Gender differences in the relationship between serum uric acid and the long-term prognosis in heart failure: a nationwide study.

BACKGROUND: Serum uric acid (SUA) is an important pathogenetic and prognostic factor for heart failure (HF). Gender differences are apparent in HF. Furthermore, gender differences also exist in the association between SUA and prognosis in various cardiovascular diseases. However, the gender difference for SUA in the prediction of long-term prognosis in HF is still ambiguous. METHODS: A total of 1593 HF patients (897 men, 696 women) from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 cycle were enrolled in our final analysis. Participants were categorized according to gender-specific SUA tertile. We assessed the association between SUA and long-term prognosis of HF patients, defined as all-cause mortality and cardiovascular mortality, in different genders via Kaplan-Meier curve analysis, Cox proportional hazard model, and Fine-Gray competing risk model. The restricted cubic spline (RCS) was performed to investigate the dose-response relationship between SUA and outcomes. RESULTS: Gender differences exist in demographic characteristics, clinical parameters, laboratory tests, and medication of HF patients. After a median follow-up of 127 months (95% CI 120-134 months), there were 853 all-cause deaths (493 events in men, 360 events in women) and 361 cardiovascular deaths (206 events in men, 155 events in women). Kaplan-Meier analysis showed that SUA had gender difference in the prediction of cardiovascular mortality (Log-rank p < 0.001, for male, Log-rank p = 0.150, for female), but not in all-cause mortality. Multivariate Cox regression analysis revealed that elevated SUA levels were associated with higher all-cause mortality and cardiovascular mortality in men (HR 1.11, 95% CI 1.05-1.18, p < 0.001, for all-cause death; HR 1.18, 95% CI 1.09-1.28, p < 0.001, for cardiovascular death), but not in women (HR 1.05, 95% CI 0.98-1.12, p = 0.186, for all-cause death; HR 1.01, 95% CI 0.91-1.12, p = 0.902, for cardiovascular death). Even using non-cardiovascular death as a competitive risk, adjusted Fine-Gray model also illustrated that SUA was an independent predictor of cardiovascular death in men (SHR 1.17, 95% CI 1.08-1.27, p < 0.001), but not in women (SHR 0.98, 95% CI 0.87 - 1.10, p = 0.690). CONCLUSIONS: Gender differences in the association between SUA and long-term prognosis of HF existed. SUA was an independent prognostic predictor for long-term outcomes of HF in men, but not in women.

Correlation between the triglyceride-glucose index and left ventricular global longitudinal strain in patients with chronic heart failure: a cross-sectional study.

BACKGROUND: Left ventricular global longitudinal strain (GLS) holds greater diagnostic and prognostic value than left ventricular ejection fraction (LVEF) in the heart failure (HF) patients. The triglyceride-glucose (TyG) index serves as a reliable surrogate for insulin resistance (IR) and is strongly associated with several adverse cardiovascular events. However, there remains a research gap concerning the correlation between the TyG index and GLS among patients with chronic heart failure (CHF). METHOD: 427 CHF patients were included in the final analysis. Patient demographic information, along with laboratory tests such as blood glucose, lipids profiles, and echocardiographic data were collected. The TyG index was calculated as Ln [fasting triglyceride (TG) (mg/dL) × fasting plasma glucose (FPG) (mg/dL)/2]. RESULTS: Among CHF patients, GLS was notably lower in the higher TyG index group compared to the lower TyG index group. Following adjustment for confounding factors, GLS demonstrated gradual decrease with increasing TyG index, regardless of the LVEF level and CHF classification. CONCLUSION: Elevated TyG index may be independently associated with more severe clinical left ventricular dysfunction in patients with CHF.

Establishment and Validation of a Mouse Bacterial Vaginosis Model.

