Investigation of Zinc on hemorheological parameters in a rat model of diabetes.

Diabetes mellitus (DM) is a complex, chronic metabolic disorder characterized by impaired regulation of blood glucose levels. Zinc (Zn) is an essential trace elements that plays a role in various physiological processes within the body, including those related to diabetes. The current study was investigated the effect of Zn supplementation on hemorheological parameters in a rat model of DM. After induction of DM, 32 male Wistar albino rats were divided into four groups: control, Zn, DM, and Zn+DM. Whole blood viscosity (WBV) was determined by using digital cone and plate viscometer and plasma viscosity (PV) was determined by a Coulter Harkness capillary viscometer. The rats in the DM Group showed a decrease in both Zn levels and body weight, as well as an increase in glucose levels when compared to the control group. Diabetic rats supplemented with Zn displayed lower blood glucose levels and higher concentrations of Zn compared to the DM Group. The higher PV and lower hematocrit level were measured in DM Group than control group and lower PV, higher hematocrit level were measured in Zn+DM group than DM Group. The WBV was measured at four different shear rates (57.6-115.2 - 172.8-230.4 s -1). A statistically significant increase was observed in the DM group compared to the control group. Additionally, a statistically significant decrease was observed in the Zn+DM Group compared to the DM Group at a shear rate of 230.4 s-1. Erythrocyte rigidity index (Tk) and oxygen delivery index (ODI) were computed under conditions of high shear rate. The rats in the DM group exhibited a reduction in ODI and an elevation in Tk in comparison to the control group. Conversely, the diabetic rats supplemented with Zn exhibited decreased Tk and increased ODI compared to the DM Group. Zn supplementation seems to have a potential beneficial effect for protecting adverse affect of diabetes on hemorheogical parameters and for maintaining vascular health.

Effects of Low-Dose Aspirin Combined with Vitamin E on the Incidence of Intrauterine Growth Restriction and Hemorheological Indexes of Pregnant Women in Patients with Gestational Hypertension.

OBJECTIVE: To investigate the effect of low-dose aspirin combined with vitamin E on the incidence of intrauterine growth restriction and hemorheological indexes of pregnant women in patients with gestational hypertension. METHOD: 134 elderly patients with chronic urticaria treated in our hospital from November 2017 to November 2020 were studied. According to the treatment methods, they were randomly divided into observation and control groups. There were 67 patients in the observation group, aged 20-37 years, with an average of (25.7 ± 2.75) years. There were 67 patients in the control group, aged 21-35 years, with an average of (26.3 ± 3.17) years. No significant difference was observed between the two groups (P > 0.05). RESULTS: The number of cases with postpartum hemorrhage and intrauterine growth restriction in the observation group was less than that in the control group. The total incidence rate was lower than that in the control group. There were significant differences in the above results (P < 0.05). The number of patients with preterm birth in the observation group was less than that in the control group, but there was no significant difference in the results (P > 0.05). The head circumference, abdominal circumference, biparietal diameter, and femoral length diameter in the control and observation groups increased significantly after treatment (P < 0.05). Compared with the control group, the head circumference, abdominal circumference, biparietal diameter, and femoral diameter in the observation group increased more after treatment, and the results were statistically poor (P < 0.05). The systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the control and observation groups decreased significantly after treatment, and the results were statistically different (P < 0.05). Compared with the control group, the systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the observation group decreased more after treatment. The results were statistically different (P < 0.05). The plasma viscosity levels, whole blood high shear viscosity, and whole blood low shear viscosity in the control and observation groups decreased significantly after treatment, and the results were statistically different (P < 0.05). Compared with the control group, plasma viscosity levels, whole blood high shear viscosity, and whole blood low shear viscosity in the observation group decreased more after treatment, and the results were statistically different (P < 0.05). The control and observation groups' fetal systolic/diastolic pressure and pulsatile index decreased significantly after treatment, and the results were statistically different (P < 0.05). Compared with the control group, the fetal systolic/diastolic blood pressure and pulsatile index in the observation group decreased more after treatment, and the results were statistically poor (P < 0.05). CONCLUSION: Low-dose aspirin combined with vitamin E is effective in treating intrauterine growth restriction in patients with gestational hypertension. It can effectively control the blood pressure and blood flow of patients and newborns and improve pregnancy outcomes without increasing the incidence of adverse reactions. It is worthy of clinical promotion.

