Mussel-Mimetic Hydrogel Coating with Anticoagulant and Antiinflammatory Properties on a Poly(lactic acid) Vascular Stent.

Biodegradable stents are the most promising alternatives for the treatment of cardiovascular disease nowadays, and the strategy of preparing functional coatings on the surface is highly anticipated for addressing adverse effects such as in-stent restenosis and stent thrombosis. Yet, inadequate mechanical stability and biomultifunctionality limit their clinical application. In this study, we developed a multicross-linking hydrogel on the polylactic acid substrates by dip coating that boasts impressive antithrombotic ability, antibacterial capability, mechanical stability, and self-healing ability. Gelatin methacryloyl, carboxymethyl chitosan, and oxidized sodium alginate construct a double-cross-linking hydrogel through the dynamic Schiff base chemical and in situ blue initiation reaction. Inspired by the adhesion mechanism employed by mussels, a triple-cross-linked hydrogel is formed with the addition of tannic acid to increase the adhesion and antibiofouling properties. The strength and hydrophilicity of hydrogel coating are regulated by changing the composition ratio and cross-linking degree. It has been demonstrated in tests in vitro that the hydrogel coating significantly reduces the adhesion of proteins, MC3T3-E1 cells, platelets, and bacteria by 85% and minimizes the formation of blood clots. The hydrogel coating also exhibits excellent antimicrobial in vitro and antiinflammatory properties in vivo, indicating its potential value in vascular intervention and other biomedical fields.

Smooth Muscle Overexpression of PGC1α Attenuates Atherosclerosis in Rabbits.

[Figure: see text].

Relationship between dry skin and pressure injury in older patients: A multicentre cross-sectional survey in China.

Dry skin and pressure injuries in older persons have become global health care problems. This was a multicentre, prospective cross-sectional study in 44 hospitals and 8 long term care institutions from 20 provinces, autonomous regions and municipalities in China and aimed to explore the relationship between the two skin problems in older patients. We mainly found 11 602 cases with dry skin and 1076 cases with pressure injuries in a total of 33 769 valid participants. The overall prevalence of dry skin and pressure injuries was 34.4% (95% confidence interval [CI] 33.9-34.9) and 3.1% (95% CI 2.9-3.3). Stage 2+ pressure injuries were the most (32.9%), followed by stage 1 (32.4%). The patients with dry skin had more pressure injuries than ones without dry skin (50.0% vs 33.9%). The patients with very severe and severe dry skin had more pressure injury risk (OR 2.22 and 1.90) and more stage 2+ pressure injury risk (OR 2.83 and 1.63). Other nine predictors associated with overall pressure injuries and stage 2+ pressure injuries. The area under receiver operating characteristic (ROC) curve of the predictive models of overall pressure injuries and stage 2+ pressure injuries were 0.89 (95% CI 0.88-0.90) and 0.91 (95% CI 0.90-0.92), respectively.

Nanozyme enhanced magnetic immunoassay for dual-mode detection of gastrin-17.

In this study, we developed a novel magnetic lateral flow assay based on iron oxide decorated with platinum probes (Fe3O4@Pt) for dual-mode detection of gastrin-17 (G-17), which is one of the main biomarkers for early gastric cancer diagnosis. The probe material exhibits both magnetic properties and peroxidase activity. The peroxidase activity enhances the intensity of the brownish coloring of the Fe3O4@Pt probes on the test strip, with a limit of detection of 10 pg mL-1 using the naked eye, which is remarkable for colorimetric lateral flow assays. The magnetic property allows the simple separation and enrichment of the sample, and the signal can be read using a magnetic assay reader for quantitative detection. The linear range for G-17 using the magnetic signal was determined as 10 pg mL-1 to 2200 pg mL-1, and the calculated limit of detection was as low as 3.365 pg mL-1, thereby covering the reference range for G-17. Serum samples were used to validate the test strip, which exhibited high sensitivity, high specificity, and consistency with the results obtained by the enzyme-linked immunosorbent assay method. The entire inspection process using this method can produce results within 35 min and it is simple to operate without requiring strict experimental conditions. This dual-mode lateral flow test strip provides a simple, rapid, and quantitative strategy for detecting G-17, and it may also be valuable in other portable diagnostic applications.