BACKGROUND: Bacterial vaginosis (BV) is a common vaginal infection without a reliable animal model. To establish a novel mouse BV model, we evaluated multiple parameters of various identified bacteria-infected mice, including Staphylococcus aureus (SA), Escherichia coli (EC), Streptococcus agalactiae, ß-Hemolytic streptococcus, and Gardnerella vaginalis (GV). METHODS: Mature female KM mice were randomly allocated to a vehicle group (group A, without any treatment) and experimental groups. After vaginal secretions were harvested, experimental groups were divided into phosphate buffer solution group (PBS, group B), control group including SA, and EC with a 1:1 ratio (group C), SA, EC, and Streptococcus agalactiae with a 1:2:1 ratio group (group D), SA, EC, and ß-Hemolytic streptococcus with a 1:2:1 ratio group (group E), and GV group (group F). The vaginal secretions of experimental mice were collected by flushing with 100 mL sterile PBS on days 2, 4, and 6. Vaginal secretions were examined by Gram staining, sialidase assay, ammonia test, and pH value measurement. IL-6 and IL-10 levels in mouse serum were detected by enzyme-linked immunosorbent assay. Hematoxylineosin staining and mouse cervicovaginal tissue histopathological scores were observed. The diagnostic test results were analyzed by logistic regression analysis and receiver operating characteristic curves. The Shapiro-Wilk analysis of variance, or rank-sum test, was used for normal distribution analysis. Pearson's correlation and chi-squared test determined the correlation and comparison data expressed as a percentage or frequency. RESULTS: There was less severe vaginal morphology in GV-infected mice compared to other bacteria-infected mice. The sialidase assay, the ammonia test, and the pH values of vaginal secretions showed significant differences between GV-infected and uninfected mice. Serum IL-6 and IL-10 levels and vaginal histological scoring increased in other bacteria-infected mice, but GV-infected mice showed only a mildly increasing trend of IL-10 levels and vaginal histological scoring compared to control mice. CONCLUSIONS: GV-infected mice showed clinical features similar to human BV infection, including vaginal anatomical and pathological indices, and biochemical and immune parameters. Serum IL-10 level has potential for use in BV diagnosis.

Precision Therapy of Recurrent Breast Cancer through Targeting Different Malignant Tumor Cells with a HER2/CD44-Targeted Hydrogel Nanobot.

Heterogeneity and drug resistance of tumor cells are the leading causes of incurability and poor survival for patients with recurrent breast cancer. In order to accurately deliver the biological anticancer drugs to different subtypes of malignant tumor cells for omnidirectional targeted treatment of recurrent breast cancer, a distinct design is demonstrated by embedding liposome-based nanocomplexes containing pro-apoptotic peptide and survivin siRNA drugs (LPR) into Herceptin/hyaluronic acid cross-linked nanohydrogels (Herceptin-HA) to fabricate a HER2/CD44-targeted hydrogel nanobot (named as ALPR). ALPR delivered cargoes to the cells overexpressing CD44 and HER2, followed by Herceptin-HA biodegradation, subsequently, the exposed lipid component containing DOPE fused with the endosomal membrane and released peptide and siRNA into the cytoplasm. These experiments indicated that ALPR can specifically deliver Herceptin, peptide, and siRNA drugs to HER2-positive SKBR-3, triple-negative MDA-MB-231, and HER2-negative drug-resistant MCF-7 human breast cancer cells. ALPR completely inhibited the growth of heterogeneous breast tumors via multichannel synergistic effects: disrupting mitochondria, downregulating the survivin gene, and blocking HER2 receptors on the surface of HER2-positive cells. The present design overcomes the chemical drug resistance and opens a feasible route for the combinative treatment of recurrent breast cancer, even other solid tumors, utilizing different kinds of biological drugs.

Deficient Chaperone-Mediated Autophagy Promotes Inflammation and Atherosclerosis.

