. The postoperative dysphagia is common, but it is self-limiting and does not affect the satisfaction of the surgical effect.

Background: Particulate matter 2.5 (PM2.5) refers to particulate matter with aerodynamic equivalent diameter less than or equal to 2.5 µm, which is an important component of air pollution. PM2.5 aggravates allergic rhinitis (AR) and promotes AR nasal mucosa inflammation. Therefore, the influence of PM2.5 inhalation exposure on microRNA (miRNA) expression profiles and function in the nasal mucosa of AR rats was investigated., Methods: Female Sprague Dawley rats were distributed randomly to 2 groups: AR model PM2.5 exposure group (ARE group) and AR model PM2.5-unexposed control group (ARC group). The rats of ARE group were made to inhale PM2.5 at a concentration of 200 µg/m 3 , 3 h/day, for 30 days. miRNA expression profiles of the nasal mucosa from both groups were determined using an miRNA gene chip and were verified by quantitative real-time PCR (qRT-PCR). Gene function enrichment analysis was performed using bioinformatics analysis., Results: The ARE group revealed 20 significantly differentially expressed miRNAs, including 4 upregulated and 16 downregulated miRNAs (fold change > 1.5 or < 0.66, P  < .05). Of these, 9 selected miRNAs were verified by qRT-PCR, and the results of 8 miRNAs were in accordance with the miRNA gene chip results, with highly positive correlation ( r  = .8583, P  = .0031). Numerous target genes of differentially expressed miRNAs were functionally enriched in high-affinity immunoglobulin E receptor signaling, ErbB signaling, mucin O-glycans biosynthesis, transforming growth factor β signaling, mitogen-activated protein kinase signal transduction, phosphatidylinositol signaling, mucopolysaccharide biosynthesis, mammalian target of rapamycin signaling, T cell receptor signaling, Wnt signaling, chemokine signal transduction, and natural killer cell-mediated cytotoxicity pathways., Conclusions: PM2.5 causes significant changes in miRNA expression in the nasal mucosa of AR rats. miRNA plays an important role in regulating PM2.5 effects in AR rat biological behavior and mucosal inflammation. This study provides a theoretical basis for the prevention and treatment of AR from the effects of environmental pollution on the gene regulation mechanism.

Objective: To explore the role of autophagy in PM2.5-induced inflammation in human nasal epithelial cells and related mechanism. Methods: Human nasal epithelial cells were exposed to different concentration of PM2.5 for different times, and the expression levels of microtubule-associated protein-1 light chain-3 Ⅱ (LC3 Ⅱ) and Beclin1 proteins were measured by Western blot. The typical autophagosome and autolysosome were observed by using transmission electron microscopy (TEM). To observe autophagic flux, mRFP-GFP-LC3 plasmid was transfected to nasal epithelial cells and the punctate staining of mRFP-GFP-LC3 were determined by confocal laser scanning microscope. The expression of inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in cell culture supernatant were assessed by enzyme-linked immunosorbent assay (ELISA). To assess the role of autophagy in PM2.5-mediated inflammation, autophagy related gene Atg5 and Beclin-1 were silenced by siRNA knockdown, and inflammatory cytokines were analyzed.GraphPad Prism 6.0 was used for statistical analysis. Results: PM2.5 exposure increased the expression of LC3 Ⅱ and Beclin-1 proteins in a dose- (in PM2.5 group with concentration of 0, 15, 30, 60, 120 μg/ml, the expression of LC3 Ⅱ was 0.021±0.001( x ± s ), 0.037±0.002, 0.058±0.005, 0.075±0.006, 0.085±0.004, respectively, F= 126.8, P< 0.05; the expression of Beclin-1 was 0.002±0.000, 0.003±0.000, 0.005±0.000, 0.007±0.001, 0.008±0.001, respectively, F= 137.3, P< 0.05) and time-dependent manner (in PM2.5 group with exposure time of 0, 3, 6, 12, 24 h, the expression of LC3Ⅱ was 0.160±0.007, 0.222±0.003, 0.251±0.015, 0.483±0.029, 0.585±0.035, respectively, F= 215.3, P< 0.05; the expression of Beclin-1 was 0.059±0.002, 0.080±0.002, 0.087±0.002, 0.183±0.007, 0.228±0.005, respectively, F= 137.3, P< 0.05) in human nasal epithelial cells. TEM analysis showed typical autophagosome and autolysosome in cells after PM2.5 exposure for 24 h. PM2.5 significantly increased the number of yellow and red dots representing autophagosomes and autolysosomes respectively, indicating autophagic flux was elevated. Moreover, PM2.5 enhanced the secretion of inflammatory cytokines such as IL-6 and TNF-α, which was dramatically prevented by Atg5-siRNA and Beclin-1-siRNA. Conclusion: Autophagy plays an important role in PM2.5-caused inflammation response in nasal epithelial cells, which can induce release of inflammatory factors such as IL-6 and TNF-α and advance the inflammatory reaction.