Screening of blood-activating active components from Curcuma wenyujin Y.H. Chen et C. Ling rhizome based on spectrum-effect relationship analysis and network pharmacology.

Curcuma wenyujin Y.H. Chen et C. Ling rhizome (also called EZhu in China) has long been used as plant medicine for its traditional effect on promoting blood circulation and remove blood stasis. However, the active components of EZhu are still unclear at present. This research is managed to investigate the pharmacodynamics material basis on removing blood stasis of EZhu by exploring the spectrum-effect relationship between UPLC-Q/TOF-MS fingerprints and pharmacologic actions. Hemorheology and related functional parameters were detected to evaluate the pharmacologic actions of EZhu. Relative content Changes of components in rat plasma were detected by UPLC-Q/TOF-MS. A compound-target-pathway network was built to predict the pharmacological activity of components in plasma. Then, bivariate correlation analysis (BCA) was used to explore the correlation degree between components in plasma and pharmacologic actions of EZhu. In UPLC-Q/TOF-MS fingerprints of rat plasma, 10 prototype components were identified. BCA results show that 8 components were concerned with the pharmacological activity for treating blood stasis syndrome (BSS) in varying degrees (R > 0.5, P < 0.05). Among them, zedoarofuran and curzerenone have shown correlation with more pharmacological indicators. The network predicted that 80 targets were closely related to 10 components, in which 48 targets were connected with 159 metabolic pathways including arachidonic acid metabolism, sphingolipid signaling pathway, and linoleic acid metabolism. Overall, this study provided a scientific basis for TCM quality control to ensure its safety and efficacy.

Therapeutic effects of different polar fractions of hawthorn extract on blood stasis model rats revealed by liquid chromatography-mass spectrometry metabolomics.

Hawthorn, a commonly used traditional Chinese medicine, has been suggested to have therapeutic effects on cardiovascular disease. However, effective fractions of hawthorn extract in the treatment of cardiovascular disease, together with possible therapeutic mechanisms, remain unclear. This study aimed to investigate the effects of four different polar fractions of hawthorn extract on blood stasis model rats, and explore the possible metabolic mechanisms by using a liquid chromatography-mass spectrometry metabolomics approach. Evaluation of hemorheology and fibrinogen showed that n-butanol and ethyl acetate fractions of hawthorn extract had significant therapeutic effects on blood stasis model rats. Furthermore, metabolomics analysis showed that n-butanol and ethyl acetate fractions of hawthorn extract could reverse imbalanced biomarkers in plasma and urine of blood stasis model rats. Additionally, metabolic pathway analysis revealed that plasma biomarkers were responsible for several important pathways, including d-glutamine and d-glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, alanine, aspartate, and glutamate metabolism, sphingolipid metabolism, and arginine biosynthesis. Meanwhile, urine biomarkers were responsible for some important pathways, including phenylalanine metabolism, tyrosine metabolism, and lysine degradation. This study demonstrated that n-butanol and ethyl acetate fractions of hawthorn extract had significant therapeutic effects on blood stasis model rats, and the underlying mechanisms involved multiple metabolic pathways.

Spectroscopic Signature of Red Blood Cells in a D-Galactose-Induced Accelerated Aging Model.

