Cancer Influences the Elemental Composition of the Myocardium More Strongly than Conjugated Linoleic Acids-Chemometric Approach to Cardio-Oncological Studies.

The aim of the study was to verify in a cardio-oncological model experiment if conjugated linoleic acids (CLA) fed to rats with mammary tumors affect the content of selected macro- and microelements in their myocardium. The diet of Sprague-Dawley females was supplemented either with CLA isomers or with safflower oil. In hearts of rats suffering from breast cancer, selected elements were analyzed with a quadrupole mass spectrometer with inductively coupled plasma ionization (ICP-MS). In order to better understand the data trends, cluster analysis, principal component analysis and linear discriminant analysis were applied. Mammary tumors influenced macro- and microelements content in the myocardium to a greater extent than applied diet supplementation. Significant influences of diet (p = 0.0192), mammary tumors (p = 0.0200) and interactions of both factors (p = 0.0151) were documented in terms of Fe content. CLA significantly decreased the contents of Cu and Mn (p = 0.0158 and p = 0.0265, respectively). The level of Ni was significantly higher (p = 0.0073), which was more pronounced in groups supplemented with CLA. The obtained results confirmed antioxidant properties of CLA and the relationship with Se deposition. Chemometric techniques distinctly showed that the coexisting pathological process induced differences to the greater extent than diet supplementation in the elemental content in the myocardium, which may impinge on cardiac tissue's susceptibility to injuries.

The biological regulatory activities of Flammulina velutipes polysaccharide in mice intestinal microbiota, immune repertoire and heart transcriptome.

The effects of a novel Flammulina velutipes polysaccharide (FVP) on intestinal microbiota, immune repertoire and heart transcriptome were investigated in this study. The results showed that FVP treatment could effectively regulate the abundance of colonic microbiota. And FVP exhibited obvious immunoregulatory effect by influencing V gene and J gene fragments usage on TCRα chain. The usage frequency of TRBV1, TRBJ1-6 and TRBJ1-5 were significantly altered, and 41 V-J pairs were identified with obvious difference after FVP treatment. Furthermore, the mRNA of mice heart was analyzed by transcriptome assay. Total 525 genes and 1587 mRNA were significantly changed after FVP treatment. KEGG annotation indicated that the up-regulated mRNA was enriched in 17 pathways including adherens junction, mTOR signaling pathway, insulin signaling pathway, mitophagy, tight junction, PPAR signaling pathway and TNF signaling pathway, etc. Meanwhile, the down-regulated mRNA was gathered in AMPK signaling pathway, metabolism of xenobiotics by cytochrome P450, apelin signaling pathway, PPAR signaling pathway, PI3K-Akt signaling pathway, insulin signaling pathway, cardiac muscle contraction, adrenergic signaling in cardiomyocytes, Fc gamma R-mediated phagocytosis, etc. The great potential exhibited by FVP could make it an ideal candidate as complementary medicine or functional food for promotion of health.

Low-level embryonic crude oil exposure disrupts ventricular ballooning and subsequent trabeculation in Pacific herring.

There is a growing awareness that transient, sublethal embryonic exposure to crude oils cause subtle but important forms of delayed toxicity in fish. While the precise mechanisms for this loss of individual fitness are not well understood, they involve the disruption of early cardiogenesis and a subsequent pathological remodeling of the heart much later in juveniles. This developmental cardiotoxicity is attributable, in turn, to the inhibitory actions of crude oil-derived mixtures of polycyclic aromatic compounds (PACs) on specific ion channels and other proteins that collectively drive the rhythmic contractions of heart muscle cells via excitation-contraction coupling. Here we exposed Pacific herring (Clupea pallasi) embryos to oiled gravel effluent yielding ΣPAC concentrations as low as ~ 1 µg/L (64 ng/g in tissues). Upon hatching in clean seawater, and following the depuration of tissue PACs (as evidenced by basal levels of cyp1a gene expression), the ventricles of larval herring hearts showed a concentration-dependent reduction in posterior growth (ballooning). This was followed weeks later in feeding larvae by abnormal trabeculation, or formation of the finger-like projections of interior spongy myocardium, and months later with hypertrophy (overgrowth) of the spongy myocardium in early juveniles. Given that heart muscle cell differentiation and migration are driven by Ca2+-dependent intracellular signaling, the observed disruption of ventricular morphogenesis was likely a secondary (downstream) consequence of reduced calcium cycling and contractility in embryonic cardiomyocytes. We propose defective trabeculation as a promising phenotypic anchor for novel morphometric indicators of latent cardiac injury in oil-exposed herring, including an abnormal persistence of cardiac jelly in the ventricle wall and cardiomyocyte hyperproliferation. At a corresponding molecular level, quantitative expression assays in the present study also support biomarker roles for genes known to be involved in muscle contractility (atp2a2, myl7, myh7), cardiomyocyte precursor fate (nkx2.5) and ventricular trabeculation (nrg2, and hbegfa). Overall, our findings reinforce both proximal and indirect roles for dysregulated intracellular calcium cycling in the canonical fish early life stage crude oil toxicity syndrome. More work on Ca2+-mediated cellular dynamics and transcription in developing cardiomyocytes is needed. Nevertheless, the highly specific actions of ΣPAC mixtures on the heart at low, parts-per-billion tissue concentrations directly contravene classical assumptions of baseline (i.e., non-specific) crude oil toxicity.