RATIONALE: The NLRP3 (NLR [NOD-like receptor] family, pyrin domain containing 3) inflammasome is an important driver of atherosclerosis. Our previous study shows that chaperone-mediated autophagy (CMA), one of the main lysosomal degradative process, has a regulatory role in lipid metabolism of macrophages. However, whether the NLRP3 inflammasome is regulated by CMA, and the role of CMA in atherosclerosis remains unclear. OBJECTIVE: To determine the role of CMA in the regulation of NLRP3 inflammasome and atherosclerosis. METHODS AND RESULTS: The expression of CMA marker, LAMP-2A (lysosome-associated membrane protein type 2A), was first analyzed in ApoE-/- mouse aortas and human coronary atherosclerotic plaques, and a significant downregulation of LAMP-2A in advanced atherosclerosis in both mice and humans was observed. To selectively block CMA, we generated macrophage-specific conditional LAMP-2A knockout mouse strains in C57BL/6 mice and ApoE-/- mice. Deletion of macrophage LAMP-2A accelerated atherosclerotic lesion formation in the aortic root and the whole aorta in ApoE-/- mice. Mechanistically, LAMP-2A deficiency promoted NLRP3 inflammasome activation and subsequent release of mature IL (interleukin)-1ß in macrophages and atherosclerotic plaques. Furthermore, gain-of-function studies verified that restoration of LAMP-2A levels in LAMP-2A-deficient macrophages greatly attenuated NLRP3 inflammasome activation. Importantly, we identified the NLRP3 protein as a CMA substrate and demonstrated that LAMP-2A deficiency did not affect the NLRP3 mRNA levels but hindered degradation of the NLRP3 protein through CMA pathway. CONCLUSIONS: CMA function becomes impaired during the progression of atherosclerosis, which increases NLRP3 inflammasome activation and secretion of IL-1ß, promoting vascular inflammation and atherosclerosis progression. Our study unveils a new mechanism by which NLRP3 inflammasome is regulated in macrophages and atherosclerosis, thus providing a new insight into the role of autophagy-lysosomal pathway in atherosclerosis. Pharmacological activation of CMA may provide a novel therapeutic strategy for atherosclerosis and other NLRP3 inflammasome/IL-1ß-driven diseases.

Ethnobotanical survey of antifertility medicinal plants in Dali District, Yunnan Province, China.

In recent years, contraceptive medication has been widely used for birth control. It is worth noting that contraceptive medication from botanical source has great potential for clinical use. Yunnan is the province with the most species of plants in China and is known as the "plant kingdom". This study aims to archive herbal remedies traditionally used as antifertility remedies in Dali District, Yunnan Province, P. R. China. The survey was conducted from February 2011 to September 2016 in the population distributed in Dali and the surrounding counties. The data were collected from three groups of practitioners within the study area: therapists using traditional medicines (n = 104), aboriginal families (n = 37), and herbalists in commercial stalls (n = 12), and a total number of 117 plant species were recorded. Among the 117 plant species, 104 of which have been authenticated by a plant taxonomist from the Dali Herbarium. These plants were classified into 98 genera and 54 families, including Leguminosae (12 species), Liliaceae (7 species), Cucurbitaceae, Rosaceae and Rutaceae (5 species, respectively), Malvaceae, Compositae and Euphorbiaceae (4 species, respectively). Our data provides an in-depth delineation of the contraceptive plants used in Dali, which serve as valuable information for the practitioners of traditional Chinese medicine in contraceptive use. In addition, these data also hint that plants from different genus contain contraceptive components, which should be avoided by pregnant women. Future studies are required to identify the active contraceptive components, assess the toxicology, and elucidate the pharmacological mechanism of action.

Structure of benzothiadiazine at zwitterionic phospholipid cell membranes.

The use of drugs derived from benzothiadiazine, which is a bicyclic heterocyclic benzene derivative, has become a widespread treatment for diseases such as hypertension (treated with diuretics such as bendroflumethiazide or chlorothiazide), low blood sugar (treated with non-diuretic diazoxide), or the human immunodeficiency virus, among others. In this work, we have investigated the interactions of benzothiadiazine with the basic components of cell membranes and solvents, such as phospholipids, cholesterol, ions, and water. The analysis of the mutual microscopic interactions is of central importance to elucidate the local structure of benzothiadiazine as well as the mechanisms responsible for the access of benzothiadiazine to the interior of the cell. We have performed molecular dynamics simulations of benzothiadiazine embedded in three different model zwitterionic bilayer membranes made by dimyristoylphosphatidylcholine, dioleoylphosphatidylcholine, 1,2-dioleoyl-sn-glycero-3-phosphoserine, and cholesterol inside aqueous sodium-chloride solution in order to systematically examine microscopic interactions of benzothiadiazine with the cell membrane at liquid-crystalline phase conditions. From data obtained through radial distribution functions, hydrogen-bonding lengths, and potentials of mean force based on reversible work calculations, we have observed that benzothiadiazine has a strong affinity to stay at the cell membrane interface although it can be fully solvated by water in short periods of time. Furthermore, benzothiadiazine is able to bind lipids and cholesterol chains by means of single and double hydrogen-bonds of different characteristic lengths.