This work presents a semi-quantitative spectroscopic approach, including FTIR-ATR and Raman spectroscopies, for the biochemical analysis of red blood cells (RBCs) supported by the biochemical, morphological and rheological reference techniques. This multi-modal approach provided the description of the RBC alterations at the molecular level in a model of accelerated aging induced by administration of D-galactose (D-gal), in comparison to natural aging. Such an approach allowed to conclude that most age-related biochemical RBC membrane changes (a decrease in lipid unsaturation and the level of phospholipids, or an increase in acyl chain shortening) as well as alterations in the morphological parameters and RBC deformability are well reflected in the D-gal model of accelerated aging. Similarly, as in natural aging, a decrease in LDL level in blood plasma and no changes in the fraction of glucose, creatinine, total cholesterol, HDL, iron, or triglycerides were observed during the course of accelerated aging. Contrary to natural aging, the D-gal model led to an increase in cholesterol esters and the fraction of total esterified lipids in RBC membranes, and evoked significant changes in the secondary structure of the membrane proteins. Moreover, a significant decrease in the phosphorous level of blood plasma was specific for the D-gal model. On the other hand, natural aging induced stronger changes in the secondary structures of the proteins of the RBCs' interior. This work proves that research on the aging mechanism, especially in circulation-related diseases, should employ the D-gal model with caution. Nonetheless, the D-gal model enables to imitate age-related rheological alterations in RBCs, although they are partially derived from different changes observed in the RBC membrane at the molecular level.

Resveratrol Suppresses Severe Acute Pancreatitis-Induced Microcirculation Disturbance through Targeting SIRT1-FOXO1 Axis.

BACKGROUND: Resveratrol (RSV), one of the SIRT1 agonists, has the ability of alleviating severe acute pancreatitis (SAP); however, the concrete protective mechanism remains unknown. It is noteworthy that microcirculation disturbance plays a vital role in SAP, and the SIRT1/FOX1 axis can regulate microcirculation. Therefore, this study is aimed at ascertaining what is the underlying mechanism of the protective effect of RSV on SAP, and whether it is associated with alleviating microcirculation disturbance by regulating the SIRT1/FOX1 axis. METHOD: The model of SAP was induced by retrograde injection of sodium taurodeoxycholate into the bile duct of the rats. The pancreatic wet/dry weight, ET/NO, and TXB2/6-keto-PGF1α ratios; microcirculatory function; and SIRT1 activity were examined. ELISA was used to examine the serum level of lipase, amylase, hemorheology, ET, NO, TXB2, and 6-keto-PGF1α and the content of SIRT1, VEGF, Ang I, and Ang II in the pancreas. RT-PCR was used to examine the mRNA level of VEGF, Ang I, and Ang II. Western blotting was used to detect SIRT1, FOXO1, and acetyl-FOXO1. Immunoprecipitation was used to examine the interaction of SIRT1 and FOXO1. RESULTS: Resveratrol can significantly decrease the expression of lipase, amylase, acetyl-FOXO1, VEGF, Ang II, ET, NO, TXB2, and 6-keto-PGF1α and the ratio of wet/dry weight, ET/NO, and TXB2/6-keto-PGF1α by improving microcirculatory dysfunction and blood viscosity in SAP. Moreover, resveratrol can also promote the interaction of SIRT1 and FOXO1 and increase SIRT1 activity and the expression of SIRT1 and Ang I. The SIRT1 inhibitor, Sirtinol (EX527), obliviously reversed the effects of RSV on SAP. CONCLUSION: Resveratrol can protect rats against SAP, and its protective mechanism is associated with suppressing microcirculation disturbance through activating SIRT1-FOXO1 axis.

Control of vessel diameters mediated by flow-induced outward vascular remodeling in vitro.

Vascular networks consist of hierarchical structures of various diameters and are necessary for efficient blood distribution. Recent advances in vascular tissue engineering and bioprinting have allowed us to construct large vessels, such as arteries, small vessels, such as capillaries and microvessels, and intermediate-scale vessels, such as arterioles, individually. However, little is known about the control of vessel diameters between small vessels and intermediate-scale vessels. Here, we focus on vascular remodeling, which creates lasting structural changes in the vessel wall in response to hemodynamic stimuli, to regulate vessel diameters in vitro. The purpose of this study is to control the vessel diameter at an intermediate scale by inducing outward remodeling of microvessels in vitro. Human umbilical vein endothelial cells and mesenchymal stem cells were cocultured in a microfluidic device to construct microvessels, which were then perfused with a culture medium to induce outward vascular remodeling. We successfully constructed vessels with diameters of 40-150 µm in perfusion culture, whereas vessels with diameters of <20 µm were maintained in static culture. We also revealed that the in vitro vascular remodeling was mediated by NO pathways and MMP-9. These findings provide insight into the regulation of diameters of tissue-engineered blood vessels. This is an important step toward the construction of hierarchical vascular networks within biofabricated three-dimensional systems.

