Association between ambient carbon monoxide levels and hospitalization costs of patients with myocardial infarction: Potential effect modification by ABO blood group.

Previous researches have reported the association between air pollution and various diseases. However, few researches have investigated whether air pollutants are associated with the economic loss resulting from patients' hospitalization, especially the economic loss of hospitalization due to acute cardiovascular events. The purpose of our research was to explore the association between the levels of carbon monoxide (CO), taken as an index of pollution, and the hospitalization costs of myocardial infarction (MI), and the potential effect modification by the ABO blood group. A total of 3237 MI inpatients were included in this study. A multiple linear regression model was used to evaluate the association between ambient CO levels and hospitalization costs of MI patients. Moreover, we performed stratified analyses by age, gender, body mass index (BMI), season, hypertension, and ABO blood types. There was a positive association between the levels of CO in the air and the costs of hospitalization caused by MI. Furthermore, such association was stronger in males, BMI ≥25, <65 years, with hypertension, and non-O blood group. Interestingly, we found the association was particularly significant in patients with blood group B. Overall, our study first found that ambient CO levels could have an impact on the hospitalization costs for MI patients, and those with blood group B can be more sensitive.

Dietary calcium intake and the risk of stroke: Meta-analysis of cohort studies.

BACKGROUND AND AIMS: Prospective cohorts are inconsistent regarding the association between dietary calcium intake and the risk of stroke. The aim was to perform a meta-analysis to determine whether an association exists between them in cohort studies. METHODS AND RESULTS: Relevant studies were identified by searching PubMed, EMBASE and Web of Science databases that published before December 2022. Prospective cohort studies that provided relative risk (RR) estimates with 95% confidence intervals (CIs) for the association were included. Study-specific risk estimates were combined by using a random effects model. Eighteen prospective studies, including 19,557 stroke cases among 882,181 participants, were pooled in the meta-analysis. We observed a nonlinear association between calcium intake and risk of stroke (Pnonlinearity < 0.003). Compared with the lowest value of zero assumed as the reference, the RRs (95% CI) of stroke across levels of calcium intake were 0.95 (0.92, 0.98) for 200 mg/day, 0.94 (0.90, 0.98) for 300 mg/day, 0.95 (0.90, 0.99) for 500 mg/day, 0.98 (0.93, 1.03) for 700 mg/day, and 1.04 (0.97, 1.11) for 1000 mg/day. The stratified analyses by geographic region showed nonlinear associations and indicated that the protective effect was observed in Asian countries (Pnonlinearity = 0.001) but not in non-Asian regions (Pnonlinearity = 0.047). CONCLUSION: This meta-analysis suggests that dietary calcium intake might play an effective role in the prevention of stroke, especially in Asian countries. Future research among Asia population should attempt to establish whether this association is causal. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022357710.

MNK2-eIF4E axis promotes cardiac repair in the infarcted mouse heart by activating cyclin D1.

Adult mammals have limited potential for cardiac regeneration after injury. In contrast, neonatal mouse heart, up to 7 days post birth, can completely regenerate after injury. Therefore, identifying the key factors promoting the proliferation of endogenous cardiomyocytes (CMs) is a critical step in the development of cardiac regeneration therapies. In our previous study, we predicted that mitogen-activated protein kinase (MAPK) interacting serine/threonine-protein kinase 2 (MNK2) has the potential of promoting regeneration by using phosphoproteomics and iGPS algorithm. Here, we aimed to clarify the role of MNK2 in cardiac regeneration and explore the underlying mechanism. In vitro, MNK2 overexpression promoted, and MNK2 knockdown suppressed cardiomyocyte proliferation. In vivo, inhibition of MNK2 in CMs impaired myocardial regeneration in neonatal mice. In adult myocardial infarcted mice, MNK2 overexpression in CMs in the infarct border zone activated cardiomyocyte proliferation and improved cardiac repair. In CMs, MNK2 binded to eIF4E and regulated its phosphorylation level. Knockdown of eukaryotic translation initiation factor (eIF4E) impaired the proliferation-promoting effect of MNK2 in CMs. MNK2-eIF4E axis stimulated CMs proliferation by activating cyclin D1. Our study demonstrated that MNK2 kinase played a critical role in cardiac regeneration. Over-expression of MNK2 promoted cardiomyocyte proliferation in vitro and in vivo, at least partly, by activating the eIF4E-cyclin D1 axis. This investigation identified a novel target for heart regenerative therapy.