Biochar, pyrolyzed from agricultural biomass wastes, has been widely used as an improver in wastewater treatment to regulate the oxygen distributions and microbial communities because of its extended surface area and porous structure. In addition, biochar has been shown to play a role in enhancing the porosity, adsorbing ammonium (NH 4 + -N), and reducing nitrous oxide (N 2 O) emissions. In this paper, five groups of constructed microcosm wetlands (CW) were built in a greenhouse with different biochar doses of 40%, 30%, 20%, 10%, and 0% (named as BW-40, BW-30, BW-20, BW-10, and CW-K, respectively) to investigate the influences of biochar on pollutant removal efficiencies and N 2 O emissions. The results showed that the concentration of effluent dissolved oxygen (DO) was less than 0.5 mg·L -1 , and the pH was stable at around 7.2 in every CW. Additionally, the effluent oxidation-reduction potential (ORP) was found to have moderately increased with the increases in the quantity of biochar, and the conductivity (Cond) test results showed the opposite trend. However, the effects of biochar on DO, pH, ORP, and Cond were not significant ( P >0.05). The chemical oxygen demand (COD) removal rates were up to 90% in all CWs. On the other hand, significantly higher removal efficiencies for NH 4 + -N and total nitrogen (TN) were found in CWs filled with biochar ( P <0.05). The average NH 4 + -N removal rates were (57.96±10.63)%, (51.12±11.74)%, (48.55±8.75)%, (43.95±9.74)%, and (34.76±14.16)% in BW-40, BW-30, BW-20, BW-10, and CW-K, respectively, while the total nitrogen (TN) average removal rates were (80.21±10.63)%, (78.48±5.73)%, (76.80±4.20)%, (75.88±5.85)%, and (70.92±5.68)%, respectively. Nitrate (NO 3 - -N) was not detected in the CWs for there were sufficient carbon sources and suitable denitrification environments. Moreover, the average fluxes of N 2 O ranged from 13.53 mg·(m 2 ·d) -1 to 45.30 mg·(m 2 ·d) -1 in the experimental systems. Compared with the control, the reduction rates of N 2 O in the BW-40, BW30, BW20, and BW10 were 70.13%, 68.26%, 50.83%, and 37.90%, respectively, and the ratios of N 2 O emissions to the removed nitrogen in CWs with biochar were significantly lower than those in the CW without biochar. Positive correlations were observed between the N 2 O fluxes and nitrite (NO 2 - -N) concentrations, and the lower N 2 O emissions could be attributed to the higher oxygen transfer and lower NO 2 - -N accumulation rates in response to the biochar addition. These results demonstrate that biochar could be used as an amendment to strengthen the nitrogen removal and reduce the N 2 O emissions in CWs.

Objective: To investigate the effect of PM2.5 exposure on nasal inflammatory cytokines and nasal mucosal pathology in a rat model of allergic rhinitis (AR). Methods: Twenty-four healthy female SD rats were randomly divided into 3 groups by random number table method, with 8 rats in each group: normal control group (NC group), ovalbumin (OVA) induced AR model (AR group), and AR model group inhaled to PM2.5 at 200 μg/m(3), 3 h/d, for 30 d (ARE group). Nasal symptoms including sneezing, nasal rubs and nasal secretion were recorded. Levels of OVA specific IgE in serum, interleukin 6 (IL-6) and tumor necrosis factor-ɑ (TNF-ɑ) in nasal irrigating solution were measured by enzyme-linked immunosorbent assay (ELISA). The histopathological changes of nasal mucosa were observed by HE staining. SPSS 17.0 software was used to analyze the data. Results: The number of sneezing, nasal rubs and the amount of nasal secretion in the ARE group were significantly higher than that in the AR group and the NC group (number of sneezing (15.38±1.68) times/15 min vs (11.63±1.13) times/15 min vs (1.75±0.71) times/15 min, number of nasal rubs (27.75±2.12) times/15 min vs (21.25±2.96) times/15 min vs (5.25±1.04) times/15 min, amount of nasal secretion (18.90±2.07) mg vs (13.83±1.81) mg vs (3.78±0.41) mg, F values was 236.089, 224.139, 183.971, respectively, all P< 0.001). Statistically significant differences in OVA specific IgE, IL-6 and TNF-ɑ levels were observed in ARE group exceeded AR group and NC group (OVA specific IgE (25.42±2.51) ng/ml vs (18.07±1.07) ng/ml vs (1.47±0.26) ng/ml, IL-6 (123.30±18.86) pg/ml vs (63.49±11.29) pg/ml vs (16.87±3.29) pg/ml, TNF-ɑ (162.50±38.15) pg/ml vs (72.96±11.28) pg/ml vs (27.52±4.15) pg/ml, F values was 481.604, 138.277, 63.938, respectively, all P< 0.001). HE staining showed that the nasal epithelial cells of NC group were intact and neatly arranged. Nasal mucosa epithelial cells were arranged in disorder in AR group, with tissue structure swelling. Partial shedding of nasal epithelial cells, mucosal basement membrane thickening, submucosal tissue interstitial edema, vasodilation and gland hyperplasia were found in ARE group. Conclusion: An increase inflammatory factors level such as IL-6 and TNF-ɑ aggravates pathological damage of nasal mucosa in a rat model of AR by exposure to PM2.5.

