Emerging applications of single-cell profiling in precision medicine of atherosclerosis.

Atherosclerosis is a chronic, progressive, inflammatory disease that occurs in the arterial wall. Despite recent advancements in treatment aimed at improving efficacy and prolonging survival, atherosclerosis remains largely incurable. In this review, we discuss emerging single-cell sequencing techniques and their novel insights into atherosclerosis. We provide examples of single-cell profiling studies that reveal phenotypic characteristics of atherosclerosis plaques, blood, liver, and the intestinal tract. Additionally, we highlight the potential clinical applications of single-cell analysis and propose that combining this approach with other techniques can facilitate early diagnosis and treatment, leading to more accurate medical interventions.

A Cross-Sectional Study of Risk Factors for Coronary Heart Disease in Secondary Prevention for Patients With the Disease in China.

AIMS: To explore risk factors for Coronary Heart Disease (CHD) in secondary prevention for patients with the disease in China. DESIGN: Cross-sectional study. METHODS: A two-stage sampling method was used (stratified sampling and systematic sampling). Patients who met WHO diagnostic criteria for CHD, had the capacity to give informed consent and volunteered to participate were recruited from five districts in Hengyang city, Hunan province, China. Six instruments were used: A general socio-demographic questionnaire, Coronary Heart Disease Self-Management Scale, International Physical Activity Questionnaires, Chinese Eight-Item Morisky Medication Adherence Scale, Zung's Self-Rating Anxiety Scale and Sexual Health Questionnaires. Participants completed the questionnaires in person or via telephone. Single-factor correlation analysis, Pearson correlation analysis and multiple linear regression analysis were carried out. RESULTS: A total of 373 patients were recruited with a mean age of 66.25 years (standard deviation = 9.98). The mean score was 57.00 (14.23) for self-management, 5.41 (1.82) for medication adherence, 53.61 (9.26) for anxiety, 8.66 (3.18) for sexual knowledge and 22.20 (9.68) for the need for sexual health education. The median was 1563.90 MET-min/day for total energy consumption of physical activity. Self-management, physical activity, medication adherence, anxiety and sexual health were significantly correlated with a range of demographic variables (age, gender, marital status, occupation, education levels, types of medical insurance, personal monthly income, living arrangements) and illness-related variables (illness duration, number of hospital admissions, type of therapy, number of other chronic diseases, cardiac function grading and BMI). CONCLUSION: This research has showed the risk factors related to self-management skills, medication adherence, anxiety, physical activity, sexual knowledge and the need for sexual health education in secondary prevention for patients with CHD. Health professionals play an important role in helping patients reduce risk factors for CHD to minimise its reoccurrence and mortality. RELEVANCE TO CLINICAL PRACTICE: Both hospital-based and community-based health professionals, especially nurses, have an important role to play in developing and implementing health promotion interventions to help patients with CHD reduce risk factors for the disease and thus reduce mortality. PATIENT OR PUBLIC CONTRIBUTION: No patient contribution. Community nursing staff contributed to the design of the general socio-demographic questionnaire for this study. REPORTING METHOD: The STROBE checklist was used to ensure comprehensive reporting (Appendix S1).

The Role of Circular RNAs in Ischemic Stroke.

Ischemic stroke (IS), a devastating condition characterized by intracranial artery stenosis and middle cerebral artery occlusion leading to insufficient oxygen supply to the brain, is a major cause of death and physical disability worldwide. Recent research has demonstrated the critical role of circular RNAs (circRNAs), a class of covalently enclosed noncoding RNAs that are widespread in eukaryotic cells, in regulating various physiological and pathophysiological cellular processes, including cell apoptosis, autophagy, synaptic plasticity, and neuroinflammation. In the past few years, circRNAs have attracted extensive attention in the field of IS research. This review summarizes the current understanding of the mechanisms underlying the involvement of circRNAs in IS development. A better understanding of circRNA-mediated pathogenic mechanisms in IS may pave the way for translating circRNA research into clinical practice, ultimately improving the clinical outcomes of IS patients.

