Xinbao Pill ameliorates heart failure via regulating the SGLT1/AMPK/PPARα axis to improve myocardial fatty acid energy metabolism.

BACKGROUND: Heart failure (HF) is characterized by a disorder of cardiomyocyte energy metabolism. Xinbao Pill (XBW), a traditional Chinese medicine formulation integrating "Liushen Pill" and "Shenfu Decoction," has been approved by China Food and Drug Administration for the treatment of HF for many years. The present study reveals a novel mechanism of XBW in HF through modulation of cardiac energy metabolism. METHODS: In vivo, XBW (60, 90, 120 mg/kg/d) and fenofibrate (100 mg/kg/d) were treated for six weeks in Sprague-Dawley rats that were stimulated by isoproterenol to induce HF. Cardiac function parameters were measured by echocardiography, and cardiac pathological changes were assessed using H&E, Masson, and WGA staining. In vitro, primary cultured neonatal rat cardiomyocytes (NRCMs) were induced by isoproterenol to investigate the effects of XBW on myocardial cell damage, mitochondrial function and fatty acid energy metabolism. The involvement of the SGLT1/AMPK/PPARα signalling axis was investigated. RESULTS: In both in vitro and in vivo models of ISO-induced HF, XBW significantly ameliorated cardiac hypertrophy cardiac fibrosis, and improved cardiac function. Significantly, XBW improved cardiac fatty acid metabolism and mitigated mitochondrial damage. Mechanistically, XBW effectively suppressed the expression of SGLT1 protein while upregulating the phosphorylation level of AMPK, ultimately facilitating the nuclear translocation of PPARα and enhancing its transcriptional activity. Knockdown of SGLT1 further enhanced cardiac energy metabolism by XBW, while overexpression of SGLT1 reversed the cardio-protective effect of XBW, highlighting that SGLT1 is probably a critical target of XBW in the regulation of cardiac fatty acid metabolism. CONCLUSIONS: XBW improves cardiac fatty acid energy metabolism to alleviate HF via SGLT1/AMPK/PPARα signalling axis.

Label-free fluorescence platform based on SiO2-coated CdTeS quantum dots for trace analysis of Ag+ in environmental water.

In this study, a core-shell structural nano-composite material, namely CdTeS@SiO2, is synthesized by a simple silanization of Te-doped CdS quantum dots (CdTeS QDs). Through SiO2 capping, CdTeS QDs not only improve the fluorescence performance effectively, but also greatly enhance the anti-interference ability in the environment. Based on its excellent optical properties, a novel fluorescence sensor is constructed for the ultramicro detection of Ag+. The fluorescence of CdTeS@SiO2 is strongly quenched in the presence of Ag+ and shows good linearity in the range of 0.005-5.0 µmol L-1 with a detection limit as low as 1.6 nmol L-1. This is mainly due to its unique quenching mechanism: Ag+ destroys the spherical structure of SiO2 and promotes the formation of non-radiative electron-hole pairs through electron transfer, leading to fluorescence quenching. At the same time, it competes with Cd for Te, S and MPA on the CdTeS surface, forming Ag-Te, Ag-S and Ag-MPA complexes attached to the CdTeS surface leading to wavelength red-shift. The feasibility of the proposed sensor is demonstrated through spiking experiments, which confirmed the potential value of the constructed fluorescence probe for real-world applications in detecting Ag+ in environmental water.

New insights on scandium separation from scandium concentrate with titanium dioxide wastewater.

In this study, a scandium concentrate with Sc2O3 content of 66.24 g/t was obtained from V-Ti magnetite tailings by physical concentration, and the main Sc-bearing minerals were augite and hornblende. A novel process of roasting and leaching was proposed to extract scandium from scandium concentrate with titanium dioxide wastewater. Scandium concentrate was pretreated by roasting, and titanium dioxide wastewater was used to directly leach scandium from the roasted ore. The effects of roasting and leaching parameters such as roasting temperature, roasting time, roasting agents, leaching temperature, leaching time, liquid-to-solid ratio, and leaching agents on scandium separation were thoroughly researched in the experimental procedure. The results show that a scandium leaching efficiency of 85.89% was obtained, and the scandium content of leaching residue decreased to 9.31 g/t under the optimal conditions: a roasting temperature of 1123 K, a roasting time of 120 min, a leaching temperature of 343 K, a leaching time of 120 min, and a m (titanium dioxide wastewater)∶m (roasted ore)∶m (ammonium fluoride) ratio of 8∶1∶0.09. The main findings of the scandium separation mechanism show that Sc-bearing minerals can effectively decompose and release scandium element after roasting, and created favorable conditions for scandium leaching with titanium dioxide wastewater to achieve the purpose of scandium recovery.