Salvia miltiorrhiza stem-leaf active components of salvianolic acids and flavonoids improved the hemorheological disorder and vascular endothelial function on microcirculation dysfunction rats.

Microcirculation, which connects macrocirculation and cells between arterioles and venules, plays a major role in the early onset of a variety of diseases. In this article, a dextran-induced microcirculation dysfunction (MCDF) model rats were adopted to evaluate the effects and mechanism of Salvia miltiorrhiza stem-leaf extracts based on plasma and urine metabonomics. The results showed the effective components of S. miltiorrhiza stem-leaf could significantly improve the hemorheology and coagulation index of MCDF rats and callback the expression of endothelin-1 (ET-1), induciblenitric oxide synthase (iNOS), vascularendothelial growth factor (VEGF), P-Selectin, thromboxane A2, 6-keto-PGF1α , TNF-α, and interleukin-1ß to control group in MCDF rats. The decrease of microvessel density (MVD) in lung and thymus caused by MCDF was upgraded by Salvia miltiorrhiza stem-leaf. Based on the plasma and urine metabolic data, 20 potential biomarkers were identified. These biomarkers are mainly related to linoleic acid metabolism, glutathione metabolism, pantothenate and coenzyme A biosynthesis, pentose and glucuronate interconversions, pyruvate metabolism, glyoxylate and dicarboxylate metabolism, beta-alanine metabolism, and citrate cycle. The results indicated that the effective components of S. miltiorrhiza stem-leaf can improve the hemorheological disorder and vascular endothelial function. Meanwhile, the effective components can regulate potential biomarkers and correlated metabolic pathway, which can provide guidance for the research and development of new drugs for MCDF.

Efficacy of Isomaltulose Compared to Sucrose in Modulating Endothelial Function in Overweight Adults.

Hyperglycemia is linked to impaired arterial endothelial function (EF), an early sign of cardiovascular disease. We compared the efficacy of low-glycemic index isomaltulose (Palatinose™) with that of sucrose in modulating EF, as assessed by flow-mediated dilation (FMD). In this double-blinded cross-over study, 80 overweight mildly hypertensive subjects were randomized to receive 50 g of either isomaltulose or sucrose. On two non-consecutive days, brachial artery ultrasound FMD scans were obtained prior to and hourly (T0-T3) after carbohydrate load. Blood was drawn immediately after scanning. Glucose and insulin levels were analyzed. Overall, the FMD decrease was attenuated by isomaltulose compared to sucrose (ΔFMD = -0.003% and -0.151%; p > 0.05 for the interaction treatment x period). At T2, FMD was significantly higher after isomaltulose administration compared to that after sucrose administration (FMD = 5.9 ± 2.9% and 5.4 ± 2.6%, p = 0.047). Pearson correlations between FMD and blood glucose showed a trend for a negative association at T0 and T2 independently of the carbohydrate (r-range = -0.20 to -0.23, p < 0.1). Sub-analysis suggested a lower FMD in insulin-resistant (IR) compared to insulin-sensitive subjects. Isomaltulose attenuated the postprandial decline of FMD, particularly in IR persons. These data support the potential of isomaltulose to preserve the endothelial function postprandially and consequently play a favorable role in cardiovascular health.

Erythrocytes morphology and hemorheology in severe bacterial infection.

BACKGROUND: Severe bacterial infections initiate inadequate inflammation that leads to disseminated intravascular coagulation and death. OBJECTIVES: To evaluate the influence of bacterial infection on blood viscosity and red blood cells (RBCs) morphology, and the ability of Calotropis procera proteins (CpLP) to prevent the patho-hemorheology in infected animals. METHODS: Rheology of blood, atomic force microscopy measurements on specific blood elements and blood count were performed to examine changes in blood viscosity, RBCs morphology, platelets activation, and RBCs indices. FINDINGS: Infected mice hold their blood rheological behaviour as compared to that of the control group. However, they presented hyperactivated platelets, RBCs at different stages of eryptosis, and variation on RBCs indices. CpLP administration in healthy animals altered blood behaviour from pseudoplastic to Bingham-like fluid. Such effect disappeared over time and by inhibiting its proteases. No alterations were observed in RBCs morphology or platelets. Treatment of infected animals with CpLP prevented the changes in RBCs indices and morphology. MAIN CONCLUSIONS: The inflammatory process triggered by bacterial infection induced pathological changes in RBCs and platelets activation. Treatment of infected animals with CpLP prevented the emergence of RBCs abnormal morphology and this may have implications in the protective effect of CpLP, avoiding animal death.