Association of functional variant of aldehyde dehydrogenase 2 with acute myocardial infarction of Chinese patients.

BACKGROUND: The variant of ALDH2 was thought to be associated with Acute Myocardial Infarction (AMI) due to the consumption of alcohol. This study focused on how ALDH2 variant acts as an independent risk factor for AMI, regardless of alcohol consumption. METHODS AND RESULTS: We used the case-control INTERHEART-China study which took place at 25 centres in 17 cities in mainland China. Cases were patients with AMI and matched by age, sex, and site to controls. Information about alcohol consumption and genotype were collected. We divided cases and controls by alcohol consumption: alcohol intake group and no alcohol intake group. Then, calculated the Odd Ratio (OR) value with confidence interval (CI) at 95% level to find the association between ALDH2 variant and AMI. Results were then adjusted by sex, age, BMI, and other common risk factors of AMI. The study involves a total of 2660 controls and 2322 AMI patients. The no drink intake group showed that there was a correlation between the ALDH2 variant and AMI (OR = 1.236, 95% CI = 1.090-1.401, p = 0.00092). After adjustment of different risk factors this association remained (OR = 1.247, 95% CI = 1.099-1.415, p = 0.00062). Similar results were also obtained from the no alcohol intake group (OR = 1.196, 95% CI = 0.993-1.440, p = 0.05963), however, due to the limited sample size, the result was not significant enough statistically. CONCLUSION: From our results, ALDH2 variant is associated with the risk of AMI even in population that has no alcohol consumption. This suggests that ALDH2 variant may act as an independent risk factor for AMI.

Association Between Skin Injuries in Medical Staff and Protective Masks Combined with Goggles During the COVID-19 Pandemic.

OBJECTIVE: To explore the relationship between wearing protective masks and goggles and skin injuries in medical staff during the COVID-19 pandemic. METHODS: Researchers conducted a cross-sectional, multicenter online survey. Respondents voluntarily completed the questionnaire on their smartphones. Ordinal and multinomial logistic regressions were used to identify factors related to skin injuries. RESULTS: In total, 1,611 respondents wore protective masks combined with goggles in 145 hospitals in China; 1,281 skin injuries were reported (overall prevalence, 79.5%). Multiple concomitant skin injuries (68.5%) and injuries in four anatomic locations (24.0%) were the most common, followed by injuries in three (22.8%), two (21.7%), and one location (11.0%). Multinomial logistic regression indicated that sweating increased the risk of injuries in one to four anatomic locations (95% confidence interval for odds ratio 16.23-60.02 for one location and 38.22-239.04 for four locations), and wearing an N95 mask combined with goggles and a daily use longer than 4 hours increased the risk of injuries in four locations (95% confidence interval for odds ratio 1.18-5.31 and 1.14-3.93, respectively). CONCLUSIONS: The prevalence of skin injuries among medical staff wearing protective masks combined with goggles was very high. These were mainly device-related pressure injuries, moisture-associated skin damage, and skin tears. The combination of various factors resulted in skin injuries at multiple sites. Preventing and managing sweating should be a focus for medical staff who wear protective masks combined with goggles for more than 4 hours.

The prevalence and prevention of pressure ulcers: A multicenter study of nine nursing homes in eastern China.

AIM: To assess the prevalence, related factors, and strategies for the prevention and treatment of pressure ulcers (PUs) in nursing homes in eastern China. MATERIALS AND METHODS: In this cross-sectional multicenter survey, assessments of 1158 residents in nine nursing homes in eastern China were conducted on a single day in August of 2019. RESULTS: Of the 1158 residents, 56 (4.8%) had at least one PU. Most of the identified PUs were classified as stage 3 (39.3%) and developed at home (55.4%). By multiple regression analysis, eating mode, bed-bound, and Braden score were significant association with the development of PUs in nursing homes. CONCLUSIONS: The prevalence of PUs in this study was similar to that reported by previous international studies. The implementation of measures for the prevention and treatment of PUs is insufficient in nursing homes in eastern China. Further, this study raised the issue of the lack of measures to prevent the development of PUs at home.