A graphitic C3N4 nanocomposite-based fluorescence platform for label-free analysis of trace mercury ions.

In this study, a nanocomposite consisting of graphitic carbon nitride nanosheets loaded with graphitic carbon nitride quantum dots (CNQDs/CNNNs) was synthesized via a one-step pyrolysis method. This nanocomposite exhibited excellent thermal stability, photobleaching and salt resistance. Then a new fluorescence sensing platform based on CNQDs/CNNNs was constructed, which showed high sensitivity and selectivity towards trace mercury ions (Hg2+). By using X-ray photoelectron spectroscopy, UV-vis diffuse reflectance spectra and density functional theory, the fluorescence response mechanism was elucidated where Hg2+ could interact with CNQDs/CNNNs, causing a structural change in the nanocomposite, further affecting its bandgap structure, and finally leading to fluorescence quenching. The linear range for detecting Hg2+ was found to be 0.025-4.0 µmol L-1, with a detection limit of 7.82 nmol L-1. This strategy provided the advantages of a rapid response and a broad detection range, making it suitable for quantitative detection of Hg2+ in environmental water.

Near-infrared dye IRDye800CW-NHS coupled to Trastuzumab for near-infrared II fluorescence imaging in tumor xenograft models of HER-2-positive breast cancer.

Near-infrared II fluorescent probes targeting tumors for diagnostic purposes have received much attention in recent years. In this study, a fluorescent probe for the NIR-II was constructed by using IRDye800CW-NHS fluorescent dye with Trastuzumab, which was investigated for its ability to target HER-2-positive breast cancer in xenograft mice models. This probe was compared with Trastuzumab-ICG which was synthesized using a similar structure, ICG-NHS. The results demonstrated that the IRDye800CW-NHS had significantly stronger fluorescence in the NIR-I and NIR-II than ICG-NHS in the aqueous phase. And the different metabolic modes of IRDye800CW-NHS and ICG-NHS were revealed in bioimaging experiments. IRDye800CW-NHS was mainly metabolised by the kidneys, while ICG-NHS was mainly metabolised by the liver. After coupling with Trastuzumab, Trastuzumab-800CW (TMR = 5.35 ± 0.39) not only had a stronger tumor targeting ability than Trastuzumab-ICG (TMR = 4.42 ± 0.10) based on the calculated maximum tumor muscle ratio (TMR), but also had a comparatively lower hepatic uptake and faster metabolism. Histopathology analysis proved that both fluorescent probes were non-toxic to various organ tissues. These results reveal the excellent optical properties of IRDye800CW-NHS, and the great potential of coupling with antibodies to develop fluorescent probes that will hopefully be applied to intraoperative breast cancer navigation in humans.

A new ratiometric fluorescence nanosensor based on NaYF4:3%Er@NaYF4 upconversion nanoparticles for sensitive determination of Rose Bengal in water.

Rose Bengal (RB) is used as a sensitizer in ambient water due to its property of catalyzing the production of singlet oxygen (1O2). However, this property also brings phototoxicity and carcinogenicity. The NaYF4:3%Er@NaYF4 core-shell upconversion nanoparticles (UCNPs) with higher upconversion efficiency was synthesized to detect RB in ambient water. Due to fluorescence resonance energy transfer (FRET) between RB and UCNPs, the upconversion fluorescence at 538 nm emitted by UCNPs was quenched by the RB, while the emission at 566 nm of RB raised. In the best conditions, the ratiometric emission intensity F566/F538 was positively proportional to RB concentration and the linear range was 0.04-15.0 µg·mL-1 (R2 = 0.996). The detection limit (S/N = 3) of RB was 2.46 ng·mL-1. The recoveries ranged from 99.0% to 105.6% (relative standard deviation 0.97-3.24%, n = 3) in tap water and 100.3%-104.9% (relative standard deviation 0.66-1.94%, n = 3) in lake water. This proposed method exhibits lower detection limit and larger linear, which possesses practical application value to the detection of RB in water.