The association between short-term exposure to ambient carbon monoxide and hospitalization costs for bronchitis patients: A hospital-based study.

Ambient carbon monoxide (CO) is associated with bronchitis morbidity, but there is no evidence concerning its correlation with hospitalization costs for bronchitis patients. This study aimed to investigate the relationship between short-term ambient CO exposure and hospitalization costs for bronchitis patients in Chongqing, China. Baseline data for 3162 hospitalized bronchitis patients from November 2013 to December 2019 were collected. Multiple linear regression analysis was used to determine the association, delayed and cumulative, between short-term CO exposure and hospitalization costs. Additionally, subgroup analyses were performed by gender, age, season, and comorbidity. Positive association between CO and hospitalization costs for bronchitis patients was observed. The strongest association was observed at lag 015 days, with per 1 mg/m3 increase of CO concentrations corresponded to 5834.40 Chinese Yuan (CNY) (95% CI: 2318.71, 9350.08; P < 0.001) (845.97 US dollars) increment in hospitalization costs. Stratified analysis results showed that the association was more obvious among those males, elderly, with comorbidities, and in warm seasons. More importantly, there was strongest correlation between CO and bronchitis patients with coronary heart disease. In summary, short-term exposure to ambient CO, even lower than Chinese and WHO standards, can be associated with increased hospitalization costs for bronchitis. Controlling CO exposure can be helpful to reduce medical burden associated with bronchitis patients. The results also suggest that when setting air quality standards and formulating preventive measures, susceptible subpopulations ought to be considered.

Association between short-term ambient nitrogen dioxide and type 2 diabetes outpatient visits: A large hospital-based study.

Type 2 diabetes (T2DM) as a non-communicable disease imposes heavy disease burdens on society. Limited studies have been conducted to assess the effects of short-term air pollution exposure on T2DM, especially in Asian regions. Our research aimed to determine the association between short-term exposure to ambient nitrogen dioxide (NO2) and outpatient visits for T2DM in Chongqing, the largest city in western China, based on the data collected from November 28, 2013 to December 31, 2019. A generalized additive model (GAM) was applied, and stratified analyses were performed to investigate the potential modifying effects by age, gender, and season. Meanwhile, the disease burden was revealed from attributable risk. Positive associations between short-term NO2 and daily T2DM outpatient visits were observed. The strongest association was observed at lag 04, with per 10 µg/m3 increase of NO2 corresponded to increased T2DM outpatient visits at 1.57% [95% confidence interval (CI): 0.48%, 2.65%]. Stronger associations were presented in middle-aged group (35-64 years old), male group, and cool seasons (October to March). Moreover, there were 1.553% (8664.535 cases) of T2DM outpatient visits attributable to NO2. Middle-aged adults, males, and patients who visited in cool seasons suffered heavier burdens. Conclusively, short-term exposure to NO2 was associated with increased outpatient visits for T2DM. Attention should be paid to the impact of NO2 on the burden of T2DM, especially for those vulnerable groups.

Phase-Controlled Synthesis of Pd-Se Nanocrystals for Phase-Dependent Oxygen Reduction Catalysis.

Searching for highly efficient oxygen reduction reaction (ORR) electrocatalysts for fuel cell technology, in which the crystal structure plays a powerful role in regulating the electrocatalysis, is urgent yet challenging. Herein, we have explored the active and stable Pd-Se alloy electrocatalysts with controlled phase toward alkaline ORR. The phase-controlled Pd-Se nanoparticles (NPs) show interesting phase-dependent electrocatalytic performance, in which the Pd17Se15 NPs/C exhibits much better ORR performance than its counterpart, Pd7Se4 NPs/C, and the commercial Pd/C and Pt/C. Based on the detailed analysis, Pd in Pd17Se15 possesses more Se atom coordination and a higher valence state, thus providing a stronger capacity for the absorption of oxygenated species. DFT further reveals more charge transfer from the Pd17Se15 surface to the *OOH intermediate, which is the reason for the activity enhancement.

Sn(101) Derived from Metal-Organic Frameworks for Efficient Electrocatalytic Reduction of CO2.