Conservative Management of Catastrophic Antiphospholipid Syndrome-Related Skin Necrosis: A Case Report.

Catastrophic antiphospholipid syndrome is an extremely rare autoimmune disease with complex and diverse clinical manifestations. Cutaneous necrosis is one of its rare clinical features. However, interventions for this manifestation are not standardized and lack evidence, which increases treatment difficulty. Here, study authors report the successful care and follow-up of a 46-year-old female patient with nephrotic syndrome and catastrophic antiphospholipid syndrome complicated by full-thickness cutaneous necrosis of the dorsum of the right hand that lasted more than 4 months and 1 month prior to wound treatment, respectively. Study authors set up an interprofessional team, including a nephrologist, a vascular surgeon, and two specialist wound care nurses to provide holistic wound care and treat her complex systemic conditions. After 84 days of treatment, which involved removing necrotic tissue with autolytic wound debridement, reducing inflammation with hydrofiber dressings containing silver, and promoting re-epithelialization with hydrocolloid paste and systemic medications, the wound healed successfully. Authors followed up with the patient at 1, 4, 6, 11, and 19 months after healing. The quality of scar was monitored, and the function of her right hand recovered normally.

A Multicenter, Comparative Study of Two Pressure-Redistribution Mattresses with Repositioning Intervals for Critical Care Patients.

OBJECTIVE: To compare the effectiveness of two protocols for preventing pressure injuries (PIs) in Chinese hospitals. DESIGN AND SETTING: A multicenter, open-label, comparative study conducted in seven Chinese acute care hospitals. PATIENTS AND INTERVENTION: In total, 1,654 eligible patients were identified, and 1,204 were enrolled in the study. Enrolled patients were randomly assigned into the trial group (4-hour repositioning combined with a viscoelastic foam mattress; n = 602) or the control group (2-hour repositioning combined with a powered air pressure redistribution mattress; n = 602). Participants received their respective protocols until they were discharged, died, or for at least 7 days. MAIN OUTCOME MEASURES: The incidence of PIs, Braden Scale scores, and the time to development of PIs. MAIN RESULTS: Ultimately, 596 trial group patients and 598 control group patients were analyzed. Thirteen patients had single new stage 2 or worse PIs. The total incidence of PIs was 1.1%. The difference between the two groups was significant (0.3% vs 1.8%). However, the difference between the groups' Braden Scale score median during the intervention was not significant (13 vs 13.5). CONCLUSIONS: The 4-hour repositioning interval combined with a viscoelastic foam mattress did not increase PI incidence or risk. These findings could help providers select the right pressure redistribution mattresses and repositioning intervals for critical care patients.

The prevalence, characteristics, and related factors of pressure injury in medical staff wearing personal protective equipment against COVID-19 in China: A multicentre cross-sectional survey.

Since December 2019, the medical staff fighting against COVID-19 frequently reported the device-related pressure injury (DRPI) caused by personal protective equipment (PPE). We conducted a cross-sectional survey online to investigate the prevalence and characteristics of DRPI among medical staff. Univariate and multivariate logistic regression analyses were employed to explore the risk factors associated with DRPI. A total of 4308 participants were collected and 4306 participants were valid from 161 hospitals in China. The overall prevalence of DRPI caused by PPE among medical staff was 30.03% (95% CI 28.69%-31.41%). The prevalence of male was more than that of female (42.25%, 95% CI 37.99-46.51% vs 26.36%, 95% CI 26.93-29.80%, P < .001).The categories were mainly stages 1 and 2, and the common anatomical locations were nose bridge, cheeks, ears, and forehead. Logistic regression analysis revealed that the risk factors were sweating (OR = 43.99, 95% CI 34.46-56.17), male (OR = 1.50, 95% CI 1.12-1.99), level 3 PPE (OR = 1.44, 95% CI 1.14-1.83), and longer wearing time (OR = 1.28, 95% CI 0.97-1.68). The prevalence of DRPI was high among medical staff wearing PPE against COVID-19, and the risk factors were sweating, male, wearing level 3 PPE, and longer wearing time. Comprehensive preventive interventions should be taken.