Secondary prevention of coronary heart disease: The effect of a nursing intervention using Cox's interaction model of client health behaviour.

AIMS: Secondary prevention of coronary heart disease is of utmost importance to facilitate people to achieve health outcomes and behaviours. This study was to investigate the effect of a nursing intervention based on Cox's interaction model of client health behaviour to improve health outcomes and behaviours of secondary prevention of coronary heart disease. DESIGN: This study is a cluster randomised controlled trial. METHODS: Participants were recruited between August and November 2019 in two community settings in Hengyang city, Hunan province, China. Participants in the intervention group received a nursing intervention based on Cox's interaction model of client health behaviour and routine health education, while those in the control group received routine health education only. The outcome variables included self-management, physical activity, medication compliance, anxiety, sexual knowledge, the ability to identify sexual health education needs, blood pressure, body mass index (BMI), and low-density lipoprotein cholesterol (LDL-C). The influential statistical tests applied to analyse the data included χ2 tests and t tests. RESULTS: Seventy-seven participants completed this study. Compared with the control group (n = 40), the intervention group (n = 37) showed statistically significant better health outcomes and behaviours regarding self-management, physical activity (except for high energy consumption), medication compliance, anxiety, sexual knowledge, the ability to identify sexual health education needs, systolic blood pressure, BMI, and LDL-C. However, there was no statistically significant difference in diastolic blood pressure and high energy consumption for physical activity. CONCLUSION: A well-developed nursing intervention based on Cox's interaction model of client health behaviour could successfully improve health outcomes and behaviours of secondary prevention of coronary heart disease. Such an intervention may be incorporated into community healthcare practice by nurses to improve patient care. IMPACT: This study provides a valuable insight to facilitate further development of effective nursing interventions to improve secondary prevention of coronary heart disease in community settings.

The Effect of Resourcefulness Training on Depression and Coping Styles of Patients With Coronary Heart Disease in China [RETRACTED].

BACKGROUND: Coronary heart disease (CHD) is one of the leading causes of mortality worldwide. Previous research has demonstrated that resourcefulness interventions can help individuals identify effective coping strategies to manage their conditions, reduce the incidence of depression, and improve their quality of life. However, little is known about such interventions for people with CHD in China. OBJECTIVE: This study aimed to investigate the effects of a resourcefulness training intervention on depression and coping style of patients with CHD in China. METHODS: A cluster randomized controlled trial design was used. A convenience sample of 72 patients in community settings took part in the study. Participants in the intervention group (n = 36) received an 8-week intervention based on the concept of resourcefulness, plus routine health education. Participants in the control group (n = 36) received routine health education only. Three outcomes (resourcefulness, depression, and coping styles) were measured using the Resourcefulness Scale, Center for Epidemiological Studies Depression Scale, and Medical Coping Mode Questionnaire. Data were collected at baseline and post intervention, and analyzed using frequencies, percentages, means, standard deviations, independent sample t tests, and χ tests. RESULTS: After the intervention, participants in the intervention group had significantly higher scores on resourcefulness and coping styles, and lower scores on depression than those in the control group (both Ps < .001). CONCLUSIONS: It is suggested that a well-developed resourcefulness intervention could help patients with CHD in China and beyond to be more resourceful, improve their level of depression, and choose more effective strategies to cope with stress.

Development and validation of a Chinese-language instrument measuring empowerment needs of patients after a percutaneous coronary intervention.

Patient empowerment has been shown to have some positive impacts on self-efficacy, self-esteem, and recovery. However, information about the empowerment needs of patients after a percutaneous coronary intervention is scarce. The aim of this study was to develop a Chinese-language instrument to measure empowerment needs of such patients. The initial instrument was generated based on a literature review and interviews with patients after a percutaneous coronary intervention procedure. Content validity was tested with a panel of experts using the Delphi method. In total, 226 patients were recruited for psychometric tests using the revised instrument. Expert authority coefficient was 0.92, and content validity index was 0.95. The internal consistency reliability was demonstrated by Cronbach's α coefficients (0.86 for the total score, 0.66-0.74 for the dimensions). The newly developed 19-item, five-dimension instrument has shown satisfactory validity (face/content validity and construct validity) and internal consistency reliability. The instrument could help clinical nurses who have close contact with patients after a percutaneous coronary intervention to gain a better understanding of their empowerment needs and could help develop appropriate health education to address such needs.