The synthesis of a specific Sn plane as an efficient electrocatalyst for CO2 electrochemical reduction to generate fuels and chemicals is still a huge challenge. Density functional theory (DFT) calculations first reveal that the Sn(101) crystal plane is more advantageous for CO2 electroreduction. A metal-organic framework (MOF) precursor Sn-MOF has been carbonized and then etched to successfully fabricate Sn(101)/SnO2/C composites with good control of the carbonization time and the concentration of hydrochloric acid. The Sn(101) crystal plane of the catalyst could enhance the faradaic efficiency of formate to as high as 93.3% and catalytic stability up to 20 h. The promotion of the selectivity and activity by Sn(101) advances new possibilities for the rational design of high-activity Sn catalysts derived from MOFs.

Association between short-term ambient air pollution and outpatient visits of anxiety: A hospital-based study in northwestern China.

Anxiety, a common and devastating mental disorder, has raised widespread interests. The impacts of air pollution on physical health are well known, whereas few studies have explored the association of atmospheric pollution, especially short-term air pollution exposure, with the risk of anxiety disorders. In addition, there are increasing concerns in emerging evidence supporting a possible etiological link. Therefore, our aim was to evaluate the relationship between short-term exposure to atmospheric pollutants and anxiety outpatient visits in Xi'an, a city of northwestern China and a metropolis with relatively heavy air pollution. We collected the data of both daily outpatient visits and daily air pollution (SO2, NO2, and PM10) between January 1, 2010 and January 31, 2016 (2222 days). To clarify the association between short-term ambient atmospheric pollution exposure and anxiety outpatient visits, an over-dispersed Poisson generalized additive model was applied by adjusting the day of the week and weather conditions (including temperature, humidity, sunlight hours, and rainfalls). Positive association between gaseous air pollutants (SO2 and NO2) and anxiety daily outpatient visits was observed. Moreover, the largest estimated values of both SO2 and NO2 were evidence at lag 03 (4-day moving average lag), with 10 µg/m3 increase corresponded to the increase of outpatient anxiety visits at 4.11% (95% CI: 2.15%, 6.06%) for SO2 and 3.97% (95% CI: 1.90%, 6.06%) for NO2. However, there was no differences in susceptibility to air pollutants between different genders as well as different ages. Taken together, short-term exposure to ambient air pollutants, especially gaseous air pollutants (NO2 and SO2), can be related to higher risk of anxiety outpatient visits.

Association between short-term ambient air pollution exposure and depression outpatient visits in cold seasons: a time-series analysis in northwestern China.

Depression is known to be one of the most common mental disorders raising global concerns. However, evidence regarding the association between short-term air pollution exposure and risk of development of depression is limited. The aim of this was to assess the relationship between short-term ambient air pollution exposure and depression in outpatient visits in Xi'an, a northwestern Chinese metropolis. Data for air pollutants including particulate matter (PM10), sulfur dioxide (SO2), and nitrogen dioxide (NO2) levels from October 1, 2010 to December 31, 2013 and number of daily depression outpatient visits (92,387 in total) were collected. A time-series quasi-Poisson regression model was adopted to determine the association between short-term air pollutant concentrations and frequency of outpatient visits for depression with different lag models. Consequently, 10 µg/m3 increase of SO2 and NO2 levels corresponded to significant elevation in number of outpatient-visits for depression on concurrent days (lag 0), and this relationship appeared stronger in cool seasons (October to March). However, the association of PM10 was only significant in males aged 30-50 at lag 0. Evidence indicated that short-term exposure to ambient air pollutants especially in cool seasons might be associated with increased risk of outpatient visits for depression.

Short-term ambient nitrogen dioxide exposure is associated with increased risk of spontaneous abortion: A hospital-based study.

There are increasing concerns with regard to spontaneous abortion (SAB), the loss of pregnancy without external intervention before 20 weeks of gestation, among reproductive-aged women. To date, limited evidence is available concerning the association between SAB and air pollutants, especially in developing countries. Daily baseline outpatient data for SAB from January 1, 2014, to December 31, 2018 (1826 days) were obtained in Chongqing, a metropolis of southwest China. The over-dispersed Poisson generalized additive model with control of meteorological conditions and day of week was used to estimate the short-term effects of ambient air pollution on the daily number of SAB outpatients. A total of 42,334 SAB outpatient visits for SAB were recorded. No statistically significant association was observed between SAB and CO, PM2.5, PM10, O3, and SO2. The positive association only appeared for NO2: positive associations between SAB and NO2 were observed in both single-day models (lag 0, lag 1, lag 3, and lag 4) and cumulative exposure models (lag 01, lag 03, and lag 05) and the most significant effects were observed at lag 05 (3.289%; 95% CI: 1.568%, 5.011%). Moreover, the women with higher ages (30-39 and > 39) were more sensitive than those with lower ages (18-29), and the effect estimates were more evident in cool seasons. Collectively, our results suggested that short-term NO2 exposure was associated with higher risk of SAB, especially in elder women and cool seasons, which may contribute to further understand the role of air pollution on SAB and other adverse obstetric outcomes.