Outbreak of Oleander (Nerium oleander) Poisoning in Dairy Cattle: Clinical and Food Safety Implications.

Oleander is a spontaneous shrub widely occurring in Mediterranean regions. Poisoning is sporadically reported in livestock, mainly due to the ingestion of leaves containing toxic cardiac glycosides (primarily oleandrin). In this study, 50 lactating Fleckvieh cows were affected after being offered a diet containing dry oleander pruning wastes accidentally mixed with fodder. Clinical examination, electrocardiogram, and blood sampling were conducted. Dead animals were necropsied, and heart, liver, kidney, spleen, and intestine were submitted to histological investigation. Oleandrin detection was performed through ultra-high performance liquid chromatography-tandem mass spectrometry in blood, serum, liver, heart, milk, and cheese samples. Severe depression, anorexia, ruminal atony, diarrhea, serous nasal discharge, tachycardia, and irregular heartbeat were the most common clinical signs. The first animal died within 48 h, and a total of 13 cows died in 4 days. Disseminated hyperemia and hemorrhages, multifocal coagulative necrosis of the cardiac muscle fibers, and severe and diffuse enteritis were suggestive of oleander poisoning. The diagnosis was confirmed by the presence of oleandrin in serum, liver, heart, milk, and cheese. Our results confirm the high toxicity of oleander in cattle and report for the first time the transfer into milk and dairy products, suggesting a potential risk for the consumers.

Fast in vivo detection of myocardial norepinephrine levels in the beating porcine heart.

The sympathetic nervous system modulates cardiac function by controlling key parameters such as chronotropy and inotropy. Sympathetic control of ventricular function occurs through extrinsic innervation arising from the stellate ganglia and thoracic sympathetic chain. In the healthy heart, sympathetic release of norepinephrine (NE) results in positive modulation of chronotropy, inotropy, and dromotropy, significantly increasing cardiac output. However, in the setting of myocardial infarction or injury, sympathetic activation persists, contributing to heart failure and increasing the risk of arrhythmias, including sudden cardiac death. Methodologies for detection of norepinephrine in cardiac tissue are limited. Present techniques rely on microdialysis for analysis by high-performance liquid chromatography coupled to electrochemical detection (HPLC-ED), radioimmunoassay, or other immunoassays, such as enzyme-linked immunosorbent assay (ELISA). Although significant information about the release and action of norepinephrine has been obtained with these methodologies, they are limited in temporal resolution, require large sample volumes, and provide results with a significant delay after sample collection (hours to weeks). In this study, we report a novel approach for measurement of interstitial cardiac norepinephrine, using minimally invasive, electrode-based, fast-scanning cyclic voltammetry (FSCV) applied in a beating porcine heart. The first multispatial and high temporal resolution, multichannel measurements of NE release in vivo are provided. Our data demonstrate rapid changes in interstitial NE profiles with regional differences in response to coronary ischemia, sympathetic nerve stimulation, and alterations in preload/afterload.NEW & NOTEWORTHY Pharmacological, electrical, or surgical regulation of sympathetic neuronal control can be used to modulate cardiac function and treat arrhythmias. However, present methods for monitoring sympathetic release of norepinephrine in the heart are limited in spatial and temporal resolution. Here, we provide for the first time a methodology and demonstration of practice and rapid measures of individualized regional autonomic neurotransmitter levels in a beating heart. We show dynamic, spatially resolved release profiles under normal and pathological conditions.

l-glutamine supplementation exerts cardio-renal protection in estrogen-progestin oral contraceptive-treated female rats.