Pentraxin 3 promotes cardiac differentiation of mouse embryonic stem cells through JNK signaling pathway.

Cardiovascular disease is a leading cause of death worldwide, requiring the development of new therapeutic strategies including stem cell therapy. Pentraxins (PTXs) are a superfamily of proteins highly involved in different myocardial disorders, and thus this study aimed to identify the modulation of long pentraxin 3 (PTX3) in the differentiation of mouse embryonic stem cells (mESCs) toward cardiomyocytes. Cell toxicity of PTX3 was detected by MTT and LDH assays in mESCs. Embryoid bodies (EBs) were differentiated using hanging drop method, and the beating was observed under microscope. Expressional levels of early cardiac progenitor marker genes were assessed by qRT-PCR. Expression of marker proteins in early myocardial development and the activation of JNK signaling pathway was evaluated by Western blot. PTX3 treatment at 50 ng/mL significantly promoted the expression of cardiac-specific marker genes including Nkx2.5, Mef2c, Tbx5, dHand, and αMHC, and increased the expression of cardiac maturity indicative markers including connexin 43 and troponin C1. PTX3 enhanced the phosphorylation of JNK across the incubation duration, whereas the activation of p38 remained the same as control group. Co-treatment of JNK signaling pathway inhibitor SP600125 impaired the PTX3-promoted transcription of Nkx2.5, Mef2c, Tbx5, dHand, and αMHC. This study revealed the promotion of PTX3 in the differentiation of mESCs into cardiomyocytes and the underlying mechanism.

Circadian locomotor output cycles kaput accelerates atherosclerotic plaque formation by upregulating plasminogen activator inhibitor-1 expression.

To explore the association between clock circadian regulator circadian locomotor output cycles kaput gene (CLOCK) and the forming of atherosclerotic plaques and its underlying mechanisms, mouse aortic endothelial cells (MAECs) and atherosclerosis (AS) mouse model were recruited for our study. The apoE gene knockout mouse was used as the model of AS and we accelerated the formation of unstable plaques through the combination of carotid artery ligation and high-fat (HF) diet administration (0.2% cholesterol, 20% fat). The mRNA and protein expressions of CLOCK in peripheral blood monouclear cells of acute coronary syndrome (ACS) patients or mouse AS model were detected by qPCR, western blot analysis and immunohistochemical staining. The number of adherent cells and atherosclerotic plaques was counted to assess the effects of CLOCK on the progression of ACS, and adherence-associated genes, such as vascular cell adhesion molecule (VCAM)-1, C-C motif chemokine ligand 2 (CCL-2), and CCL-5. The results showed that CLOCK expression was significantly increased in both ACS patients and AS mouse model. The levels of CLOCK, leukemia inhibitory factor (LIF), intercellular adhesion molecule 1 (ICAM-1), perilipin 2 (ADFP), nuclear factor kappa B (NF-κB), and plasminogen activator inhibitor-1 (PAI-1), as well as the number of atherosclerotic plaques were elevated in the AS mouse model, as compared with the control group. Chromatin immunoprecipitation assay showed that CLOCK bound directly to the promoter of PAI-1 gene and CLOCK could positively regulate the expressions of LIF, ICAM-1, ADFP, NF-κB, and PAI-1. Reduction of CLOCK expression would decrease the expressions of VCAM-1, CCL-2, and CCL-5, and the number of adherent cells and atherosclerotic plaques, but these effects were neutralized when PAI-1 was simultaneously overexpressed in either mouse model or MAECs. Our results demonstrate that CLOCK overexpression triggers the formation of atherosclerotic plaques by directly upregulating PAI-1 expression.

Care and treatment of a rare Mycobacterium avium complex-infected wound: a case report.