Nobiletin reduces LPL-mediated lipid accumulation and pro-inflammatory cytokine secretion through upregulation of miR-590 expression.

Nobiletin has protective effects on cardiovascular diseases, but the mechanism is not clear. In this study, we examined whether nobiletin affects the expression of miR-590/LPL and its relative effects on lipid accumulation and pro-inflammatory cytokine secretion in human THP-1 macrophages. RT-qPCR analysis showed that nobiletin increased the expression of miR-590. Western blot analysis showed that nobiletin-suppressed LPL expression was enhanced by miR-590 mimic and abrogated by miR-590 inhibitor. Oil Red O staining and high-performance liquid chromatography assays showed that nobiletin attenuated lipid accumulation in macrophages. Treatment with nobiletin and miR-590 mimic decreased cellular lipid accumulation, whereas treatment with miR-590 inhibitor increased cellular lipid accumulation. ELISA illustrated that nobiletin alleviated pro-inflammatory cytokine secretion in macrophages as measured by, which was reduced by miR-590 mimic and increased by miR-590 inhibitor. In conclusion, nobiletin may alleviate lipid accumulation and secretion of pro-inflammatory cytokines by enhancing the inhibitory effect of miR-590 on LPL expression, suggesting a promising strategy for potential drug development for atherosclerosis.

MicroRNA-296: a promising target in the pathogenesis of atherosclerosis?

Atherosclerosis has been recognized as an inflammatory disease involving the vascular wall. MicroRNAs are a group of small noncoding RNAs to regulate gene expression at the transcriptional level through mRNA degradation or translation repression. Recent studies suggest that miR-296 may play crucial roles in the regulation of angiogenesis, inflammatory response, cholesterol metabolism, hypertension, cellular proliferation and apoptosis. In this review, we primarily discussed the molecular targets of miR-296 involved in the development of atherosclerosis, which may provide a basis for future investigation and a better understanding of the biological functions of miR-296 in atherosclerosis.

Visceral adipose tissue-derived serine protease inhibitor accelerates cholesterol efflux by up-regulating ABCA1 expression via the NF-κB/miR-33a pathway in THP-1 macropahge-derived foam cells.

Atherosclerosis is a dyslipidemia disease characterized by foam cell formation driven by the accumulation of lipids. Visceral adipose tissue-derived serine protease inhibitor (vaspin) is known to suppress the development of atherosclerosis via its anti-inflammatory properties, but it is not yet known whether vaspin affects cholesterol efflux in THP-1 macrophage-derived foam cells. Here, we investigated the effects of vaspin on ABCA1 expression and cholesterol efflux, and further explored the underlying mechanism. We found that vaspin decreased miR-33a levels, which in turn increased ABCA1 expression and cholesteorl efflux. We also found that inhibition of NF-κB reduced miR-33a expression and vaspin suppressed LPS-mediated NF-κB phosphorylation. Our findings suggest that vaspin is not only a regular of inflammasion but also a promoter of cholesterol efflux.

miR-758-5p regulates cholesterol uptake via targeting the CD36 3'UTR.

miR-758-3p plays an important role via regulting ABCA1-mediated cholesterol efflux in atherosclerosis. However, the mechanism of miR-758-5p in cholesterol metabolism is still unclear. Here, we revealed that miR-758-5p decreased total cholesterol accumulation in THP-1 macrophage derived foam cells through markedly reducing cholesterol uptake, and no effect on the cholesterol efflux. Interestingly, computational analysis suggests that CD36 may be a target gene of miR-758-5p. Our study further demonstrated that miR-758-5p decreased CD36 expression at both protein and mRNA levels via targeting the CD36 3'UTR in THP-1 macrophage derived foam cells. The present present study concluded that miR-758-5p decreases lipid accumulation of foam cell via regulating CD36-mediated the cholesterol uptake. Therefore, targeting miR-758-5p may offer a promising strategy to treat atherosclerotic vascular disease.