Association between air pollution and menstrual disorder outpatient visits: A time-series analysis.

Menstrual disorders are common diseases among reproductive-aged women with increasing concerns. Until now, there have been limited studies about the association between menstrual disorders and air pollution. This study aimed to investigate the association between short-term (concurrent day and within 1 week prior) ambient air pollution exposure and menstrual disorder outpatient visits in Xi'an, a metropolis in northwestern China. Daily baseline outpatient data of menstrual disorders from January 1, 2010 to February 18, 2016 (2239 days) were obtained. An over-dispersed Poisson generalized additive model was applied to discover the relationship between short-term air pollution exposure and the number of menstrual disorder outpatient visits by adjusting the day of the week and weather conditions. A total of 51,893 outpatient visits for menstrual disorders were recorded. A 10 µg/m3 increase of PM10 and NO2 concentrations corresponded to 0.236% (95% Cl: 0.075%, 0.397%) and 2.173% (95% Cl: 0.990%, 3.357%) elevations in outpatient-visits for menstrual disorders at lag 7 and lag 01 (concurrent day and previous 1 day), respectively. The association was more significant in young females (18-29 years) and there was no obvious association observed between SO2 and menstrual disorder outpatient visits. This is the first evidence that short-term exposure to ambient air pollution can be associated with an increased risk of menstrual disorder attacks. The results of our study may help to establish more comprehensive understanding of the health effects of ambient air pollution on menstrual disorders and other reproductive diseases.

A novel long noncoding RNA FAF inhibits apoptosis via upregulating FGF9 through PI3K/AKT signaling pathway in ischemia-hypoxia cardiomyocytes.

Long noncoding RNAs (lncRNAs) have been increasingly considered to play an important role in the pathological process of various cardiovascular diseases, which often bind to the proximal promoters of the protein-coding gene to regulate the protein expression. However, the functions and mechanisms of lncRNAs in cardiomyocytes have not been fully elucidated. High-throughput RNA sequencing was performed to identify the differently expressed lncRNAs and messenger RNAs (mRNAs) between acute myocardial infarction (AMI) rats and healthy controls. One novel lncRNA FGF9-associated factor (termed FAF) and mRNAs in AMI rats were verified by bioinformatics, real-time polymerase chain reaction or western blot. Moreover, RNA fluorescence in situ hybridization was performed to determine the location of lncRNA. Subsequently, a series of in vitro assays were used to observe the functions of lncRNA FAF in cardiomyocytes. The expression of lncRNA FAF and FGF9 were remarkably decreased in ischemia-hypoxia cardiomyocytes and heart tissues of AMI rats. Overexpression of FAF could significantly inhibit cardiomyocytes apoptosis induced by ischemia and hypoxia. Conversely, knockdown of lncRNA FAF could promote apoptosis in ischemia-hypoxia cardiomyocytes. Moreover, overexpression of lncRNA FAF could also increase the expression of FGF9. Knockdown of the FGF9 expression could promote apoptosis in cardiomyocytes with the insult of ischemia and hypoxia, which was consistent with the effect of lncRNA FAF overexpression on cardiomyocyte apoptosis. Mechanistically, FGF9 inhibited cardiomyocytes apoptosis through activating signaling tyrosine kinase FGFR2 via phosphoinositide 3-kinase/protein kinase B signaling pathway. Thus, lncRNA FAF plays a protective role in ischemia-hypoxia cardiomyocytes and may serve as a treatment target for AMI.

A pilot clinical study of adjunctive therapy with selective intracoronary hypothermia in patients with ST-segment elevation myocardial infarction.