Antihyperglycaemic, haemorheological and antioxidant activities of Lychnis chalcedonica L. extract in a streptozotocin-induced rat model of diabetes mellitus.

Background New therapeutic strategies, such as the use of agents to correct rheological disorders, are needed for the prevention and treatment of angiopathy in diabetic patients. The aim of this work was to study the antihyperglycaemic, haemorheologic and antioxidant activities of an extract from the flowering plant Lychnis chalcedonica L. (ELC) and 20-hydroxyecdysone using the streptozotocin-induced model of diabetic rats. Methods The streptozotocin-induced model of diabetes was produced using streptozotocin at a dose of 50 mg/kg (ip). Animals from the experimental groups were treated with ELC (150 mg/kg) or 20-hydroxyecdysone (1.1 mg/kg) intragastrically in 1% aqueous starch mucilage daily, for 14 days; rats of control groups received an equal volume of starch mucilage. The following parameters were measured: glucose concentration (GC) in blood, whole blood viscosity (WBV), conjugated dienes in RBC membranes. Macro- and microrheological indicators (viz. plasma viscosity, haematocrit, RBC aggregation (T1/2) and the RBC elongation index (EI)) were additionally measured in rats that received ELC, and in the control group. Results After treatment with ELC, the GC in rats was 19% lower than that in the control group (14.7 ± 0.9 mM compared to 18.2 ± 1.1 mM). Rats with streptozotocin-induced diabetes have hyperviscosity syndrome, which is characterized by increased WBV, increased RBC aggregation and decreased deformability. ELC treatment reduced WBV at shear rates of 10-90 s-1 by 5-8%, and T1/2 and EI in the experimental group were 31% and 5-10% higher compared to the control group. 20-Hydroxyecdysone decreased WBV at shear rates of 10-90 s-1 by 3-11%. Finally, ELC and 20-hydroxyecdysone lowered the content of conjugated dienes by 27% and by 26% compared to the control groups. Conclusion In the streptozotocin-induced diabetic rat model, ELC showed measurable antihyperglycaemic activity; ELC and 20-hydroxyecdysone demonstrated similar haemorheological, and antioxidant activities.

Investigating the effects and possible mechanisms of danshen- honghua herb pair on acute myocardial ischemia induced by isoproterenol in rats.

Danshen (salvia miltiorrhiza) and honghua(Carthamus tinctorius) were traditional herb pair with promoting blood circulation and removing blood stasis actions, in China. Both were widely used to treat cardiovascular diseases (CVD) for hundreds years, especially shown definite advantage in the treatment of ischemic heart disease (IHD). However, the mechanism of danshen-honghua herb pair (DHHP) in the treatment of IHD was still unclear. This study was focused on examining the effects and possible mechanisms of DHHP in rats with acute myocardial ischemia induced by isoproterenol (ISO). The results suggested that DHHP significantly ameliorated the myocardial tissue abnormalities, notablely inhibited the elevation of lactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST), creatinekinase isoenzyme (CK-MB) and cardiac troponin T (CTn-T) in plasma, obviously decreased the plasma levels of Tumor Necrosis Factor α (TNF-α), outstandingly inhibited the reduction of superoxide dismutase (SOD), catalase (CAT) caused by ISO, significantly inhibited the high expression of Bcl-2 assaciated X protein (Bax) and nuclear transcriptionfactor-κBP65 (NF-κBP65) protein, significantly induced the low expression of B-cell lymphoma-2 (Bcl-2) protein in acute myocardial ischemia rats. DHHP can obviously ameliorate hemodynamic parameters. In summary, DHHP can significantly improve myocardial ischemia in acute myocardial ischemia model rats caused by ISO. Anti-free radicals, anti-peroxidation, inhibition of cell apoptosis and anti- inflammation maybe are the potential mechanisms of DHHP anti-myocardial ischemia in acute myocardial ischemia rats in duced by ISO.