MicroRNA-182 Promotes Lipoprotein Lipase Expression and Atherogenesisby Targeting Histone Deacetylase 9 in Apolipoprotein E-Knockout Mice.

BACKGROUND: Lipoprotein lipase (LPL) expressed in macrophages plays an important role in promoting the development of atherosclerosis or atherogenesis. MicroRNA-182 (miR-182) is involved in the regulation of lipid metabolism and inflammation. However, it remains unclear how miR-182 regulates LPL and atherogenesis.Methods and Results:Using bioinformatics analyses and a dual-luciferase reporter assay, we identified histone deacetylase 9 (HDAC9) as a target gene of miR-182. Moreover, miR-182 upregulated LPL expression by directly targetingHDAC9in THP-1 macrophages. Hematoxylin-eosin (H&E), Oil Red O and Masson's trichrome staining showed that apolipoprotein E (ApoE)-knockout (KO) mice treated with miR-182 exhibited more severe atherosclerotic plaques. Treatment with miR-182 increased CD68 and LPL expression in atherosclerotic lesions in ApoE-KO mice, as indicated by double immunofluorescence staining in the aortic sinus. Increased miR-182-induced increases in LPL expression in ApoE-KO mice was confirmed by real-time quantitative polymerase chain reaction and western blotting analyses. Treatment with miR-182 also increased plasma concentrations of proinflammatory cytokines and lipids in ApoE-KO mice. CONCLUSIONS: The results of the present study suggest that miR-182 upregulates LPL expression, promotes lipid accumulation in atherosclerotic lesions, and increases proinflammatory cytokine secretion, likely through targetingHDAC9, leading to an acceleration of atherogenesis in ApoE-KO mice.

Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens.

Organophosphate-induced delayed neuropathy (OPIDN) is pathologically characterized by the swollen axon containing aggregations of microtubules, neurofilaments, smooth endoplasmic reticulum and multivesicular vesicles. At present, the exact mechanism of OPIDN is unclear and the effective therapeutic methods is not available to counter this syndrome. Recent studies had shown that the autophagy was involved in OPIDN. The adipocytokine Apelin is a peptide, Apelin and its receptor are abundantly expressed in the nervous system. Recent researches illuminated that Apelin was neuroprotective factor and Apelin could regulate the autophagy in vivo and vitro model. So we investigated the effect of Apelin-13 on the OPIDN induced by Tri-ortho-cresyl phosphate (TOCP) in hens and explored the role of autophagy in Apelin-13 preventing OPIDN. Adult Roman hens were given a single dose of 750 mg/kg TOCP by gavage for 21 days to induce OPIDN, and neural dysfunction were detected, and the formation of autophagosomes in spinal cord neurons was observed by transmission electron microscopy, and the molecular markers of autophagy microtubule-associated protein light chain-3 (LC3) and the autophagy substrates p62/SQSTM1 were determined by Western blot analysis. The results demonstrated that the obvious neurological dysfunction such as hindlimb paralysis and paralysis of gait was present, the number of autophagosomes in the neurons of spinal cords was significantly increased, the level of LC3-II and p62 expressions and the ratio of LC3-II/LC3-I in spinal cords and sciatic nerve were significantly increased in the OPIDN model group compared with the control group. Compared with the OPIDN model group, the neurological dysfunction of tens was obviously reduced, the clinical signs scores was significantly decreased, the number of autophagosomes in the neurons of hen spinal cords was significantly decreased, the level of LC3-II and p62 expressions and the ratio of LC3-II/LC3-I in spinal cords and sciatic nerve were significantly decreased in Apelin-13 treatment group. Our results suggested that Apelin-13 prevented against the OPIDN induced by TOCP in hens, which the mechanism might be associated with regulation autophagy flux by Apelin-13.

Microwave-assisted oxidative digestion of lignin with hydrogen peroxide for TOC and color removal.