Glycogen and lipid disruptions represent a spectrum of metabolic disorders that are crucial risk factors for cardiovascular disease in estrogen-progestin oral contraceptive (COC) users. l-glutamine (GLN) has been shown to exert a modulatory effect in metabolic disorders-related syndromes. We therefore hypothesized that GLN supplementation would protect against myocardial and renal glycogen-lipid mishandling in COC-treated animals by modulation of Glucose-6-phosphate dehydrogenase (G6PD) and xanthine oxidase (XO) activities. Adult female Wistar rats were randomly allotted into control, GLN, COC and COC + GLN groups (six rats per group). The groups received vehicle (distilled water, p.o.), GLN (1 g/kg), COC containing 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel and COC plus GLN respectively, daily for 8 weeks. Data showed that treatment with COC led to metabolically-induced obesity with correspondent increased visceral and epicardial fat mass. It also led to increased plasma, myocardial and renal triglyceride, free fatty acid, malondialdehyde (MDA), XO activity, uric acid content and decreased glutathione content and G6PD activity. In addition, COC increased myocardial but not renal glycogen content, and increased myocardial and renal glycogen synthase activity, increased plasma and renal lactate production and plasma aspartate transaminase/alanine aminotransferase (AST/ALT) ratio. However, these alterations were attenuated when supplemented with GLN except plasma AST/ALT ratio. Collectively, the present results indicate that estrogen-progestin oral contraceptive causes metabolically-induced obesity that is accompanied by differential myocardial and renal metabolic disturbances. The findings also suggest that irrespective of varying metabolic phenotypes, GLN exerts protection against cardio-renal dysmetabolism by modulation of XO and G6PD activities.

Lingguizhugan decoction attenuates doxorubicin-induced heart failure in rats by improving TT-SR microstructural remodeling.

BACKGROUND: Lingguizhugan decoction (LGZG), an ancient Chinese herbal formula, has been used to treat cardiovascular diseases in eastern Asia. We investigated whether LGZG has protective activity and the mechanism underlying its effect in an animal model of heart failure (HF). METHODS: A rat model of HF was established by administering eight intraperitoneal injections of doxorubicin (DOX) (cumulative dose of 16 mg/kg) over a 4-week period. Subsequently, LGZG at 5, 10, and 15 mL/kg/d was administered to the rats intragastrically once daily for 4 weeks. The body weight, heart weight index (HWI), heart weight/tibia length ratio (HW/TL), and serum BNP level were investigated to assess the effect of LGZG on HF. Echocardiography was performed to investigate cardiac function, and H&E staining to visualize myocardial morphology. Myocardial ultrastructure and T-tubule-sarcoplasmic reticulum (TT-SR) junctions were observed by transmission electron microscopy. The JP-2 protein level was determined by Western blotting. The mRNA level of CACNA1S and RyR2 and the microRNA-24 (miR-24) level were assayed by quantitative RT-PCR. RESULTS: Four weeks after DOX treatment, rats developed cardiac damage and exhibited a significantly increased BNP level compared with the control rats (169.6 ± 29.6 pg/mL versus 80.1 ± 9.8 pg/mL, P < 0.001). Conversely, LGZG, especially at the highest dose, markedly reduced the BNP level (93.8 ± 17.9 pg/mL, P < 0.001). Rats treated with DOX developed cardiac dysfunction, characterized by a strong decrease in left ventricular ejection fraction compared with the control (58.5 ± 8.7% versus 88.7 ± 4.0%; P < 0.001). Digoxin and LGZG improved cardiac dysfunction (79.6 ± 6.1%, 69.2 ± 2.5%, respectively) and preserved the left ventricular ejection fraction (77.9 ± 5.1, and 80.5 ± 4.9, respectively, P < 0.01). LGZG also improved the LVEDD, LVESD, and FS and eliminated ventricular hypertrophy, as indicated by decreased HWI and HW/TL ratio. LGZG attenuated morphological abnormalities and mitochondrial damage in the myocardium. In addition, a high dose of LGZG significantly downregulated the expression of miR-24 compared with that in DOX-treated rats (fold change 1.4 versus 3.4, P < 0.001), but upregulated the expression of JP-2 and antagonized DOX-induced T-tubule TT-SR microstructural remodeling. These activities improved periodic Ca2+ transients and cell contraction, which may underly the beneficial effect of LGZG on HF. CONCLUSIONS: LGZG exerted beneficial effects on DOX-induced HF in rats, which were mediated in part by improved TT-SR microstructural remodeling.