Trifolirhizin inhibits proliferation, migration and invasion in nasopharyngeal carcinoma cells via PI3K/Akt signaling pathway suppression.

Nasopharyngeal carcinoma (NPC) is a highly recurrent and metastatic malignant tumor affecting a large number of individuals in southern China. Traditional Chinese herbal medicine has been found to be a rich source of natural compounds with mild therapeutic effects and minimal side effects, making them increasingly popular for treating various diseases. Trifolirhizin, a natural flavonoid derived from leguminous plants, has gained significant attention for its therapeutic potential. In this study, we confirmed that trifolirhizin could effectively inhibit the proliferation, migration and invasion of nasopharyngeal carcinoma 6-10B and HK1 cells. Furthermore, our findings demonstrated that trifolirhizin achieves this by suppressing the PI3K/Akt signaling pathway. The findings of the present study provides a valuable perspective on the potential therapeutic applications of trifolirhizin for the treatment of nasopharyngeal carcinoma.

The Association of Perceived Neighbourhood Environment and Subjective Wellbeing in Migrant Older Adults: A Cross-Sectional Study Using Canonical Correlation Analysis.

Existing studies often focus on the impact of the neighbourhood environment on the subjective wellbeing (SWB) of the residents. Very few studies explore the impacts of the neighbourhood environment on migrant older adults. This study was conducted to investigate the correlations between perceived neighbourhood environment (PNE) and SWB among migrant older adults. A cross-sectional design was adopted. Data were collected from 470 migrant older adults in Dongguan, China. General characteristics, levels of SWB, and PNE were collected via a self-reported questionnaire. Canonical correlation analysis was performed to evaluate the relationship between PNE and SWB. These variables accounted for 44.1% and 53.0% of the variance, respectively. Neighbourhood relations, neighbourhood trust, and similar values in social cohesion made the most important contributions correlated with positive emotion and positive experience. A link between SWB and walkable neighbourhoods characterized by opportunities and facilities for physical activities with other people walking or exercising in their community, is positively associated with positive emotions. Our findings suggest that migrant older adults have a good walkable environment and social cohesion in neighbourhoods positively correlated with their subjective wellbeing. Therefore, the government should provide a more robust activity space for neighbourhoods and build an inclusive community for older adults.

The Subjective Well-Being of Elderly Migrants in Dongguan: The Role of Residential Environment.

To examine the association between community and individual-level residential environment in relation to subjective well-being (SWB) amongst 470 elderly migrants in China, this community-based survey was conducted. The manner and extent to which the SWB of these elderly migrants is influenced by their residential environment was the main area of focus. The Scale of Happiness of the Memorial University of Newfoundland was used to assess SWB. SWB was found to be associated significantly with environmental factors such as social cohesion, closeness to the nearest facility of recreation, the density of recreation facilities, financial facilities, and health facilities. The health facility density (B = 0.026, p < 0.001) and recreation facility density (B = 0.032, p < 0.001) had positive associations with SWB, while financial facility density (B = −0.035, p < 0.001) had a negative association. The primary determinants of SWB for elderly migrants ranged from individual to environmental factors. Through the enhancement of the accessibility to healthcare facilities in their new homes, in addition to promoting recreational activities and social services, the SWB amongst elderly migrants could be enhanced further.

Evaluation of a Gene-Environment Interaction of PON1 and Low-Level Nerve Agent Exposure with Gulf War Illness: A Prevalence Case-Control Study Drawn from the U.S. Military Health Survey's National Population Sample.