Dilute lignin solution was successfully digested into colorless and clarified liquor under microwave-assisted oxidative digestion with hydrogen peroxide. High dosage of hydrogen peroxide is needed to effectively digest lignin, but excessive hydrogen peroxide may lead to recondensation of formed fragments in digested lignin. Microwave irradiation greatly facilitates the oxidative digestion of lignin. Compared with conventional heating technique, microwave-assisted digestion achieves the same or higher digestion rate within a shorter time and/or at lower temperature. After digestion, total organic carbon content of lignin solution decreases by 93.9%, and a small amount of aliphatic alkane, alcohol, acid and ester are formed via the cleavage of aromatic rings as well as the deprivation of side chains in original lignin. This work provides an alternative way to efficiently treat spent pulping liquor.

Growth differentiation factor-15 induces expression of ATP-binding cassette transporter A1 through PI3-K/PKCζ/SP1 pathway in THP-1 macrophages.

OBJECTIVE: The aim of this study was to determine whether ATP-binding cassette transporter A1 (ABCA1) was up-regulated by growth differentiation factor-15 (GDF-15) via the phosphoinositide 3-kinase (PI3K)/protein kinase Cζ (PKCζ)/specificity protein 1 (SP1) pathway in THP-1 macrophages. METHODS AND RESULTS: We investigated the effects of different concentrations of GDF-15 on ABCA1 expression in THP-1 macrophages. The results showed that GDF-15 dramatically increased cholesterol efflux and decreased cellular cholesterol levels. In addition, GDF15 increased ABCA1 mRNA and protein levels. The effects of GDF-15 on ABCA1 protein expression and cellular cholesterol efflux were abolished by wither inhibition or depletion of PI3K, PKCζ and SP1, respectively, suggesting the potential roles of PI3K, PKCζ and SP1 in ABCA1 expression. Taken together, GDF-15 appears to activate PI3K, PKCζ and SP1 cascade, and then increase ABCA1 expression, thereby promoting cholesterol efflux and reducing foam cell formation. CONCLUSION: Our results suggest that GDF-15 has an overall protective effect on the progression of atherosclerosis, likely through inducing ABCA1 expression via the PI3K/PKCζ/SP1 signaling pathway and enhancing cholesterol efflux.

Interleukin-27 inhibits foam cell formation by promoting macrophage ABCA1 expression through JAK2/STAT3 pathway.

The purpose of this study is to determine whether IL-27 regulates macrophage ABCA1 expression, foam cell formation, and also explore the underlying mechanisms. Here, we revealed that IL-27 decreased lipid accumulation in THP-1 derived macrophages through markedly enhancing cholesterol efflux and increasing ABCA1 expression at both protein and mRNA levels. Our study further demonstrated that IL-27 increased ABCA1 level via activation of signal transducer and activator of transcription 3 (STAT3). Inhibition of Janus kinase 2, (JAK2)/STAT3 suppressed the stimulatory effects of IL-27 on ABCA1 expression. The present study concluded that IL-27 reduces lipid accumulation of foam cell by upregulating ABCA1 expression via JAK2/STAT3. Therefore, targeting IL-27 may offer a promising strategy to treat atherosclerotic vascular disease.

Advanced oxidation protein products exacerbates lipid accumulation and atherosclerosis through downregulation of ATP-binding cassette transporter A1 and G1 expression in apolipoprotein E knockout mice.