Application of SF-Cube 2.0 Technology in Platelet Count in Patients with EDTA-Dependent Pseudothrombocytopenia.

BACKGROUND: To explore the application of SF-Cube 2.0 technology in platelet count in patients with EDTA-dependent pseudothrombocytopenia (EDTA-PTCP). METHODS: Twenty-two out-patients and in-patients with EDTA-PTCP in our hospital were selected from February 1, 2020, to August 31, 2020. With the permission of each patient, blood samples of EDTA and sodium citrate anticoagulant tubes were collected. EDTA anticoagulant samples were tested by using the "complete blood cell count and white blood cell differential count"(CD) mode, and "complete blood cell count, white blood cell differential count, and reticulocyte count" (CDR) mode of the Mindray BC-6800Plus automated hematology analyzer, and the platelet counts were compared with the sample of sodium citrate anticoagulant from this patient. RESULTS: As SF-Cube 2.0 technology (implemented by using the CDR mode of the Mindray BC-6800Plus) was used, the platelet count of EDTA-PTCP sample was consistent with that of sodium citrate anticoagulant, which was significantly higher than that of CD detection mode. CONCLUSIONS: SF-Cube 2.0 technology can effectively correct the platelet counts in people with known or suspected EDTA-PTCP.

Microscopic Interactions of Melatonin, Serotonin and Tryptophan with Zwitterionic Phospholipid Membranes.

The interactions at the atomic level between small molecules and the main components of cellular plasma membranes are crucial for elucidating the mechanisms allowing for the entrance of such small species inside the cell. We have performed molecular dynamics and metadynamics simulations of tryptophan, serotonin, and melatonin at the interface of zwitterionic phospholipid bilayers. In this work, we will review recent computer simulation developments and report microscopic properties, such as the area per lipid and thickness of the membranes, atomic radial distribution functions, angular orientations, and free energy landscapes of small molecule binding to the membrane. Cholesterol affects the behaviour of the small molecules, which are mainly buried in the interfacial regions. We have observed a competition between the binding of small molecules to phospholipids and cholesterol through lipidic hydrogen-bonds. Free energy barriers that are associated to translational and orientational changes of melatonin have been found to be between 10-20 kJ/mol for distances of 1 nm between melatonin and the center of the membrane. Corresponding barriers for tryptophan and serotonin that are obtained from reversible work methods are of the order of 10 kJ/mol and reveal strong hydrogen bonding between such species and specific phospholipid sites. The diffusion of tryptophan and melatonin is of the order of 10-7 cm2/s for the cholesterol-free and cholesterol-rich setups.

Case report: Mycobacterium monacense isolated from the blood culture of a patient with pulmonary infection.