Paeonol protects against hypertension in spontaneously hypertensive rats by restoring vascular endothelium.

The present study focused on the effect of paeonol, one of the main components of Guizhi Fuling Pill, on blood pressure, cerebral blood flow, and vascular endothelium injury in spontaneously hypertensive rats to provide theoretical basis for the treatment of hypertension. After treatment with paeonol, the mean arterial pressure (MAP) of LSHRT and HSHRT rats decreased gradually with the prolongation of treatment time. The systolic blood flow velocity (Vs), diastolic blood flow velocity (Vd) and mean blood flow velocity (Vm) were significantly increased after paeonol treatment (p < 0.05). Paeonol effectively improved the blood pressure and increased the cerebral blood flow velocity in spontaneously hypertensive rats. This may be related to the fact that paeonol reduced the blood viscosity and the oxidative stress and improved the antioxidant capacity. Moreover, paeonol protected vascular endothelial cells and reduced vascular endothelial injury in spontaneously hypertensive rats.

Improved flowing behaviour and gas exchange of stored red blood cells by a compound porous structure.

Storage lesions in red blood cells (RBCs) hinder efficient circulation and tissue oxygenation. The absence of flow mechanics and gas exchange may contribute to this problem. To test if in vitro compensation of flow mechanics and gas exchange helps RBC recovery, three-dimensional polydimethylsiloxane (PDMS) porous structures were fabricated with a sugar mould, simulating lung alveoli. RBC suspensions were passed through the porous structure cyclically, simulating in vivo blood circulation. Acid-base indices, partial gas pressures, ions, glucose and RBC indices were analyzed. An atomic force microscope was used to investigate local mechanical properties of intact RBCs. RBCs suspensions that passed through the porous structures had a higher pH and oxygen partial pressure, and a lower potassium concentration and carbon dioxide partial pressure. Meantime they had better biochemical properties relative to static samples, namely, they exhibited a more homogenous distribution of Young's Modulus. RBCs that passed through a PDMS porous structure were healthier than static ones, giving hints to prevent RBC storage lesions.

Promotion of whole blood rheology after vitamin C supplementation: focus on red blood cells 1.

Hemorheological properties represent significant contributors in the pathogenesis of cardiovascular diseases. As plasma vitamin C is inversely associated with blood viscosity in humans, we aimed to characterize the effect of vitamin C supplementation on hemorheology with an emphasis on erythrocyte functions. Twenty young healthy volunteers were asked to take vitamin C (1000 mg per day) for 3 weeks. We observed beneficial effect of intervention on multiple hemorheological parameters: whole blood viscosity in the range of medium to high shear rates, Casson yield stress, complex viscosity, and storage and loss moduli. As erythrocyte properties play a significant role in hemorheology, we characterized their deformability, nitric oxide production, and sodium pump activity in erythrocyte membranes. We can conclude that observed promotion in whole blood rheology may be consequence of improved erythrocyte functionality as concerns their ability to pass through narrow capillaries of the microcirculation, nitric oxide production, and sodium pump activity. Parameters reflecting oxidative stress and antioxidant status in plasma were not affected by our intervention. As improvement in hemorheology may play an important role in cardioprotection, it would be challenging to investigate the vitamin C supplementation to patients suffering from microcirculatory disturbances and worsened organ perfusion in the case of cardiovascular diseases.

Screening of blood-activating active components from Danshen-Honghua herbal pair by spectrum-effect relationship analysis.