OBJECTIVES: We aimed to assess the effect of selective intracoronary hypothermia on outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). BACKGROUND: Intracoronary hypothermia, the feasibility and safety of which has been validated in humans, induced by selective trans-coronary infusion of saline at different temperatures can reduce infarct size (IS) prior to reperfusion in animal models of STEMI. METHODS: Sixty STEMI patients presenting with thrombolysis in myocardial infarction (TIMI) flow grade 0/1 were randomized after coronary artery angiography. Intracoronary hypothermia was induced by selective trans-coronary infusion of saline at 4°C to the endangered myocardium in the 30 patients. The primary endpoint, absolute IS expressed as IS/myocardium at risk (MaR), was assessed by cardiac magnetic resonance imaging at day 7 post-PPCI in 50 patients. Clinical follow-up was undertaken at day 30 after procedure. RESULTS: Intracoronary hypothermia was successfully performed in hypothermia group, without increase in arrhythmia or hemodynamic instability. The mean temperature reduction of 5.8 ± 1.1°C in distal coronary artery was achieved before reperfusion. Mean IS/MaR was predominantly reduced in the hypothermia group (44.85 ± 5.89% vs. 50.69 ± 10.75%, P = 0.022), especially in the anterior STEMI subgroup (46.12 ± 7.54% vs. 55.27 ± 11.175%, P = 0.023). The clinical events appeared no statistical difference between the two groups at the 30-day follow-up. CONCLUSION: The statistical difference in IS/MaR by intracoronary hypothermia as adjunctive therapy to PPCI is an important observation and warrants a larger pivotal trial fully powered for efficacy.

Tuning the activity of the inert MoS2 surface via graphene oxide support doping towards chemical functionalization and hydrogen evolution: a density functional study.

The basal plane of MoS2 provides a promising platform for chemical functionalization and the hydrogen evolution reaction (HER); however, its practical utilization remains challenging due to the lack of active sites and its low conductivity. Herein, using first principles simulations, we first proposed a novel and effective strategy for significantly enhancing the activity of the inert MoS2 surface using a graphene oxide (GO) support (MoS2/GOs). The chemical bonding of the functional groups (CH3 and NH2) on the MoS2-GO hybrid is stronger than that in freestanding MoS2 or MoS2-graphene. Upon increasing the oxygen group concentration or introducing N heteroatoms into the GO support, the stability of the chemically functionalized MoS2 is improved. Furthermore, use of GOs to support pristine and defective MoS2 with a S vacancy (S-MoS2) can greatly promote the HER activity of the basal plane. The catalytic activity of S-MoS2 is further enhanced by doping N into GOs; this results in a hydrogen adsorption free energy of almost zero (ΔGH = ∼-0.014 eV). The coupling interaction with the GO substrate reduces the p-type Schottky barrier heights (SBH) of S-MoS2 and modifies its electronic properties, which facilitate charge transfer between them. Our calculated results are consistent with the experimental observations. Thus, the present results open new avenues for the chemical functionalization of MoS2-based nanosheets and HER catalysts.

Short-term air pollution exposure is associated with hospital length of stay and hospitalization costs among inpatients with type 2 diabetes: a hospital-based study.

Air pollution is a risk factor for type 2 diabetes (T2D), exerting heavy economic burden on both individuals and societies. However, there is no apparent report regarding the influence of air pollutants such as particulate matter (PM2.5 and PM10), sulfur dioxide (SO2), carbon monoxide (CO), nitrogen dioxide (NO2), and ozone (O3) on financial burden to individuals and societies suffering from T2D. This study aimed to determine whether short-term (no more than 16 d) air pollution exposure was associated with T2D-related length of stay (LOS) and hospitalization expenses incurred by patients. This investigation examined 2840 T2D patients hospitalized from December 17, 2013 to May 31, 2016 in China. Multiple linear regression analysis was applied to determine the association between short-term (no more than 16 d) ambient air pollution, LOS, and hospitalization expenses, controlling for age, gender, ethnicity, marital status, and weather conditions. Sulfur dioxide (SO2) and carbon monoxide (CO) were significantly positively while nitrogen dioxide (NO2) was negatively associated with presence of T2D, LOS, and expenses. A 10-µg/m3 rise in 16-d (lag 0-15) average concentrations of SO2 and CO prior to hospitalization was correlated with a significant elevation in LOS and elevation in expenses in T2D patients. However, a 10-µg/m3 rise in 16-d average NO2 was associated with marked negative alterations in LOS and hospital costs in T2D patients. Taken together, data demonstrate that exposure to air pollutants impacts differently on LOS and hospitalization costs for T2D patients. This is the first apparent report regarding the correlation between air pollution exposure and clinical costs of T2D in China. It is of interest that air pollutants affected T2D patients differently as evidenced by LOS and clinical expenses where SO2 and CO exhibited a positive adverse relationship in contrast to NO2.