BACKGROUND: Consensus on the etiology of 1991 Gulf War illness (GWI) has been limited by lack of objective individual-level environmental exposure information and assumed recall bias. OBJECTIVES: We investigated a prestated hypothesis of the association of GWI with a gene-environment (GxE) interaction of the paraoxonase-1 (PON1) Q192R polymorphism and low-level nerve agent exposure. METHODS: A prevalence sample of 508 GWI cases and 508 nonpaired controls was drawn from the 8,020 participants in the U.S. Military Health Survey, a representative sample survey of military veterans who served during the Gulf War. The PON1 Q192R genotype was measured by real-time polymerase chain reaction (RT-PCR), and the serum Q and R isoenzyme activity levels were measured with PON1-specific substrates. Low-level nerve agent exposure was estimated by survey questions on having heard nerve agent alarms during deployment. RESULTS: The GxE interaction of the Q192R genotype and hearing alarms was strongly associated with GWI on both the multiplicative [prevalence odds ratio (POR) of the interaction=3.41; 95% confidence interval (CI): 1.20, 9.72] and additive (synergy index=4.71; 95% CI: 1.82, 12.19) scales, adjusted for measured confounders. The Q192R genotype and the alarms variable were independent (adjusted POR in the controls=1.18; 95% CI: 0.81, 1.73; p=0.35), and the associations of GWI with the number of R alleles and quartiles of Q isoenzyme were monotonic. The adjusted relative excess risk due to interaction (aRERI) was 7.69 (95% CI: 2.71, 19.13). Substituting Q isoenzyme activity for the genotype in the analyses corroborated the findings. Sensitivity analyses suggested that recall bias had forced the estimate of the GxE interaction toward the null and that unmeasured confounding is unlikely to account for the findings. We found a GxE interaction involving the Q-correlated PON1 diazoxonase activity and a weak possible GxE involving the Khamisiyah plume model, but none involving the PON1 R isoenzyme activity, arylesterase activity, paraoxonase activity, butyrylcholinesterase genotypes or enzyme activity, or pyridostigmine. DISCUSSION: Given gene-environment independence and monotonicity, the unconfounded aRERI>0 supports a mechanistic interaction. Together with the direct evidence of exposure to fallout from bombing of chemical weapon storage facilities and the extensive toxicologic evidence of biochemical protection from organophosphates by the Q isoenzyme, the findings provide strong evidence for an etiologic role of low-level nerve agent in GWI. https://doi.org/10.1289/EHP9009.

Patient preferences and attitudes towards first choice medical services in Shenzhen, China: a cross-sectional study.

OBJECTIVE: This study aimed to explore the characteristics of Shenzhen residents' preferences and influencing factors regarding their first choice of medical institution at various medical levels, and to understand their attitudes towards community health services. DESIGN: Cross-sectional survey. PARTICIPANTS: A total of 1612 participants at least 18 years of age were randomly sampled with stratification among 10 districts in Shenzhen. Data were gathered through a self-designed questionnaire. The effective questionnaire response rate was 93.05%. All patients participated in the study voluntarily, provided written informed consent and were able to complete the questionnaire. MAIN OUTCOME MEASURES: We measured and compared the participants' expected and actual preferences and influencing factors regarding their first choice of medical service at various medical levels. RESULTS: More than 50% of the participants preferred municipal and district hospitals as their first choice, and 27.5% chose medical institutions according to specific circumstances. Univariate analysis indicated that age, education, income, medical insurance, housing conditions and registered permanent residence were significantly associated with the actual and expected preferred first medical institution. The main factors influencing participants' actual and expected preferred medical institution differed. With the actual preferred first medical institution as the dependent variable, education, monthly income, medical technology, convenience and providers' service attitude and medical ethics were the main factors (χ2=212.63, p<0.001), whereas with the expected preferred first medical institution as the dependent variable, occupation, Shenzhen registered permanent residence, education and medical technology were the main factors (χ2=78.101, p<0.001). CONCLUSION: The main factors influencing participants' preferred medical institution and their actual first visit differed. Patients with high education or income or registered permanent residence preferred high-level medical institutions for the first visit.

A Novel Process to Recover Gypsum from Phosphogypsum.

In this study, we investigated a coarse phosphogypsum containing 49.63% SO3, 41.41% CaO, 10.68%, 4.47% SiO2, 1.28% P2O5, 0.11% F, CaSO4·2H2O purity of 80.65%, and whiteness of 27.68. Phosphogypsum contains calcium sulfate dehydrate as the main mineral, with small amounts of brushite, quartz, muscovite, and zoisite. Harmful elements, such as silicon, phosphorus, and fluorine, are mainly concentrated in the +0.15 mm and -0.025 mm fraction, which can be pre-selected and removed by the grading method to further increase the CaSO4·2H2O content. Gypsum was recovered using a direct flotation method, which included one roughing, one scavenging, and two cleaning operations, from -0.15 mm to +0.025 mm. The test results show that a gypsum concentrate with a CaSO4·2H2O purity of 98.94%, CaSO4·2H2O recovery of 80.02%, and whiteness of 37.05 was achieved. The main mineral in the gypsum concentrate was gypsum, and limited amounts of muscovite and zoisite entered the gypsum concentrate because of the mechanical entrainment of the flotation process.