BACKGROUND: The poorly known mycobacterial species Mycobacterium monacense is a rapidly growing non-tuberculous mycobacterium that was first described in 2006 (Reischl et al., Int J Syst Evol Microbiol 56:2575-8, 2006); it has been reported that its isolation is usually associated with skin and lung infections, especially in immunosuppressed patients (Hogardt et al., Jpn J Infect Dis 61:77-8, 2008; Taieb et al., J Hand Surg Am 33:94-6, 2008; Therese et al., Lung India 28:124-6, 2011; Shojaei et al., Ann Lab Med 32:87-90, 2012; Romero et al., New Microbes New Infect 10:112-5, 2016 ). The clinical significance of Mycobacterium monacense is not yet fully understood. Here, we report the first isolation of Mycobacterium monacense from the blood culture of a patient in China with severe pneumonia. CASE PRESENTATION: On June 26, 2018, a 38-year-old man was admitted to the intensive care unit with breathing difficulty. One day prior, he was discovered with his face immersed in a small pond (non-chlorinated water) and with limb convulsions. He had undergone craniocerebral surgery after trauma 5 years earlier, which left him with epilepsy as a sequela. Bilateral diffuse ground-glass opacity was found in the lungs on chest X ray and chest CT image at admission. The result of the HIV serology test of the patient was negative. The patient was diagnosed with severe pneumonia. Drug-susceptible Klebsiella pneumoniae and Candida glabrata were isolated in the BALF, and yellow-pigmented colonies were isolated from blood cultures of the patient. The strain isolated from blood was identified by 16S rDNA sequencing as Mycobacteria monacense, which is a rapidly growing mycobacterium (RGM). The patient was treated with a combination of cefoperazone sulbactam, linezolid and voriconazole for 10 days, and the symptoms improved. During the one-year follow-up time, the patient did not relapse. CONCLUSIONS: We report the first case of M. monacense isolated from blood cultures in a patient with severe pneumonia, which provided evidence that the environmental microorganism possessed pathogenic characteristics.

Smooth muscle-specific Gsα deletion exaggerates angiotensin II-induced abdominal aortic aneurysm formation in mice in vivo.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease without an effective pharmaceutical treatment. Genetic studies have proved the involvement of smooth muscle phenotype switch in the development of AAA. The alpha subunit of the heterotrimeric G stimulatory protein (Gsα) mediates receptor-stimulated production of cyclic adenosine monophosphate (cAMP). However, the role of smooth muscle Gsα in AAA formation remains unknown. APPROACH AND RESULTS: In this study, mice with knockout of smooth muscle-specific Gsα (GsαSMKO) were generated by cross-breeding Gsαflox/flox mice with SM22-CreERT2 transgenic mice, induced in adult mice by tamoxifen treatment. Gsα deficiency induced a smooth muscle phenotype switch from a contractile to a synthetic state. Mechanically, Gsα deletion reduced cAMP level and increased the level of human antigen R (HuR), which binds with the adenylate uridylate-rich elements of the 3' untranslated region of Krüppel-like factor 4 (KLF4) mRNA, thereby increasing the stability of KLF4. Moreover, genetic knockdown of HuR or KLF4 rescued the phenotype switch in Gsα-deficient smooth muscle cells. Furthermore, with acute infusion of angiotensin II, the incidence of AAA was markedly higher in ApoE-/-/GsαSMKO than ApoE-/-/Gsαflox/flox mice and induced increased elastic lamina degradation and aortic expansion. Finally, the levels of Gsα and SM α-actin were significantly lower while those of HuR and KLF4 were higher in human AAA samples than adjacent nonaneurysmal aortic sections. CONCLUSIONS: Gsα may play a protective role in AAA formation by regulating the smooth muscle phenotype switch and could be a potential therapeutic target for AAA disease.

Ginsenoside Rb1 ameliorates CKD-associated vascular calcification by inhibiting the Wnt/ß-catenin pathway.

Vascular calcification (VC) is a pathological process underpinning major cardiovascular conditions and has attracted public attention due to its high morbidity and mortality. Chronic kidney disease (CKD) is a common disease related to VC. Ginsenoside Rb1 (Rb1) has been reported to protect the cardiovascular system against vascular diseases, yet its role in VC and the underlying mechanisms remain unclear. In this study, we established a CKD-associated VC rat model and a ß-glycerophosphate (ß-GP)-induced vascular smooth muscle cell (VSMC) calcification model to investigate the effects of Rb1 on VC. Our results demonstrated that Rb1 ameliorated calcium deposition and VSMC osteogenic transdifferentiation both in vivo and in vitro. Rb1 treatment inhibited the Wnt/ß-catenin pathway by activating peroxisome proliferator-activated receptor-γ (PPAR-γ), and confocal microscopy was used to show that Rb1 inhibited ß-catenin nuclear translocation in VSMCs. Furthermore, SKL2001, an agonist of the Wnt/ß-catenin pathway, compromised the vascular protective effect of Rb1. GW9662, a PPAR-γ antagonist, reversed Rb1's inhibitory effect on ß-catenin. These results indicate that Rb1 exerted anticalcific properties through PPAR-γ/Wnt/ß-catenin axis, which provides new insights into the potential theraputics of VC.