[Protective effect of astrocyte exosomes on hypoxic-ischemic neurons].

OBJECTIVE: To study the effect of astrocyte exosomes on hypoxic-ischemic neurons. METHODS: Rat astrocytes were cultured in vitro, and differential centrifugation was used to obtain the exosomes from the cell supernatant. Transmission electron microscopy, Nanosight, and Western blot were used for the identification of exosomes. BCA method was used to measure the concentration of exosomes. Rat neurons were cultured in vitro and then divided into control group, exosome group, oxygen glucose deprivation (OGD) group, and OGD+exosome group (n=3 each). The OGD and OGD+exosome groups were cultured in glucose-free medium under the hypoxic condition. The exosome and OGD+exosome groups were treated with exosomes at a final concentration of 22 μg/mL. The control and OGD groups were given an equal volume of phosphate-buffered saline. ELISA was used to measure the level of lactate dehydrogenase (LDH) in neurons. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to measure the apoptotic index of neurons. RESULTS: The identification of exosomes showed that the exosomes extracted by differential centrifugation had the features of exosomes. Compared with the control and exosome groups, the OGD group had significant increases in LDH level and apoptotic index (P<0.05). Compared with the OGD group, the OGD+exosome group had significant reductions in LDH level and apoptotic index (P<0.05). CONCLUSIONS: The exosomes from astrocytes have a protective effect on neurons with hypoxic-ischemic injury.

Epigallocatechin-3-Gallate Inhibits Matrix Metalloproteinase-9 and Monocyte Chemotactic Protein-1 Expression Through the 67-κDa Laminin Receptor and the TLR4/MAPK/NF-κB Signalling Pathway in Lipopolysaccharide-Induced Macrophages.

BACKGROUND/AIMS: Epigallocatechin-3-gallate (EGCG), a major catechin found in green tea, has been shown to prevent cardiovascular diseases. Previously, Matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1) and toll-like receptor 4 (TLR4) were confirmed to play an important role in atherosclerosis and plaque instability. Both TLR4 and its negative regulator, Toll-interacting protein (Tollip), could be mediated by EGCG. The present study aimed to examine the effect of physiological concentration of EGCG (1 µM) on the expression of MMP-9 and MCP-1 in lipopolysaccharide (LPS)-induced macrophages and the potential mechanisms underlying its actions. METHODS: The RAW264.7 cell line was used. Western blot was used to determine MCP-1, TLR4, Tollip, Mitogen-activated protein kinase (MAPK) and Nuclear factor-κB (NF-κB) protein expression. MMP-9 activity was assayed by gelatine zymography. The mRNA expression of MMP-9 and MCP-1 was measured by realtime polymerase chain reaction (RT-PCR). RESULTS: EGCG (1 µM) significantly suppressed the expression of MMP-9 and MCP-1 and inhibited MAPK and NF-κB in LPS-induced macrophages but was blocked by Tollip silencing. The expression of LPS-induced MMP-9 and MCP-1 and the phosphorylation of the ERK1/2, P38 and NF-κB pathway proteins decreased after TLR4 siRNA treatment. Furthermore, EGCG mediated TLR4 and Tollip expression through binding to 67-kDa laminin receptor (67LR). CONCLUSION: The results of our study suggested that EGCG (1 µM) suppresses the TLR4/MAPK/NF-κB signalling pathway, decreases the expression of the plaque instability-mediating cytokines MMP-9 and MCP-1, and might prove to be effective in stabilizing atherosclerotic plaque.

[Protective effect of histone acetylation against cortical injury in neonatal rats].