Effects of Nano-α-Linolenic Acid and miR-146 on Mice with Viral Myocarditis.

Micro RNA-146 (miR-146) is involved in mediating many innate and adaptive immune and inflammatory responses in the body. It is associated with a variety of systemic inflammation or autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and type 2 diabetes. In recent years, microRNAs (miRNAs) and nanotechnology have become research hotspots in cardiovascular pathology. The close relationship between host miRNAs and coxsackie virus B3 has gradually been discovered by scientists, which may provide new directions for the treatment and prevention of viral myocarditis. At the same time, recent studies have also found that nano-α-linolenic acid and its metabolites can inhibit the production of inflammatory cytokines such as TNF-α and IL-17; At the same time, they also have anti-lipid peroxidation effects. Therefore, in order to further explore the role of miR-146 and nano-α-linolenic acid in the occurrence and development of viral myocarditis, in this study, a mouse model of viral myocarditis was used to establish a VMC mouse model using coxsackie virus B3. Intervention with different doses of nano-α-linolenic acid, the control group was injected with the same amount of sodium chloride buffer, and the changes in cardiac function and inflammation indexes were compared to evaluate the role in the pathogenesis of viral myocarditis. The results showed that this study suggested that serum miR-146 concentration in viral myocarditis mice is increased and is positively correlated with serum IL-17 and TNF-α concentrations. This suggest that miR-146 in the circulation may be involved in the pathogenesis of viral myocarditis through IL-17 and TNF-α, providing a theoretical basis for the role of miR-146 in viral myocarditis, but its specific mechanism of action needs to be further studied. At the same time, the research in this experiment showed that nano-α-linolenic acid significantly improves the survival rate of CVB3 infected mice and reduces myocardial damage. And with the increase of the dosage of nano-α-linolenic acid, the effect is more significant, showing a significant dose-effect relationship.

Factors influencing utilization of primary health care by elderly internal migrants in China: the role of social contacts.

BACKGROUND: Utilization of primary health care is an important aspect of elderly internal migrants' access to screening and preventive services in China. It has been evident that social contacts, such as community engagement, social mobilization, and the ability to communicate were related to health service delivery, but little has been done to explore the relationship between social contacts and utilization of primary health care for this group. This study aimed to explore the factors influencing utilization of primary health care from the perspective of social contacts among elderly internal migrants in China. METHODS: This was a cross-sectional study including 1544 elderly internal migrants in eight cities. Whether these indivdiuals had chosen to participate in the free health checkup organized in the previous year was adopted as an indicator of the utilization of primary health care. The number of local friends and amount of exercise time per day were measured as a proxy for social contacts. Multivariate binary logistic regression was used to investigate the association of social contacts with the likelihood of using primary health care. RESULTS: 55.6% of the respondents were men, and the mean age was 66.34 years (SD, 5.94). 88.6% had received an education of high school or below. 12.9% had no local friends. 5.2% did not exercise. Just 33.1% had participated in a free medical check-up. Social contacts, age, and medical insurance were associated with more use of primary health care among elderly internal migrants in China. CONCLUSION: The role of the community in promoting the use of primary health care should be expanded, such as creating community-based campaigns specifically targeting elderly internal migrants or designing social or sports activities tailored to increase the opportunity for contact between local elders and their internal migrant peers.

Co-expression analysis provides important module and pathways of human dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a heart disease that injured greatly to the people wordwide. Systemic co-expression analysis for this cancer is still limited, although massive clinic experiments and gene profiling analyses had been well performed previously. Here, using the public RNA-Seq data "GSE116250" and gene annotation of Ensembl database, we built the co-expression modules for DCM by Weighted Gene Co-Expression Network Analysis, and investigated the function enrichment and protein-protein interaction (PPI) network of co-expression genes of each module by Database for Annotation, Visualization, and Integrated Discovery and Search Tool for the Retrieval of Interacting Genes/Proteins database, respectively. First, 5,000 genes in the 37 samples were screened and 11 co-expression modules were conducted. The number of genes for each module ranged from 77 to 936, with a mean of 455. Second, interaction relationships of hub-genes between pairwise modules showed great differences, suggesting relatively high-scale independence of the modules. Third, functional enrichments of the co-expression modules exhibited great differences. We found that genes in module 3 were significantly enriched in the pathways of focal adhesion and ubiquitin-mediated proteolysis. This module was inferred as the key module involved in DCM. In addition, PPI analysis revealed that the genes HSP90AA1, CTNNB1, MAPK1, GART, and PPP2CA owned the largest number of adjacency genes, unveiling that they may function importantly during the occurrence of DCM. Focal adhesion and ubiquitin-mediated proteolysis play important roles in human DCM.