A comparative study of the effects of palm olein, cocoa butter and extra virgin olive oil on lipid profile, including low-density lipoprotein subfractions in young healthy Chinese people.

The aim of this study is to investigate the effects of palm olein (POL), cocoa butter (CB) and extra virgin olive oil (EVOO) on the lipid profile and low-density lipoprotein subfractions in a young, healthy Chinese population. After screening, 72 subjects were randomly assigned to three groups, and an 18-week randomized crossover trial was conducted. The first phase was a 2-week run-in period, followed by three phases of the 4-week experimental periods with a 2-week washout period between experimental periods. Three groups of subjects alternately consumed a Chinese diet enriched with the different test oils. The various indices of subjects were collected before and after each experimental period. Sixty-seven subjects completed the study, and there were no significant differences in conventional indices amongst the three groups at the beginning of the three experimental periods (p > .05). Each test oil accounted for approximately 40% of total fat intake and approximately 11.3% of the total energy supply. After controlling for dietary interventions, only the serum triglyceride level of the POL-Diet was significantly lower than that of the EVOO-Diet (p = .034), and most indices did not significantly differ amongst the three test oil diets (p > .05). POL, CB and EVOO have almost identical effects on serum lipids.

Ginsenoside Rb1 enhances atherosclerotic plaque stability by skewing macrophages to the M2 phenotype.

Atherosclerosis (AS) is characterized as progressive arterial plaque, which is easy to rupture under low stability. Macrophage polarization and inflammation response plays an important role in regulating plaque stability. Ginsenoside Rb1 (Rb1), one of the main active principles of Panax Ginseng, has been found powerful potential in alleviating inflammatory response. However, whether Rb1 could exert protective effects on AS plaque stability remains unclear. This study investigated the role of Rb1 on macrophage polarization and atherosclerotic plaque stability using primary peritoneal macrophages isolated from C57BL/6 mice and AS model in ApoE-/- mice. In vitro, Rb1 treatment promoted the expression of arginase-I (Arg-I) and macrophage mannose receptor (CD206), two classic M2 macrophages markers, while the expression of iNOS (M1 macrophages) was decreased. Rb1 increased interleukin-4 (IL-4) and interleukin-13 (IL-13) secretion in supernatant and promoted STAT6 phosphorylation. IL-4 and/or IL-13 neutralizing antibodies and leflunomide, a STAT6 inhibitor attenuated the up-regulation of M2 markers induced by Rb1. In vivo, the administration of Rb1 promoted atherosclerotic lesion stability, accompanied by increased M2 macrophage phenotype and reduced MMP-9 staining. These data suggested that Rb1 enhanced atherosclerotic plaque stability through promoting anti-inflammatory M2 macrophage polarization, which is achieved partly by increasing the production of IL-4 and/or IL-13 and STAT6 phosphorylation. Our study provides new evidence for possibility of Rb1 in prevention and treatment of atherosclerosis.

Contribution of TLR4 signaling in intermittent hypoxia-mediated atherosclerosis progression.