Potential Role of Leptin in Cardiac Steatosis Induced by Highly Saturated Fat Intake during Adolescence.

SCOPE: To identify the age-dependent effect of diets containing elevated amounts of either saturated or unsaturated fatty acids on cardiac steatosis in mice. METHODS AND RESULTS: Five- and eight-week-old C57BL/6J mice cohorts are given free access to either a saturated or an unsaturated fatty-acid-enriched diet during 8 weeks. Body weight (BW) and food intake are monitored during this period. Cardiac lipid content, carnitine palmitoyltransferase-I (CPT-I) activity, and the amount of uncoupling proteins 2 and 3 (UCP2 and UCP3) are analyzed and correlated with blood leptin concentration. Leptin and PPARγ gene expression is quantified in white adipose tissue (WAT). Both diets have a similar effect on food intake, BW, and adiposity, independently of the age. Nevertheless, cardiac steatosis is specifically identified in adolescent mice consuming the saturated diet. These animals also display lower activity of cardiac CPT-I, a down-regulation of cardiac UCP2, together with lower concentration of plasma leptin. Accordingly, leptin gene expression is reduced in the visceral WAT. CONCLUSION: Consumption of diets containing elevated amounts of saturated fat during adolescence and early adult life promotes cardiac steatosis in mice. An insufficient endocrine activity of WAT, in terms of leptin production, may account for such an effect.

DHA Cycling Halves the DHA Supplementation Needed to Maintain Blood and Tissue Concentrations via Higher Synthesis from ALA in Long-Evans Rats.

BACKGROUND: Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) recommendations are frequently stated at 500 mg/d; however, adherence to these recommendations would result in a large global commercial EPA/DHA production deficit. Previously, our laboratory demonstrated that acute DHA intake in rats can increase the capacity for synthesis-secretion of n-3 (ω-3) polyunsaturated fatty acids (PUFAs). OBJECTIVE: We aimed to investigate the utility of a dietary DHA cycling strategy that employs 2 wk of repeated DHA feeding for a total of 3 cycles over 12 wk. METHODS: Male Long-Evans rats were fed a 10% fat diet by weight comprised of either 1) a 2-wk, 2% α-linolenic acid (ALA, DHA-ALA group 18:3n-3) diet followed by a 2-wk, 2% DHA + 2% ALA diet over 3 consecutive 4-wk periods ("DHA cycling," DHA-ALA group); 2) a 2% DHA + 2% ALA diet (DHA group) for 12 wk; or 3) a 2% ALA-only diet (ALA group) for 12 wk. At 15 wk old, blood and tissue fatty acid concentrations and liver mRNA expression and 13C-DHA natural abundances were determined. RESULTS: DHA concentrations in plasma, erythrocytes, and whole blood between the DHA-ALA group and the DHA groups were not different (P ≥ 0.05), but were 72-110% higher (P < 0.05) than in the ALA group. Similarly, DHA concentrations in liver, heart, adipose, and brain were not different (P ≥ 0.05) between the DHA-fed groups, but were at least 62%, 72%, 320%, and 68% higher (P < 0.05) than in the ALA group in liver, heart, adipose, and skeletal muscle, respectively. Compound-specific isotope analysis indicated that 310% more liver DHA in the DHA-ALA group compared with the DHA group is derived from dietary ALA, and this was accompanied by a 123% and 93% higher expression of elongation of very long-chain (Elovl)2 and Elovl5, respectively, in the DHA-ALA group compared with the ALA group. CONCLUSIONS: DHA cycling requires half the dietary DHA while achieving equal blood and tissue DHA concentrations in rats. Implementation of such dietary strategies in humans could reduce the gap between global dietary n-3 PUFA recommendations and commercial production.

Myocardial iron homeostasis and hepcidin expression in a rat model of heart failure at different levels of dietary iron intake.