High Level of Lipoprotein(a) as Predictor for Recurrent Heart Failure in Patients with Chronic Heart Failure: a Cohort Study / Nível Alto de Lipoproteína (a) como Preditor de Insuficiência Cardíaca Recorrente em Pacientes com Insuficiência Cardíaca Crônica: um Estudo de Coorte

Abstract Background: Elevated plasma levels of Lipoprotein(a) [Lp(a)] are recognized as a significant risk factor for atherosclerotic vascular disease. However, there are limited data regarding association between Lp(a) and recurrent heart failure (HF) in patients with chronic HF caused by coronary heart disease (CHD). Objective: Elevated levels of Lp(a) might have a prognostic impact on recurrent HF in patients with chronic HF caused by CHD. Methods: A total of 309 patients with chronic HF caused by CHD were consecutively enrolled in this study. The patients were divided into 2 groups according to whether Lp(a) levels were above or below the median level for the entire cohort (20.6 mg/dL): the high Lp(a) group (n = 155) and the low Lp(a) group (n = 154). A 2-sided p < 0.05 was statistically considered significant. Results: During the median follow-up period of 186 days, 31 cases out of a total of 309 patients (10.03%) could not be reached during follow-up. A Kaplan-Meier analysis demonstrated that patients with higher Lp(a) levels had a higher incidence of recurrent HF than those with lower Lp(a) levels (log-rank < 0.0001). A multivariate Cox regression analysis revealed that Lp(a) levels were independently correlated with the incidence of recurrent HF after adjustment of potential confounders (hazard ratio: 2.720, 95 % confidence interval: 1.730-4.277, p < 0.0001). Conclusions: In Chinese patients with chronic HF caused by CHD, elevated levels of Lp(a) are independently associated with recurrent HF.

Resumo Fundamento: Níveis plasmáticos elevados de lipoproteína (a) [Lp(a)] são reconhecidos como um fator de risco significativo para doença vascular aterosclerótica. No entanto, existem dados limitados sobre a associação entre a Lp(a) e insuficiência cardíaca (IC) recorrente em pacientes com IC crônica causada por doença arterial coronariana (DAC). Objetivo: Níveis elevados de Lp(a) podem ter um impacto prognóstico na IC recorrente em pacientes com IC crônica por DAC. Métodos: Um total de 309 pacientes com IC crônica causada por DAC foram consecutivamente incluídos neste estudo. Os pacientes foram divididos em 2 grupos de acordo com os níveis de Lp(a), acima ou abaixo do nível mediano de toda a coorte (20,6 mg/dL): o grupo Lp(a) alto (n = 155) e o grupo Lp ( a) baixo (n = 154). Um p < 0,05 bicaudal foi considerado estatisticamente significativo. Resultados: Durante a mediana do período de seguimento de 186 dias, 31 casos de um total de 309 pacientes (10,03%) não puderam ser contatados durante o acompanhamento. A análise de Kaplan-Meier demonstrou que pacientes com níveis mais elevados de Lp(a) apresentavam maior incidência de IC recorrente do que aqueles com níveis mais baixos de Lp(a) (log-rank < 0,0001). Uma análise de regressão multivariada de Cox revelou que os níveis de Lp(a) foram independentemente correlacionados com a incidência de IC recorrente após ajuste de potenciais fatores de confusão (hazard ratio 2,720, intervalo de confiança de 95%: 1,730-4,277, p < 0,0001). Conclusões: Em pacientes chineses com IC crônica causada por DAC, níveis elevados de Lp(a) estão associados de forma independente à IC recorrente.