Objective: The aim of this study is to the roles of nasal lavage fluid levels of MUC5AC, goblet cell hyperplasia and ultrastructure of nasal mucosa following ambient PM2.5 exposure in a rat model of allergic rhinitis(AR). Method: Female Sprague-Dawley rats were assigned randomly into 3 groups: a negative control group(NC group),an ovalbumin(OVA)-induced AR model group(AR group), and AR model group(ARE group) inhaled to PM2.5 at 200 μg/m³, 3 h/d, for 30 days. Nasal symptoms, levels of MUC5AC in nasal lavage fluid(NLF), were measured in each individual rat.Goblet cell hyperplasia were examined histologically with PAS-stained. Nasal mucosa tissue ultrastructure were observed by scanning electron microscope. Result: PM2.5 significantly increased the number of sneezes, nasal rubs and the amount of nasal secretion in rats with AR.Statistically significant differences in MUC5AC levels and goblet cell hyperplasia were observed between the AR model exposure to PM2.5 and the AR model group.The nasal mucosa of AR model exposure to PM2.5 was disordered,lodged,assembled and twisted. Conclusion: Our data indicate that an increase MUC5AC level in NLF and the development of nasal goblet cell hyperplasia may provide some clues for determining the pathogenic mechanisms of AR by exposure to PM2.5., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Triboelectric nanogenerators (TENGs) have been invented recently for meeting the power requirements of small electronics and potentially solving the worldwide energy crisis. Here, we developed a vertical contact-separation mode TENG based on a novel multi-dielectric-layered (MDL) structure, which was comprised of parylene C, polyimide and SiO 2 films. By using the corona discharge approach, the surface charge density was enhanced to as high as 283 μC m -2 , and especially the open-circuit voltage could be increased by a factor of 55 compared with the original value. Furthermore, the theoretical models were built to reveal the output characteristics and store the electrostatic energy of the TENG. The influences of the structural parameters and operation conditions including the effective dielectric thickness, dielectric constant, gap distance and air breakdown voltage were investigated systematically. It was found that the output performances such as the peak voltage and power density are approximately proportional to the thickness of the MDL film, but they would be restricted by the air breakdown voltage. These unique structures and models could be used to deepen the understanding of the fundamental mechanism of TENGs, and serve as an important guide for designing high performance TENGs.

Background: Exposure to fine particulate matter (particulate matter ≤2.5 μm [PM2.5]) increases the risk of allergic rhinitis (AR), but the underlying mechanisms remains unclear. Thus, we investigated the roles of T-helper (Th)1-Th2 cytokines and nasal remodeling after ambient PM2.5 exposure in a rat model of AR., Methods: Female Sprague-Dawley rats were randomized into six groups: a negative control group, a group of healthy rats exposed to 3000 μg/m3 PM2.5, an ovalbumin (OVA) induced AR model, and three PM2.5-exacerbated AR groups exposed to three different concentrations (200, 1000, and 3000 μg/m3) of PM2.5 for 30 days via inhalation. Nasal symptoms, levels of Th1-Th2 cytokines, the degree of eosinophilia in nasal lavage fluid (NLF), and the messenger RNA (mRNA) expressions of transcription factors GATA-3 and T-bet in the nasal mucosa were measured in each individual rat. Hyperplasia of globet cells and collagen deposition were examined by histology., Results: PM2.5 significantly increased the number of sneezes and nasal rubs in rats with AR. PM2.5 also significantly decreased interferon gamma and increased interleukin (IL) 4 and IL-13 expressions as well as the number of eosinophils in NLF. The mRNA expression of GATA-3 in the nasal mucosa of rats with AR was upregulated by PM2.5, whereas T-bet was significantly downregulated. Statistically significant differences in OVA-specific serum immunoglobulin E, goblet cell hyperplasia, collagen deposition, and transforming growth factor beta 1 levels were observed between the PM2.5-exacerbated AR groups and the AR model group., Conclusion: Analysis of our data indicated that an increase in the immune response with Th2 polarization and the development of nasal remodeling may be the immunotoxic mechanisms behind the exacerbation of AR after exposure to PM2.5.