BACKGROUND: Danshen (Salvia miltiorrhiza, DS) and Honghua (Carthamus tinctorius, HH) are commonly used traditional Chinese medicines for activating blood and removing stasis, and DS-HH (DH) herbal pair had potential synergistic effects on promoting blood circulation. Therefore, it is essential to make clear the active components of this herbal pair for better understanding their potential synergistic effects. PURPOSE: To comprehensively evaluate the activity of DH herbal pair on physiological coagulation system of rats, and seek their potential active components by spectrum-effect relationship analysis. METHODS: The water extracts of DH herbal pair with different proportions (DS: HH = 1:1, 2:1, 3:1, 5:1, 1:5 and 1:3) were prepared. Male Sprague-Dawley rats were randomly divided into eight groups: blank group, model group, model + 1:1 (DH) group, model + 2:1 group, model + 3:1 group, model + 5:1 group, model + 1:5 group and model + 1:3 group. The intragastric administration was performed for eight times with 12 h intervals. SC40 semi-automatic coagulation analyzer was employed to determine coagulation indices. Meanwhile, HPLC and LC-MS were applied for chemical analyses of DH extracts. Finally, the active ingredients were screened by spectrum-effect relationship analysis and the activities of major predicted compounds were validated in vitro. RESULTS: Different proportions of DH extracts could significantly prolong thrombin time (TT) and activated partial thromboplastin time (APTT), increase prothrombin time (PT) and decrease fibrinogen (FIB) content, reduced whole blood viscosity (WBV) and plasma viscosity (PV), decreased erythrocyte sedimentation rate blood (ESR) compared with model group. Furthermore, fifteen highly related components were screened out by the spectrum-effect relationship and LC-MS analysis, of which caffeic acid, salvianolic acid B, hydroxysafflor yellow A and lithospermate acid had significant blood-activing effect by prolong APTT and decrease FIB content at high (0.6 mM), medium (0.3 mM) and low (0.15 mM) (except lithospermate acid) concentrations in vitro. CONCLUSIONS: DH herbal pair showed strong blood-activating effect on blood stasis rat through regulating the parameters involved in haemorheology and plasma coagulation system. Four active compounds, caffeic acid, salvianolic acid B, hydroxysafflor yellow A and lithospermate acid predicted by spectrum-effect relationship analysis had good blood-activating effect. Therefore, spectrum-effect relationship analysis is an effective approach for seeking active components in herbal pairs.

Artificial shear stress effects on leukocytes at a biomaterial interface.

Medical devices, such as ventricular assist devices (VADs), introduce both foreign materials and artificial shear stress to the circulatory system. The effects these have on leukocytes and the immune response are not well understood. Understanding how these two elements combine to affect leukocytes may reveal why some patients are susceptible to recurrent device-related infections and provide insight into the development of pump thrombosis. Biomaterials-DLC: diamond-like carbon-coated stainless steel; Sap: single-crystal sapphire; and Ti: titanium alloy (Ti6 Al4 V) were attached to the parallel plates of a rheometer. Whole human blood was left between the two discs for 5 minutes at +37°C with or without the application of shear stress (0 s-1 or 1000 s-1 ). Blood was removed and used for complete blood cell counts, flow cytometry (leukocyte activation, cell death, microparticle generation, phagocytic ability, and reactive oxygen species [ROS] production), and the production of pro-inflammatory cytokines. L-selectin expression on monocytes was decreased when blood was exposed to the biomaterials both with and without shear. Applying shear stress to blood on a Sap and Ti surface led to activation of neutrophils shown as decreased L-selectin expression. Sap and Ti blunted the LPS-stimulated macrophage migration inhibitory factor (MIF) production, most notably when sheared on Ti. The biomaterials used here have been shown to activate leukocytes in a static environment. The introduction of shear appears to exacerbate this activation. Interestingly, a widely accepted biocompatible material (Ti) utilized in many different types of devices has the capacity for immune cell activation and inhibition of MIF secretion when combined with shear stress. These findings contribute to our understanding of the contribution of biomaterials and shear stress to recurrent infections and vulnerability to sepsis in some VAD patients as well as pump thrombosis.

Acute L-Arginine supplementation does not affect red blood cell aggregation and deformability during high intensity interval exercise in healthy men.