An unusual presentation of Mycobacterium avium complex (MAC), unlikely to be encountered in an outpatient dermatology setting, was diagnosed in a patient without an immunodeficiency. A 47-year-old woman, who was immunocompetent and had no risk factors, presented with a full-thickness, infected wound (large amounts of purulent exudate and severe pain) on her back, which had been present for two months. She was diagnosed as having an MAC infection, using a DNA microarray chip method. The patient underwent wound drainage and a fresh silver-containing dressing was applied daily for two months. Although systemic antibiotics were given for one week and anti-tuberculous medication for one month, there was no response. She also complained of bloating, nausea, loss of appetite and other problems, apparently due to drug-induced liver damage, confirmed by laboratory tests. Based on her characteristics and a literature review related to MAC infection, we implemented an individualised, holistic care protocol for the patient that included a daily diet of appropriate fresh vegetables and fruits, and adequate high-quality protein, aerobic exercises for two hours per day, and sleep for 6-8 hours per day, to alleviate the iatrogenic liver damage, improve immune function and reduce the stress response. The wound continued treatment with sharp debridement as needed, and fresh antimicrobial silver-containing dressings every other day. Wound size was measured once a week to evaluate the effects. The wound healed after 48 days, and the patient was followed-up for 18 months at the outpatient wound care centre and through social media. No recurrence or scar hyperplasia was observed.

Immunization with advanced glycation end products modified low density lipoprotein inhibits atherosclerosis progression in diabetic apoE and LDLR null mice.

BACKGROUND: Diabetes accelerates atherosclerosis through undefined molecular mechanisms. Hyperglycemia induces formation of advanced glycation end product (AGE)-modified low-density lipoprotein (LDL). Anti-AGE-LDL autoantibodies favor atherosclerosis (AS) progression in humans, while anti oxidized LDL immunization inhibits AS in hypercholesterolemic, non-diabetic mice. We here investigated if AGE-LDL immunization protects against AS in diabetic mice. METHODS: After diabetes induction with streptozotocin and high fat diet, both low density lipoprotein receptor (LDLR)-/- and apoE female mice were randomized to: AGE-LDL immunization with aluminum hydroxide (Alum) adjuvant; Alum alone; or PBS. RESULTS: AGE-LDL immunization: significantly reduced AS; induced specific plasma IgM and IgG antibodies; upregulated splenic Th2, Treg and IL-10 levels, without altering Th1 or Th17 cells; and increased serum high density lipoprotein(HDL) while numerically lowering HbA1c levels. CONCLUSIONS: Subcutaneous immunization with AGE-LDL significantly inhibits atherosclerosis progression in hyperlipidemic diabetic mice possibly through activation of specific humoral and cell mediated immune responses and metabolic control improvement.

Immunochromatographic enhancement strategy for SARS-CoV-2 detection based on nanotechnology.

The global outbreak of coronavirus disease 2019 (COVID-19) has been catastrophic to both human health and social development. Therefore, developing highly reliable and sensitive point-of-care testing (POCT) for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a priority. Among all available POCTs, the lateral flow immunoassay (LFIA, also known as immunochromatography) has proved to be effective due to its accuracy, portability, convenience, and speed. In areas with a scarcity of laboratory resources and medical personnel, the LFIA provides an affordable option for the diagnosis of COVID-19. This review offers a comprehensive overview of methods for improving the sensitivity of SARS-CoV-2 detection using immunochromatography based on nanotechnology, sorted according to the different detection targets (antigens, antibodies, and nucleic acids). It also looks into the performance and properties of the various sensitivity enhancement strategies, before delving into the remaining challenges in COVID-19 diagnosis through LFIA. Ultimately, it seeks to provide helpful guidance in selecting an appropriate strategy for SARS-CoV-2 immunochromatographic detection based on nanotechnology.

The effect of ozone short-term exposure on flow-mediated dilation: Using data before and after COVID-19 lockdown in Shanghai.