BACKGROUND: Up to 50% of patients with chronic heart failure (HF) have systemic iron deficiency, which contributes to symptoms and poor prognosis. Myocardial iron deficiency (MID) in HF patients has been recently documented, but its causes and consequences are unknown. The goal of our study was to address these questions in a well-defined rat HF model induced by volume overload due to aorto-caval fistula. METHODS: Modulation of dietary iron content in a rat model of HF has been used to address how iron status affects cardiac iron levels, heart structure and function, and how the presence of HF affects cardiac expression of hepcidin and other iron-related genes. RESULTS: MID developed in the rat model of heart failure. Iron supplementation did not normalize the myocardial iron content; however, it improved survival of HF animals compared to animals fed diet with normal iron content. We observed marked upregulation of hepcidin mRNA expression in HF animals, which was not associated with systemic or cardiac iron levels but strongly correlated with markers and parameters of heart injury. Identical iron-independent pattern was observed for expression of several iron-related genes. CONCLUSIONS: MID is not caused by defective iron absorption or decreased systemic iron levels, but rather by intrinsic myocardial iron deregulation. Altered cardiac expression of hepcidin and other iron-related genes is driven by iron-independent stimuli in the failing heart. GENERAL SIGNIFICANCE: Understanding of the causes and consequences of MID is critical for finding strategies how to improve cardiac iron stores and in HF patients.

Protective Effect of Resveratrol against Ischemia-Reperfusion Injury via Enhanced High Energy Compounds and eNOS-SIRT1 Expression in Type 2 Diabetic Female Rat Heart.

Type 2 diabetic women have a high risk of mortality via myocardial infarction even with anti-diabetic treatments. Resveratrol (RSV) is a natural polyphenol, well-known for its antioxidant property, which has also shown interesting positive effects on mitochondrial function. Therefore, we aim to investigate the potential protective effect of 1 mg/kg/day of RSV on high energy compounds, during myocardial ischemia-reperfusion in type 2 diabetic female Goto-Kakizaki (GK) rats. For this purpose, we used 31P magnetic resonance spectroscopy in isolated perfused heart experiments, with a simultaneous measurement of myocardial function and coronary flow. RSV enhanced adenosine triphosphate (ATP) and phosphocreatine (PCr) contents in type 2 diabetic hearts during reperfusion, in combination with better functional recovery. Complementary biochemical analyses showed that RSV increased creatine, total adenine nucleotide heart contents and citrate synthase activity, which could be involved in better mitochondrial functioning. Moreover, improved coronary flow during reperfusion by RSV was associated with increased eNOS, SIRT1, and P-Akt protein expression in GK rat hearts. In conclusion, RSV induced cardioprotection against ischemia-reperfusion injury in type 2 diabetic female rats via increased high energy compound contents and expression of protein involved in NO pathway. Thus, RSV presents high potential to protect the heart of type 2 diabetic women from myocardial infarction.

Does Sericin, as a Novel Pleurodesis Agent, Have Higher Effectiveness Compared to Talcum Powder, Doxycycline, and Silver Nitrate Pleurodesis?

INTRODUCTION: The usefulness of sericin as pleurodesis agent has previously been described. Present study aims to compare sericin pleurodesis regarding success, effectiveness, tolerability, and side-effects. METHODS: Adult, 12-week-old Wistar-albino rats (n=60), divided to five groups as sericin, talcum-powder, doxycycline, silver-nitrate and control. Agents were administrated through left thoracotomy, rats sacrificed twelve-days after. RESULTS: Highest ratio of collagen fibers was observed in sericin group, and the intensity was higher than talcum-powder group (p<0.05). Compared to silver nitrate, sericin group displayed better mesothelial reaction, and multi-layer mesothelium was also better (p<0.05). Foreign body reaction and emphysema were less frequent in sericin group (p<0.05). The presence of biological tissue in parenchyma was less prominent in sericin group (p<0.05). Foreign body reaction on thoracic wall was less common in sericin group (p<0.05). Presence of biological tissue glue in thoracic wall was less prominent in sericin group (p<0.05). Glomerular degeneration was lower in sericin group compared to the silver nitrate group (p<0.05), and tubular degeneration was less common in sericin group than talcum group (p<0.05). Pericarditis was less common in sericin group compared to the other groups (p<0.05). CONCLUSION: As an intrinsic, natural glue protein, sericin protects the lung parenchyma and tissues, and its glue-like characteristics enable pleurodesis. The success of sericin in pleurodesis was demonstrated in the present study based on investigations of the pleurae. Being cost-effective and better tolerated agent associated with a low potential of side effects, sericin is more effective, less expensive and provides more lung parenchyma protection.