This study aimed to reveal the genetic and epigenetic variations involved in a resynthesized Brassica napus (AACC) generated from a hybridization between a B. rapa (AA) landrace and B. alboglabra (CC). Amplified fragment length polymorphism (AFLP), methylation-sensitive amplified polymorphism, and the cDNA-AFLP technique were performed to detect changes between different generations at the genome, methylation, and transcription levels. We obtained 30 lines of resynthesized B. napus with a mean 1000-seed weight of over 7.50 g. All of the lines were self-compatible, probably because both parents were self-compatible. At the genome level, the S0 generation had the lowest frequency of variations (0.18%) and the S3 generation had the highest (6.07%). The main variation pattern was the elimination of amplified restriction fragments on the CC genome from the S0 to the S4 generations. At the methylation level, we found three loci that exhibited altered methylation patterns on the parental A genome; the variance rate was 1.35%. At the transcription level, we detected 43.77% reverse mutations and 37.56% deletion mutations that mainly occurred on the A and C genomes, respectively, in the S3 generation. Our results highlight the genetic variations that occur during the diploidization of resynthesized B. napus.

Objective: This study examines the effect of Dextromethorphan (d-3-methoxy-17-methylmorphinan; DXM), a commonly used cough-suppressing drug, on the expression of VCAM-1 and ICAM-1 in human umbilical vein endothelial cells (HUVECs) stimulated with lipopolysaccharide (LPS)., Methods: The effect of DXM on expression of cell adhesion molecules induced by LPS was evaluated by monocyte bindings in vitro and ex vivo and transmigration assays. The signaling pathways involved in the inflammation inhibitory effect of DXM were analyzed by Western blot and immunofluorescent stain., Results: Pretreatment of HUVECs with DXM inhibited LPS-induced adhesion of THP-1 cells in vitro and ex vivo, and reduced transendothelial migration of these cells. Furthermore, treatment of HUVECs with DXM can significantly decrease LPS-induced expression of ICAM-1 and VCAM-1. DXM abrogated LPS-induced phosphorylation of ERK and Akt. The translocation of early growth response gene-1 (Egr-1), a downstream transcription factor involved in the mitogen-activated kinase (MEK)-ERK signaling pathway, was suppressed by DXM treatment. Furthermore, DXM inhibited LPS-induced IκBα degradation and nuclear translocation of p65., Conclusions: Dextromethorphan inhibits the adhesive capacity of HUVECs by reducing the LPS-induced ICAM-1 and VCAM-1 expression via the suppression of the ERK, Akt, and NF-κB signaling pathways. Thus, DXM is a potential anti-inflammatory therapeutic that may modulate atherogenesis., (© 2012 John Wiley & Sons Ltd.)

Background: We established the association between arsenic ingestion and increased risk of vascular diseases associated with diabetes. However, the specific microvascular diseases in relation to arsenic exposure level have not been well reported., Methods: The study population was obtained through national health database linkage. A total of 28 499 subjects living in the study area were successfully linked with their medical records from the National Health Insurance database in 1999-2000. The arsenic concentrations of artesian well water in the villages of the study area were utilized as indices of previous ingestion level. Both stratified analysis and unconditional logistic regression were used to examine mainly neurological and renal disease in relation to the arsenic exposure taking into account diabetes status., Results: The age-adjusted and gender-adjusted prevalence of microvascular diseases was 7.51% [95% confidence interval (CI) 7.50-7.51] for arsenic level of <0.1 mg/litre, and then increased from 6.59% (6.59-6.60) for the arsenic concentrations of 0.1-0.29 mg/litre to 8.02% (8.02-8.03) and 11.82% (11.81-11.83) for those of 0.3-0.59 mg/litre and > or =0.6 mg/litre in non-diabetic subjects. For diabetic patients, the prevalence was 16.41% (95% CI 16.37-16.45), 15.85% (15.8-15.9), 21.69% (21.6-21.8), and 28.31% (28.2-28.4) for arsenic levels <0.1, 0.1-0.29, 0.3-0.59, and > or =0.6 mg/litre, respectively. The prevalence of microvascular diseases increased significantly with arsenic exposure, especially at higher levels, and the relationship is stronger in diabetics than in non-diabetic subjects. The results for neurological disease are very similar, and the patterns are the same for renal disease., Conclusions: The increased prevalence of microvascular diseases, including neurological and renal disorders, is associated with arsenic ingestion. This excess risk was further elevated in diabetic subjects. Further studies are necessary to verify the hypotheses of threshold or dose-response relationships.