BACKGROUND: Intermittent hypoxia (IH), a typical character of obstructive sleep apnea (OSA), is related to atherogenesis. However, the role of IH on atherosclerosis (AS) progression and the mechanisms involved remains poorly understood. METHODS: In the present study, high-fat fed ApoE-/- mice were treated with recombinant shRNA-TLR4 lentivirus and exposed to IH. Atherosclerotic lesions on the en face aorta and cross-sections of aortic root were examined by Oil-Red O staining. The content of lipids and collagen of aortic root plaques were detected by Oil-Red O staining and Sirius red staining, respectively. The TLR4, NF-κB p65, α-SMA and MOMA-2 expression in aorta and IL-6 and TNF-α expression in the mice serum were also detected. RESULTS: Compared with the Sham group, the IH treated group further increased atherosclerotic plaque loads and plaque vulnerability in the aortic sinus. Along with increased TLR4 expression, enhanced NF-κB activation, inflammatory activity and aggravated dyslipidemia were observed in the IH treated group. TLR4 interference partly inhibited IH-mediated AS progression with decreased inflammation and improved cholesterol levels. Similarly, in endothelial cells, hypoxia/reoxygenation exposure has been shown to promote TLR4 expression and activation of proinflammatory TLR4/NF-κB signaling, while TLR4 interference inhibited these effects. CONCLUSIONS: We found that the IH accelerated growth and vulnerability of atherosclerotic plaque, which probably acted by triggering the activation of proinflammatory TLR4/NF-κB signaling. These findings may suggest that IH is a risk factor for vulnerable plaque and provide a new insight into the treatment of OSA-induced AS progression.

Effects of cholesterol on the binding of the precursor neurotransmitter tryptophan to zwitterionic membranes.

The characterization of the microscopical forces between the essential α-amino-acid tryptophan, precursor of the neurotransmitter serotonin and of the hormone melatonin, and the basic components of cell membranes and their environments (phospholipids, cholesterol, ionic species, and water) is of central importance to elucidate their local structure and dynamics as well as the mechanisms responsible for the access of tryptophan to the interior of the cell. We have performed nanosecond molecular dynamics simulations of tryptophan embedded in model zwitterionic bilayer membranes made by di-palmitoyl-phosphatidyl-choline and cholesterol inside aqueous sodium-chloride solution in order to systematically examine tryptophan-lipid, tryptophan-cholesterol, and tryptophan-water interactions under liquid-crystalline phase conditions. Microscopic properties such as the area per lipid, lipid thickness, radial distribution functions, hydrogen-bonding lengths, atomic spectral densities, and self-diffusion coefficients have been evaluated. Our results show that the presence of tryptophan significantly affects the structure and dynamics of the membrane. Tryptophan spends long periods of time at the water-membrane interface, and it plays a central role by bridging a few lipids and cholesterol chains by means of hydrogen-bonds. The computed spectral densities, in excellent agreement with experimental infrared and Raman data, revealed the participation of each atomic site of tryptophan to the complete spectrum of the molecule. Tryptophan self-diffusion coefficients have been found to be in between 10-7 and 10-6 cm2/s and strongly depending of the concentration of cholesterol in the system.

Retinoic acid regulates endometriotic stromal cell growth through upregulation of Beclin1.

PURPOSE: To elucidate the role of retinoic acid (RA) in autophagy-mediated endometriosis. METHODS: The mRNA and protein expressions of autophagy markers were examined in Ishikawa cells and endometriotic stromal cells (ESCs) after RA treatment. Beclin1 expression was specifically analyzed in clinical samples of endometriosis. The effect of Beclin1 knockdown on ESC growth was assessed, and the effect of autophagy inhibition on the sensitivity of endometriotic cells to RA was analyzed. RESULTS: RA treatment enhanced the autophagy in ESCs, and Beclin1 expression showed a negative correlation with the clinical stage of endometriosis. Beclin1 knockdown enhanced ESC growth, whereas RA treatment reversed this effect. Furthermore, inhibition of autophagy by chloroquine (CQ) and Beclin1 knockdown did not show any positive effect on the sensitivity of endometriotic cells to RA. CONCLUSIONS: RA treatment induces autophagy and Beclin1 may play an important role in endometriosis progression.

[Correlation of serum low density lipoprotein subfractions with routine lipid profile and physical indices in medical students from a university in 2016].