The protective effect of Er-Xian decoction against myocardial injury in menopausal rat model.

BACKGROUND: Er-Xian decoction (EXD), a formula of Chinese medicine, is often used to treat menopausal syndrome in China. The aim of the present study was to explore the potential cardioprotective mechanism of EXD against myocardial injury in an ovariectomy-induced menopausal rat model. METHODS: We divided the female Wistar rats into ovariectomy group and sham operation group (SHAM group). The ovariectomized (OVX) rats received treatment of vehicle (OVX group), EXD (EXD group) or 17ß-estradiol (E2 group). After 12-week of treatment, the level of estradiol in serum was detected using an electrochemiluminescence immunoassay, and electrophysiologic changes in myocardial action potentials (AP) were evaluated using intracellular microelectrode technique. Changes in the histopathology of the left ventricle and the ultrastructure of the cardiomyocytes were observed by hematoxylin and eosin (HE) staining and transmission electronmicroscopy to assess myocardial injury. Microarrays were applied for the evaluation of gene expression profiles in ventricular muscle of the OVX and EXD rats. Further pathway analyses of the differential expression genes were carried out using the Kyoto Encyclopedia of Genes and Genomes (KEGG). And real-time quantitative RT-PCR (qRT-PCR) was used for verification of the key findings. RESULTS: The results from electrophysiological and histomorphological observations demonstrated that EXD had a substantial myocardial protective effect. The EXD-treated rats, in comparison with the OVX rats, demonstrated up-regulated expression of 28 genes yet down-regulated expression of 157 genes in the ventricular muscle. The qRT-PCR assay validated all selected differential expression genes. The KEGG pathway analysis showed that the down-regulated genes were relevant to cardiomyopathy and myocardial contractility. EXD could decrease the mRNA expressions of cardiac myosin (Myh7, Myl2) and integrin (Itgb5) in the ventricular myocardium. CONCLUSION: EXD had a protective effect against myocardial injury in OVX rats, and this cardioprotective effect may be associated with modulation of the expression of cardiac myosin or integrin at the mRNA level.

Influence of Low-Intensive Red Light on the Myocardium in Experimental Asphyxia.

We studied the effects of low-intensity broadband red light on electrical activity of the heart and oxidative modification of proteins in the myocardium of rats after asphyxia. It was shown that low-intensity red light reduced the content of oxidatively modified proteins in rat heart after oxidative stress caused by asphyxia. Exposure to low-intensity red light normalized ECG parameters in rats after asphyxia.

Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia.

BACKGROUND: Beta thalassaemia is a common inherited blood disorder. The need for frequent blood transfusions in this condition poses a difficult problem to healthcare systems. The most common cause of morbidity and mortality is cardiac dysfunction from iron overload. The use of iron chelation therapy has reduced the severity of systemic iron overload but specific, non-toxic treatment is required for removal of iron from the myocardium. OBJECTIVES: To assess the effects of calcium channel blockers combined with standard iron chelation therapy in people with transfusion-dependent beta thalassaemia on the amount of iron deposited in the myocardium, on parameters of heart function, and on the incidence of severe heart failure or arrhythmias and related morbidity and mortality. SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched ongoing trials databases, and the reference lists of relevant articles and reviews.Date of last search: 24 February 2018. SELECTION CRITERIA: We included randomised controlled trials of calcium channel blockers combined with standard chelation therapy compared with standard chelation therapy alone or combined with placebo in people with transfusion-dependent beta thalassaemia. DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion criteria for the selection of trials. Two authors assessed the risk of bias of trials and extracted data and a third author verified these assessments. The authors used the GRADE system to assess the quality of the evidence. MAIN RESULTS: Two randomised controlled trials (n = 74) were included in the review; there were 35 participants in the amlodipine arms and 39 in the control arms. The mean age of participants was 24.4 years with a standard deviation of 8.5 years. There was comparable participation from both genders. Overall, the risk of bias in included trials was low. The quality of the evidence ranged across outcomes from low to high, but the evidence for most outcomes was judged to be low quality.Cardiac iron assessment, as measured by heart T2*, did not significantly improve in the amlodipine groups compared to the control groups at six or 12 months (low-quality evidence). However, myocardial iron concentration decreased significantly in the amlodipine groups compared to the control groups at both six months, mean difference -0.23 mg/g (95% confidence interval -0.07 to -0.39), and 12 months, mean difference -0.25 mg/g (95% confidence interval -0.44 to -0.05) (low-quality evidence). There were no significant differences between treatment and control groups in serum ferritin (low-quality evidence), liver T2* (low-quality evidence), liver iron content (low-quality evidence) and left ventricular ejection fraction (low-quality evidence). There were no serious adverse events reported in either trial; however, one trial (n = 59) reported mild adverse events, with no statistically significant difference between groups (low-quality evidence). AUTHORS' CONCLUSIONS: The available evidence does not clearly suggest that the use of calcium channel blockers is associated with a reduction in myocardial iron in people with transfusion-dependent beta thalassaemia, although a potential for this was seen. There is a need for more long-term, multicentre trials to assess the efficacy and safety of calcium channel blockers for myocardial iron overload, especially in younger children. Future trials should be designed to compare commonly used iron chelation drugs with the addition of calcium channel blockers to investigate the potential interplay of these treatments. In addition, the role of baseline myocardial iron content in affecting the response to calcium channel blockers should be investigated. An analysis of the cost-effectiveness of the treatment is also required.

Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization.

Despite improvements in pre-clinical drug testing models, predictability of clinical outcomes continues to be inadequate and costly due to poor evidence of drug metabolism. Humanized miniature organs integrating decellularized rodent organs with tissue specific cells are translational models that can provide further physiological understanding and evidence. Here, we evaluated 4-Flow cannulated rat hearts as the fundamental humanized organ model for cardiovascular drug validation. Results show clearance of cellular components in all chambers in 4-Flow hearts with efficient perfusion into both coronary arteries and cardiac veins. Furthermore, material characterization depicts preserved organization and content of important matrix proteins such as collagens, laminin, and elastin. With access to the complete vascular network, different human cell types were delivered to show spatial distribution and integration into the matrix under perfusion for up to three weeks. The feature of 4-Flow cannulation is the preservation of whole heart conformity enabling ventricular pacing via the pulmonary vein as demonstrated by noninvasive monitoring with fluid pressure and ultrasound imaging. Consequently, 4-Flow hearts surmounting organ mimicry challenges with intact complexity in vasculature and mechanical compliance of the whole organ providing an ideal platform for improving pre-clinical drug validation in addition to understanding cardiovascular diseases.

Impact of flaxseed and soy nuts as dietary supplements on lipid profile, insulin sensitivity, and GLUT4 expression in ovariectomized rats.

We assessed the effects of a diet with flaxseed or soy nuts versus estradiol on the lipid profile, insulin sensitivity, and glucose transporter type 4 (GLUT4) expression in ovariectomized female rats. Forty-four female Wistar rats (90 days old) underwent ovariectomy and were divided into 4 groups: C (standard diet), E (standard diet + subcutaneous 17ß-estradiol pellets), L (standard diet + flaxseed + subcutaneous placebo pellets), and S (standard diet + soy nuts + subcutaneous placebo pellets). Customized diets and the insertion of pellets were started 21 days after ovariectomy and were continued for another 21 days. We measured body mass, insulin tolerance, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and GLUT4 (in cardiac and adipose tissues). We found a lower body mass and a lower Lee index in group E and a trend toward improved insulin sensitivity in group S (p = 0.066). Groups L and S showed a better lipid profile when compared with group C. Microsomal GLUT4 increased in group L (in cardiac and adipose tissues), and plasma membrane GLUT4 increased in groups E, L, and S (in both tissues). We conclude that flaxseed and soy nuts as dietary supplements improve lipid profile and increase GLUT4 expression.

iTRAQ-Based Proteomic Analysis Reveals Recovery of Impaired Mitochondrial Function in Ischemic Myocardium by Shenmai Formula.