BACKGROUND: Short-term ambient ozone exposure has been shown to have an adverse impact on endothelial function, contributing to major cardiovascular diseases and premature death. However, only limited studies have focused on the impact of short-term ozone exposure on Flow-mediated Dilation (FMD), and their results have been inconsistent. The current study aims to explore the relationship between short-term ambient ozone exposure and FMD. In addition, the study aims to investigate how lockdown measures for COVID-19 may influence ozone concentration in the atmosphere. METHODS: Participants were recruited from a hospital in Shanghai from December 2020 to August 2022. Individuals' ozone exposure was determined using residential addresses. A distributed lag nonlinear model was adopted to assess the exposure-response relationship between short-term ozone exposure and FMD. A comparison was made between ambient ozone concentration and FMD data collected before and after Shanghai's lockdown in 2022. RESULTS: When ozone concentration was between 150 and 200 µg/m3, there was a significant reduction in FMD with a 2-day lag. Elderly individuals (age ≥ 65), females, non-drinkers, and non-smokers were found to be more susceptible to high concentrations of ozone exposure. The lockdown did elevate ambient ozone concentration compared to the same period previously. INTERPRETATION: This study proposes that an ambient ozone concentration of 150-200 µg/m3 is harmful to endothelial function, and that a reduction in human activity during lockdown increased the concentration, which in turn reduced FMD. However, the underlying mechanism requires further research.

Myocardial bridging is a potential risk factor of very late stent thrombosis of drug eluting stent.

Drug eluting stents have been implanted worldwide and used in nearly 90% of percutaneous coronary interventions in China. Although many randomized trials have confirmed the efficacy and safety profile of drug eluting stents, they were not powered to detect or exclude the effect of drug eluting stents on rare events such as stent thrombosis. Several mechanisms of very late stent thrombosis have been postulated, but are not widely accepted. Virchow's triad describes the 3 main factors of thrombus formation - stasis of blood flow, endothelial injury and hypercoagulability. Myocardial bridging is a common congenital anomaly. Modern anatomy and angiography regard myocardial bridging as widespread, but its pathophysiological response is always ignored. According to Virchow's triad, myocardial bridging negatively affect endothelial function, and the turbulent shear stress and intimal trauma predispose the vessel toward thrombus formation. Therefore, we question whether a relationship between myocardial bridging and very late stent thrombosis of drug eluting stents exists. Also, we propose that myocardial bridging might be a potential risk factor of very late stent thrombosis of drug eluting stents; coronary artery bypass grafting might be a promising and novel choice in the treatment of myocardial bridging with severe stenosis in the coronary artery.

Prevalence and associated factors of dry skin among older inpatients in hospitals and nursing homes: A multicenter cross-sectional study.

BACKGROUND/OBJECTIVES: Dry skin is a common skin problem in older persons. Aim of this study was to determine the prevalence, associated factors of dry skin in older inpatients. DESIGN: A multicenter cross-sectional study was designed and conducted. SETTINGS/PARTICIPANTS: On 31 March and 29 May in 2021 two days, fifty hospitals and two nursing homes in China participated in the study. In total, 33,769 participants were included. The mean age was 73.2 (SD 8.9) years. METHODS: A whole-body skin examination and associated data collection were performed by 1067 trained nurses based on a standardized data form and methods. Descriptive and univariable analyses and multivariable logistic regressions were conducted. RESULTS: In total, 11,602 participants had dry skin with a prevalence of 34.4%, mainly located on the upper and lower limbs with very severe skin dryness, 21.2% of the participants reported that their dry skin had pruritus, and 12.5% complained that sleep was affected by dry skin. The stronger predictor for dry skin was nursing homes (OR 5.07, 95% CI 3.99-6.45). Other predictors for dry skin were age, male sex, nutrition, lower activity level, skincare dependence, renal and pulmonary impairment, diabetes mellitus, varicose veins, cardiovascular diseases and Parkinsonism, diuretics, statins and antibiotics. The predictive model of area under ROC curve was 0.628(95% CI 0.622-0.634). CONCLUSIONS: The prevalence of dry skin among Chinese older patients was at high level and was associated with multiple factors. Persons with skin dryness have a higher proportion of skin itching and poor sleep. REGISTRATION: It has been registered in the Chinese Clinical Trial Registry (ChiCTR2100042893).