OBJECTIVE: To investigate the protective effect of histone acetylation against hypoxic-ischemic cortical injury in neonatal rats. METHODS: A total of 90 neonatal rats aged 3 days were divided into three groups: sham-operation, cortical injury model, and sodium butyrate (a histone deacetylase inhibitor) treatment. The rats in the model and the sodium butyrate treatment groups were intraperitoneally injected with lipopolysaccharide (0.05 mg/kg), and then right common carotid artery ligation was performed 2 hours later and the rats were put in a hypoxic chamber (oxygen concentration 6.5%) for 90 minutes. The rats in the sham-operation group were intraperitoneally injected with normal saline and the right common carotid artery was only separated and exposed without ligation or hypoxic treatment. The rats in the sodium butyrate treatment group were intraperitoneally injected with sodium butyrate (300 mg/kg) immediately after establishment of the cortical injury model once a day for 7 days. Those in the sham-operation and the model groups were injected with the same volume of normal saline. At 7 days after establishment of the model, Western blot was used to measure the protein expression of histone H3 (HH3), acetylated histone H3 (AH3), B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2-associated X protein (BAX), cleaved caspase-3 (CC3), and brain-derived neurotrophic factor (BDNF). Immunofluorescence assay was used to measure the expression of 5-bromo-2'-deoxyuridine (BrdU) as the cortex cell proliferation index. RESULTS: The sodium butyrate treatment group had a significantly lower HH3/AH3 ratio than the model group (P<0.05), which suggested that the sodium butyrate treatment group had increased acetylation of HH3. Compared with the model group, the sodium butyrate treatment group had a significant increase in Bcl-2/Bax ratio, a significant reduction in CC3 expression, and a significant increase in BDNF expression (P<0.05). The sodium butyrate treatment group had a significant increase in the number of BrdU-positive cells in the cortex compared with the model group (P<0.05), and BrdU was mainly expressed in the neurons. CONCLUSIONS: Increased histone acetylation may protect neonatal rats against cortical injury by reducing apoptosis and promoting regeneration of neurons. The mechanism may be associated with increased expression of BDNF.

Inhibition of EMMPRIN and MMP-9 Expression by Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor in PMA-Induced Macrophages.

BACKGROUND/AIMS: It is well documented that overexpression of EMMPRIN (extracellular matrix metalloproteinase inducer) and MMPs (matrix metalloproteinases) by monocytes/macrophages plays an important role in atherosclerotic plaque rupture. Green tea polyphenol epigallocatechin-3-gallate (EGCG) has a variety of pharmacological properties and exerts cardiovascular protective effects. Recently, the 67-kD laminin receptor (67LR) has been identified as a cell surface receptor of EGCG. The aim of the present study was to evaluate the effects of EGCG on the expression of EMMPRIN and MMP-9 in PMA-induced macrophages, and the potential mechanisms underlying its effects. METHODS: Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA). Protein expression and MMP-9 activity were assayed by Western blot and Gelatin zymography, respectively. Real-time PCR was used to examine EMMPRIN and MMP-9 mRNA expression. RESULTS: We showed that EGCG (10-50µmol/L) significantly inhibited the expression of EMMPRIN and MMP-9 and activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) in PMA-induced macrophages. Downregulation of EMMPRIN by gene silencing hindered PMA-induced MMP-9 secretion and expression, indicating an important role of EMMPRIN in the inhibition of MMP-9 by EGCG. Moreover, 67LR was involved in EGCG-mediated suppression of EMMPRIN and MMP-9 expression. Anti-67LR antibody treatment led to abrogation of the inhibitory action of EGCG on the expression of EMMPRIN and MMP-9 and activation of ERK1/2, p38, and JNK. CONCLUSION: Our results indicate that EGCG restrains EMMPRIN and MMP-9 expression via 67LR in PMA-induced macrophages, which also suggests that EGCG may be a possible therapeutic agent for stabilizing atherosclerotic plaque.

Acute effects of air pollution on enteritis admissions in Xi'an, China.

The correlation between enteritis, a common digestive disease, and exposure to ambient air pollutants has not been examined in a comprehensive manner. The aim of this study was to determine whether an association between short-term air pollution exposure and outpatient visits for enteritis in Xi'an, China, occurred using a time-series investigation. Daily baseline data from January 1, 2013, to December 31, 2015, were obtained. The overdispersed Poisson generalized additive model was used to analyze the association between air pollutant levels and frequency of enteritis. A total of 12,815 outpatient hospital visits for enteritis were identified. A 10-µg/m3 increase in average concentrations of particulate matter (PM)10, PM2.5, nitrogen dioxide (NO2), and sulfur dioxide (SO2), and a 0.1-mg/m3 rise of carbon monoxide (CO) were associated with a significantly elevated number of outpatient visits for enteritis on concurrent days, while ozone (O3) did not markedly affect the frequency of enteritis clinical visits. There were no significant positive effects between two-pollutant and single-pollutant models. Lag models showed that the most prominent responses occurred on concurrent days. Confounding factors of gender and age played a significant role in the observations. Taken together, data indicate that air pollution may result in enhanced occurrence of enteritis attack.