Shenmai formula (SM) has been a traditional medicinal remedy for treating cardiovascular diseases in China for 800 years; however, its mechanism of action remains unclear. To explore the mechanism underlying cardioprotective effects of SM, iTRAQ-based proteomic approach was applied to analyze protein of myocardium in rats with myocardial ischemic injury. Upon treatment with SM and its two major components Red ginseng (RG) and Radix Ophiopogonis (OP), 101 differentially expressed proteins were filtered from a total of 712 detected and annotated proteins. They can be classified according to their locations and functions, while most of them are located in intracellular organelle, participating in cellular metabolic process. The functions of them are mostly associated with mitochondrial oxidative phosphorylation/respiration. The differentially expressed proteins were validated by liquid chromatography-tandem mass spectrometry and Western blotting (ATP5D, NDUFB10, TNNC1). Further in vitro experiments found that SM could attenuate hypoxia induced impairment of mitochondrial membrane potential and cellular ATP concentration in neonatal rat ventricular myocytes. Interestingly, the result of quantitative mitochondrial biogenesis assays revealed that SM had dominant positive effects on the maximum respiration, ATP-coupled respiration, and spare capacity of mitochondria in response to hypoxia. Hence, our findings suggest that SM promotes mitochondrial function to protect cardiomyocytes against hypoxia, which provides a possible illustration for conventional botanical therapy on a molecular level.

Public health risk of trace metals in fresh chicken meat products on the food markets of a major production region in southern China.

Because most chickens are reared in intensive farms, where a range of feed additives are used routinely, concerns have been raised on the potential public health risk of chicken product consumption. This study was conducted to characterize the contents of trace metals in fresh chicken tissues (354 samples) on the food markets in Guangdong province of southern China, a major region of chicken production with heavy per capita chicken consumption, and to assess the public health risk from chronic dietary exposure to the trace metals through chicken consumption. With the exception of Cr, Ni, and Pb, the contents of trace metals were generally higher in the chicken giblets (livers, gizzards, hearts, and kidneys) compared to muscles (breasts and drumsticks). Chicken tissues from the urban markets generally contained higher levels of As, Cu, Mn, and Zn than those from the rural markets, while the contents of Pb were typically higher in the chicken muscles from the rural markets. Results of statistical analyses indicate that Cu, Zn, and As in the chicken tissues derived mainly from the feeds, which is consistent with the widespread use of Cu, Zn, and phenylarsenic compounds as feed supplements/additives in intensive poultry farming. No non-carcinogenic risk is found with the consumption of fresh chicken meat products on the food markets, while approximately 70% of the adult population in Guangzhou and 30% of those in Lianzhou have bladder and lung cancer risk above the serious or priority level (10-4), which arises from the inorganic arsenic contained in the chicken tissues. These findings indicate that the occurrence of inorganic arsenic at elevated levels in chicken tissues on the food markets in Guangdong province poses a significant public health risk, thus the use of phenylarsenic feed additives in China's poultry farming should be significantly reduced and eventually phased out.

Altered Potassium Ion Channel Function as a Possible Mechanism of Increased Blood Pressure in Rats Fed Thermally Oxidized Palm Oil Diets.

Intake of thermally oxidized palm oil leads to cytotoxicity and alteration of the potassium ion channel function. This study investigated the effects of fresh and thermally oxidized palm oil diets on blood pressure and potassium ion channel function in blood pressure regulation. Male Wistar rats were randomly divided into three groups of eight rats. Control group received normal feed; fresh palm oil (FPO) and thermally oxidized palm oil (TPO) groups were fed a diet mixed with 15% (weight/weight) fresh palm oil and five times heated palm oil, respectively, for 16 weeks. Blood pressure was measured; blood samples, hearts, and aortas were collected for biochemical and histological analyses. Thermally oxidized palm oil significantly elevated basal mean arterial pressure (MAP). Glibenclamide (10-5 mmol/L) and tetraethylammonium (TEA; 10-3 mmol/L) significantly raised blood pressure in TPO compared with FPO and control groups. Levcromakalim (10-6 mmol/L) significantly (p < .01) reduced MAP by 32.0% in FPO and by 5.4% in TPO. NS1619 (10 mmol/L) significantly (p < .01) decreased MAP by 19.5% in FPO and by 8% in TPO. The TPO significantly (p < 0.01) increased the tissue levels of peroxide, total cholesterol, triglyceride, and low-density lipoprotein cholesterol while catalase and superoxide dismutase activities were significantly (p < .01) decreased compared with control and FPO groups. Histological alterations were prominent in aortas and hearts of rats in the TPO group. These results suggest that prolonged consumption of repeatedly heated palm oil increases MAP probably due to the attenuation of adenosine triphosphate-sensitive potassium (KATP) and large-conductance calcium-dependent potassium (BKCa) channels, tissue peroxidation, and altered histological structures of the heart and blood vessels.