High Level of Lipoprotein(a) as Predictor for Recurrent Heart Failure in Patients with Chronic Heart Failure: a Cohort Study.

BACKGROUND: Elevated plasma levels of Lipoprotein(a) [Lp(a)] are recognized as a significant risk factor for atherosclerotic vascular disease. However, there are limited data regarding association between Lp(a) and recurrent heart failure (HF) in patients with chronic HF caused by coronary heart disease (CHD). OBJECTIVE: Elevated levels of Lp(a) might have a prognostic impact on recurrent HF in patients with chronic HF caused by CHD. METHODS: A total of 309 patients with chronic HF caused by CHD were consecutively enrolled in this study. The patients were divided into 2 groups according to whether Lp(a) levels were above or below the median level for the entire cohort (20.6 mg/dL): the high Lp(a) group (n = 155) and the low Lp(a) group (n = 154). A 2-sided p < 0.05 was statistically considered significant. RESULTS: During the median follow-up period of 186 days, 31 cases out of a total of 309 patients (10.03%) could not be reached during follow-up. A Kaplan-Meier analysis demonstrated that patients with higher Lp(a) levels had a higher incidence of recurrent HF than those with lower Lp(a) levels (log-rank < 0.0001). A multivariate Cox regression analysis revealed that Lp(a) levels were independently correlated with the incidence of recurrent HF after adjustment of potential confounders (hazard ratio: 2.720, 95 % confidence interval: 1.730-4.277, p < 0.0001). CONCLUSIONS: In Chinese patients with chronic HF caused by CHD, elevated levels of Lp(a) are independently associated with recurrent HF.

Identification of biologically active δ-lactone eicosanoids as paraoxonase substrates.

The mammalian paraoxonases (PONs 1, 2 and 3) are a family of esterases that are highly conserved within and between species. They exhibit antioxidant and anti-inflammatory activities. However, their physiological function(s) and native substrates are uncertain. Previous structure-activity relationship studies demonstrate that PONs have a high specificity for lipophilic lactones, suggesting that such compounds may be representative of native substrates. This report describes the ability of PONs to hydrolyze two bioactive δ-lactones derived from arachidonic acid, 5,6-dihydroxy-eicosatrienoic acid lactone (5,6-DHTL) and cyclo-epoxycyclopentenone (cyclo-EC). Both lactones were very efficiently hydrolyzed by purified PON3. PON1 efficiently hydrolyzed 5,6-DHTL, but with a specific activity about 15-fold lower than PON3. 5,6-DHTL was a poor substrate for PON2. Cyclo-EC was a poor substrate for PON1 and not hydrolyzed by PON2. Studies with the PON inhibitor EDTA and a serine esterase inhibitor indicated that the PONs are the main contributors to hydrolysis of the lactones in human and mouse liver homogenates. Studies with homogenates from PON3 knockout mouse livers indicated that >80% of the 5,6-DHTL and cyclo-EC lactonase activities were attributed to PON3. The findings provide further insight into the structural requirements for PONs substrates and support the hypothesis that PONs, particularly PON1 and PON3, evolved to hydrolyze and regulate a class of lactone lipid mediators derived from polyunsaturated fatty acids.

The cardioprotective effect of thymoquinone on ischemia-reperfusion injury in isolated rat heart via regulation of apoptosis and autophagy.

Thymoquinone (TQ), as the active constituents of black cumin (Nigella sativa) seed oil, has been reported to have potential protective effects on the cardiovascular system. This study aimed to investigate the effects and the underlying mechanisms of TQ on myocardial ischemia-reperfusion (I/R) injury in Langendorff-perfused rat hearts. Wister rat hearts were subjected to I/R and the experimental group were pretreated with TQ prior to I/R. Hemodynamic parameters, myocardial infarct size, cardiac marker enzymes, superoxide dismutase (SOD), malondialdehyde (MDA) content, and cardiomyocyte apoptosis were assayed. Compared with the untreated group, TQ preconditioning significantly improved cardiac function, reduced infarct size, decreased cardiac lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) levels, suppressed enedoxidative stress, and apoptosis. In addition, TQ treatment promoted autophagy, which was partially reversed by chloroquine (CQ), a kind of autophagy blocker. Our study suggests that TQ can protect heart against I/R injury, which is associated with anti-oxidative and anti-apoptotic effects through activation of autophagy.