BACKGROUND: Both clinical data and basic science studies suggest that advanced oxidation protein products (AOPPs) may contribute to the progression of atherosclerosis. The aim of this study was to investigate the effects of AOPPs on ATP-binding cassette transporter (ABC) A1 and ABCG1 expression, lipid accumulation and atherosclerotic lesions in apolipoprotein E knockout (apoE-KO) mice. METHODS AND RESULTS: Male 8-week-old apoE-KO mice were fed a high-fat/high-cholesterol diet. Mice received intraperitoneal injections of AOPPs (5 mg/kg) and/or Janus Kinase (JAK) inhibitor AG-490 (5 mg/kg) once every other day for 8 weeks. As shown in our data, AOPPs increased lipid levels of plasma, and promoted advanced lesions in the aortic regions in apoE-KO mice. The ABCA1, ABCG1 and liver X receptor alpha (LXRα) expression were downregulated in apoE-KO mice treated with AOPPs, whereas the lesions in the aortas were decreased, and the ABCA1, ABCG1 and LXRα expression were upregulated in mice treated with AOPPs plus AG-490, compared to the mice treated with AOPPs only. The ABCA1 and LXRα expressions of aortas, liver and intestine were downregulated in the AOPPs group, while the expressions were upregulated in the AOPPs-plus-AG-490 group when compared to the AOPPs group. The same results can be also observed in peritoneal macrophages. CONCLUSIONS: AOPPs increase accumulation of lipids and exacerbate atherosclerosis through downregulation of ABCA1 and ABCG1 expression, and the JAK-LXRα signaling pathway in apoE-KO mice.

Effects of a PRECEDE-PROCEED Model-Based Intervention on Fatigue in Patients With Coronary Heart Disease: A Randomized Controlled Trial.

OBJECTIVE: This research aimed to determine how a 12-week PRECEDE-PROCEED model-based intervention affected fatigue in patients with coronary heart disease. METHODS: This cluster randomized controlled trial recruited participants diagnosed with coronary heart disease at 2 community health centers in China. Participants in the control group (n = 36) received routine health education, whereas those in the intervention group (n = 38) were given a 12-week PRECEDE-PROCEED model-based intervention and routine health education. The intervention consisted of 6 training sessions on coronary heart disease, fatigue, fatigue management, self-management skills and social support. A primary outcome (fatigue) and 4 secondary outcomes (knowledge of fatigue, self-management, quality of life and body mass index) were assessed using the Fatigue Scale-14, Fatigue Cognitive Questionnaire for Patients with Coronary Heart Disease, Coronary Artery Disease Self-Management Scale, Chinese Cardiovascular Questionnaire of Quality of Life, and electronic weighing scale, respectively. Data were collected 3 times over 12 weeks. RESULTS: Compared with the control group, the intervention group showed a statistically significant improvement in the level of fatigue (8.72 vs 7.06, P < .001), knowledge of fatigue (P < .001), self-management skills (P < .001), and quality of life (P < .001). However, there was no significant difference in body mass index between the 2 groups (P = .504). CONCLUSIONS: The findings suggest that a well-designed intervention based on the PRECEDE-PROCEED model could alleviate fatigue symptoms and increase knowledge of fatigue, self-management skills and quality of life in patients with coronary heart disease.

A novel melatonin agonist Neu-P11 facilitates memory performance and improves cognitive impairment in a rat model of Alzheimer' disease.

Previous studies have shown that melatonin is implicated in modulating learning and memory processing. Melatonin also exerts neuroprotective activities against Aß-induced injury in vitro and in vivo. Neu-P11 (piromelatine, N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-4-oxo-4H-pyran-2-carboxamide) is a novel melatonin (MT1/MT2) receptor agonist and a serotonin 5-HT1A/1D receptor agonist recently developed for the treatment of insomnia. In the present study we firstly investigated whether Neu-P11 and melatonin enhance memory performance in the novel object recognition (NOR) task in rats, and then assessed whether Neu-P11 and melatonin improve neuronal and cognitive impairment in a rat model of Alzheimer' disease (AD) induced by intrahippocampal Aß(1-42) injection. The results showed that a single morning or afternoon administration of Neu-P11 enhanced object recognition memory measured at 4 or 24h after training. Melatonin was effective in the memory facilitating effects only when administered in the afternoon. Further results showed that intrahippocampal Aß(1-42) injection resulted in hippocampal cellular loss, as well as decreased learning ability and memory in the Y maze and NOR tasks in rats. Neu-P11 but not melatonin attenuated cellular loss and cognitive impairment in the rat AD model. The current data suggest that Neu-P11 may serve as a novel agent for the treatment of AD.