BACKGROUND: L-Arginine, the precursor of NO might be involved in improving the cardiovascular disorders via regulation of functional properties of erythrocytes. OBJECTIVE: This study investigated the effects of L-Arginine supplementation on responses of red blood cell (RBC) properties to high intensity interval exercise (HIIE). METHODS: Ten overweight healthy men participated voluntarily in the study and performed two HIIE trials with and without L-Arginine in two separate weeks. The HIIE protocol included 12 intervals of 3-min encompassed 1-min running at 100% of vVO2max and 2-min active recovery at 40% of vVO2max. Three blood samples were taken before and after supplementation, and immediately after exercise; and were used to measure red blood cell properties. RESULTS: The HIIE protocol increased hematocrit, hemoglobin and lactate significantly (P < 0.05), but had no significant effect on RBC aggregation, RBC deformability, and fibrinogen concentration. When data were compared for two trials no significant differences between the responses of RBC properties to two HIIE protocols were detected (P > 0.05), whereas the increases in lactate concentration following HIIE was significantly lower in L-Arginine than placebo trial (P < 0.05). CONCLUSIONS: It is concluded that L-Arginine consumption prior to HIIE does not lead to any improvement in RBC properties during HIIE in overweight healthy men.

Mechanism of Curcuma wenyujin Rhizoma on Acute Blood Stasis in Rats Based on a UPLC-Q/TOF-MS Metabolomics and Network Approach.

Rhizome of Curcuma wenyujin, which is called EZhu in China, is a traditional Chinese medicine used to treat blood stasis for many years. However, the underlying mechanism of EZhu is not clear at present. In this study, plasma metabolomics combined with network pharmacology were used to elucidate the therapeutic mechanism of EZhu in blood stasis from a metabolic perspective. The results showed that 26 potential metabolite markers of acute blood stasis were screened, and the levels were all reversed to different degrees by EZhu preadministration. Metabolic pathway analysis showed that the improvement of blood stasis by Curcuma wenyujin rhizome was mainly related to lipid metabolism (linoleic acid metabolism, ether lipid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and arachidonic acid metabolism) and amino acid metabolisms (tryptophan metabolism, lysine degradation). The component-target-pathway network showed that 68 target proteins were associated with 21 chemical components in EZhu. Five metabolic pathways of the network, including linoleic acid metabolism, sphingolipid metabolism, glycerolipid metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis, were consistent with plasma metabolomics results. In conclusion, plasma metabolomics combined with network pharmacology can be helpful to clarify the mechanism of EZhu in improving blood stasis and to provide a literature basis for further research on the therapeutic mechanism of EZhu in clinical practice.

Rheological properties of sickle erythrocytes in patients with sickle-cell anemia: The effect of hydroxyurea, fetal hemoglobin, and α-thalassemia.

OBJECTIVE: Determine the effect of fetal hemoglobin (HbF) and α-thalassemia on red blood cell (RBC) deformability of patients with sickle-cell anemia (SCA) with and without hydroxyurea (HU). METHODS: Adult patients were enrolled in the Sickle Cell Program of the Cardeza Foundation (Thomas Jefferson University) and were followed up prospectively during the period in which the Multicenter Study of Hydroxyurea (MSH) in patients with SCA was conducted. Ninety-one patients did not receive HU, 20 patients were enrolled in MSH, and 10 patients were enrolled in an open-label study of HU in SCA. Of the 20 patients enrolled in MSH, 11 took HU and nine took placebo. Control group included 113 normal individuals. Red blood cell deformability index (DI) was measured by ektacytometry. RESULTS: Patients with SCA taking HU (n = 21) had higher DI than those taking placebo (n = 9) or who were not taking this therapy (n = 91). In patients without therapy, those with α-thalassemia (n = 31) had higher DI than those without. We showed a significant positive correlation between the level of HbF and DI. SCA patients without α-thalassemia and HbF <10% (n = 48) had lower DI than patients with α-thalassemia and HbF <10% (n = 23) and patients with (n = 8) or without α-thalassemia but with HbF >10% (n = 12). DI measured in patients without α-thalassemia and HbF >10% was higher than in the three other subgroups. CONCLUSION: Elevated levels of HbF with or without HU and α-thalassemia improve sickle RBC rheology, which, in turn, improve the clinical picture of SCA.