Methylation of adrenergic ß1 receptor is a potential epigenetic mechanism controlling antihypertensive response to metoprolol.

Although metoprolol is used to treat hypertension, clinical responses are variable and unpredictable. Evidence suggests that adrenergic beta1 receptor (ADRB1, designated Adrb1 in rodents) gene polymorphisms influence the level of blood pressure response to this drug therapy, but their presence can not predict the response of the individual patient. The question exists whether epigenetic modifications, such as DNA methylation could cause changes in the gene's expression that are a determining factor in metoprolol's efficacy. The aim of this study was to verify whether DNA methylation could change the expression of the ADRB1 gene, and epigenetic modification could explain why individuals with identical ADRB1 gene polymorphisms have different antihypertensive responses to metoprolol. H9c2 rat myocardial cells in vitro were randomly divided into 5-aza-2'-deoxycytidine (decitabine)-treated (0.5 to 10.0 microM) and control groups. For the in vivo experiments, 45 spontaneously hypertensive rats (SHRs) were divided into metoprolol-treated and control groups, and after a 4-week intervention myocardia were harvested. Genomic methylation-sensitive PCR was used to assess the methylation status of the Adrb1 promoter after DNA extraction from H9c2 cells and SHR myocardia. Real-time fluorescent quantitative RT-PCR was used to determine levels ofAdrb1 mRNA. In H9c2 cells, the least degree of methylation was observed in the 5.0 microM decitabine treated group. Prolonged exposure of cells to 5.0 microM decitabine resulted in downregulating methylation of the Adrb1 promoter. Increased levels of Adrb1 mRNA of the 5.0 microM group demonstrated that this concentration resulted in the highest expression. Accordingly, DNA methylation resulted in the downregulation of Adrb1 transcription. In vivo, the lower level of methylation of the Adrb1 promoter from SHR myocardial samples demonstrated a better antihypertensive effect by metoprolol. The expression of Adrb1 mRNA in the effective group of SHRs was significantly upregulated. In conclusion, as shown in both H9c2 cells and SHRs, downregulated methylation of the Adrb1 promoter is likely to improve the antihypertensive efficacy of metoprolol.

LINC00668 cooperated with HuR dependent upregulation of PKN2 to facilitate gastric cancer metastasis.

In China, gastric cancer (GC) ranks first in the incidence of all malignant tumors. With high recurrence and distant metastasis, GC has caused considerable mortalities. LncRNA long intergenic non-protein-coding RNA 668 (LINC00668) has been reported to be upregulated in GC cells and predict poor prognosis of GC patients. However, the mechanism of LINC00668 has not been fully investigated in GC. This study aimed to investigate the role of LINC00668 in GC. We found that LINC00668 level was upregulated in GC tissue and cells and predicted poor prognosis. Functionally, LINC00668 knockdown suppressed GC cell migration and invasion. Additionally, LINC00668 knockdown inhibited epithelial to mesenchymal transition (EMT) process. PKN2 exerts similar effects with LINC00668 in GC cells. LINC00668 knockdown suppressed tumor growth and metastasis in vivo. Mechanistically, HuR was predicted to bind with LINC00668 and protein kinase N2 (PKN2). RNA pull-down assays validated the binding between HuR and LINC00668 (or PKN2). Moreover, either silencing of LINC00668 or HuR could decrease PKN2 mRNA stability or reduce PKN2 mRNA and protein levels. Furthermore, PKN2 expression was positively correlated with LINC00668 expression and HuR expression in GC tissues, and HuR expression was positively associated with LINC00668 expression in GC tissues. Finally, rescue assays confirmed that the suppressive effect of LINC00668 silencing on cell migration, invasion, and EMT process was reversed by PKN2 overexpression or HuR upregulation. In conclusion, LINC00668 cooperated with HuR-dependent upregulation of PKN2 to facilitate gastric cancer metastasis, which may provide a potential novel insight for GC treatment.