OBJECTIVE: To investigate the correlation among the serum low density lipoprotein subfractions, lipoprotein a and other routine indices. METHODS: Medical students who didn 't experience cardiovascular events were recruited at a university in Nanjing City, their physical indicators were measured( including height, weight, waist circumference and hip circumference) and fasting blood was collected to detect the seven items of serum lipid. Lipoprint system was used to detect low density lipoprotein subfractions, the correlation among the indices was analyzed ultimately. RESULTS: A total of 84 students( 40 male and 44 female) at the age of 20-29 were enrolled in the study. Levels of body mass index, waist-to-hip ratio, very low density lipoprotein, small dense low density lipoprotein in male were significantly higher than those in female, while levels ofhigh density lipoprotein, apolipoprotein A1, intermediate density lipoprotein and mean low density lipoprotein size in male were significantly lower than those in female( P < 0. 05). In this population, the abnormal rate of lipoprotein a reached 27. 4% and was only significantly positively correlated with high density lipoprotein( r = 0. 265, P = 0. 015), and the mean low density lipoprotein size was significantly negatively correlated with waist-to-hip ratio, triglyceride and small dense low density lipoprotein etc. ( P < 0. 05). CONCLUSION: Male medical students have more risk factors of angiocardiopathy than young women, and the abnormal rate of serum lipoprotein a in medical students is higher.

Leaching of metals from cement under simulated environmental conditions.

Leaching of metals from cement under various environmental conditions was measured to evaluate their environmental safety. A cement product containing clinker, which was produced from cement kiln co-processing of hazardous wastes, was solidified and leaching of metals was characterized using the 8-period test. Concentrations and speciation of metals in cements were determined. Effects of ambient environment and particle size on leachability of metals and mineralogical phases of cement mortars were evaluated by use of XRD and SEM. Results indicated that metals in cements were leachable in various media in descending order of: sea water, groundwater and acid rain. Cr, Ni, As, Co and V were leached by simulated sea water, while Cu, Cd, Pb, Zn, Mn, Sb and Tl were not leached in simulated sea water, groundwater or acid rain. When exposed to simulated acid rain or groundwater, amounts of Cr, Ni, As and V leached was inversely proportional to particle size of cement mortar. According to the one-dimensional diffusion equation, Cr was most leachable and the cumulative leached mass was predicted to be 9.6 mg kg(-1) after 20 years. Results of this study are useful in predicting releases of metals from cement products containing ash and clinkers cement kiln co-processing of hazardous wastes, so that they can be safely applied in the environment.

[Effects of diets with different n-6/n-3 fatty acids on cardiovascular risk factors in mice fed high-fat diets].

UNLABELLED: To investigate effects of diets with different fatty acid composition on serum lipid profiles, inflammation, oxidative stress and endothelial function in mice fed high-fat diets. METHODS: Male KM mice were randomly divided into five groups and were fed normal control diet, high-fat lard diet, high-fat diets with n-6/n-3 polyunsaturated fatty acid (PUFA) ratios of 1:1, 5:1 nd 2:1 for fiv weeks, respectively. The levels of serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C ) iterlekin-6 (IL-6), alonildehyde (MDA), hypersensitive C-reactive protein (hs-CRP), tumor ncrosis factor alpha (TNF-alpha), lipid lphaproxide (LPO), 8-iso postaglandin F2aalpha (8-iso-PGlphaF2u), oxidialphaed low-density lipoprotein (ox-LDL), free faty acid (FFA), E-selectin (ES) and von Willebrand factor (vWF) were measured. RESULTS: The levels of serum LDL-C and non-HDL-C in the lard group were significantly higher than those in the other groups (P < 0.05). Th e ard group had. significntly higher serum TG and TC concentrations compared to 1:1 and 5: groups P <0. 05). The evels of serum FFA in 20:1 group wre significantly higher than those in 1:1 and 5:1 groups P < 0.05). Co mpred with the lard and 20:1 groups,the 1:1 and 5:1 groups displayed lower levels of inflammatory cytokines, oxidative stress and ES. The 5:1 group sgnificantly decreased the level of serum vWF compared to lard and 20:1 groups P < 0.05). CONCLUSION: diet with low n-6/n-3 PUFA ratio could improve lipid metabolism, inflammation, oxidative stress and endothelial function compared to high-fat diets with lard and higher n-6/n-3 PUFA ratio. The diet with low n-6/n-3 PUFA ratio can improve cardiovascular disease risk factors to prevent cardiovascular disease.