Creatine nitrate supplementation strengthens energy status and delays glycolysis of broiler muscle via inhibition of LKB1/AMPK pathway.

This study aimed to evaluate the effects of dietary creatine nitrate (CrN) on growth performance, meat quality, energy status, glycolysis, and related gene expression of liver kinase B1/AMP-activated protein kinase (LKB1/AMPK) pathway in Pectoralis major (PM) muscle of broilers. A total of 240 male Arbor Acres broilers (28-day-old) were randomly allocated to one of 5 dietary treatments: the basal diet (control group), and the basal diets supplemented with 600 mg/kg guanidinoacetic acid (GAA), 300, 600, or 900 mg/kg CrN (identified as GAA600, CrN300, CrN600, or CrN900, respectively). We found that dietary GAA and CrN supplementation for 14 d from d 28 to 42 did not affect broiler growth performance, carcass traits, and textural characteristics of breast muscle. GAA600, CrN600, and CrN900 treatments increased pH24h and decreased drip loss of PM muscle compared with the control (P < 0.05). The PM muscles of CrN600 and CrN900 groups showed higher glycogen concentration and lower lactic acid concentration accompanied by lower activities of phosphofructokinase (PFK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) (P < 0.05). Simultaneously, GAA600 and all CrN treatments increased concentration of muscle creatine, phosphocreatine (PCr) and ATP, and decreased AMP concentration and AMP/ATP ratio (P < 0.05). Meanwhile, the concentrations of muscle creatine, PCr, and ATP were increased linearly, while muscle AMP concentration and AMP/ATP ratio were decreased linearly and quadratic as the dose of CrN increased (P < 0.05). GAA600, CrN600, and CrN900 treatments upregulated mRNA expression of CreaT in PM muscle, and CrN600 and CrN900 treatments downregulated GAMT expression in liver and PM muscle compared with the control or GAA600 groups (P < 0.05). The mRNA expression of muscle LKB1, AMPKα1, and AMPKα2 was downregulated linearly in response to the increasing CrN level (P < 0.05). Overall, CrN showed better efficacy on strengthening muscle energy status and improve meat quality than GAA at the some dose. These results indicate that CrN may be a potential replacement for GAA as a new creatine supplement.

[24 hours urinary sodium and potassium excretion and association with blood pressure among people aged 18-75 years old in six Chinese provinces].

Objective: To analyze the level of sodium and potassium intake and their association with blood pressure among people aged 18 to 75 years old in six provinces. Methods: From October to December 2018, participants aged 18 to 75 years were selected from Hebei, Hunan, Sichuan, Jiangxi, Qinghai and Heilongjiang provinces by using cluster random sampling method. Demographic characteristics and lifestyle information were collected by using questionnaire survey. Physical measurement and 24-hour urine collection were also conducted. Results: A total of 2 636 subjects were finally included in the analysis. The average urine sodium, potassium and sodium-to-potassium molar ratio were(4 438.4±1 822.8)mg/d, (1 566.2±646.3)mg/d, and 5.2±2.2, respectively. According to World Health Organization standards, 94.5% and 98.7% of the respondents had excessive sodium intake and insufficient potassium intake. After adjusting for related factors, each 1 000 mg increase in sodium excretion was associated with increased systolic blood pressure (1.65 mmHg, 95%CI: 1.07, 2.22) and diastolic blood pressure (0.53 mmHg, 95%CI: 0.21, 0.84), and each 1 000 mg increase in potassium excretion was associated with decreased systolic blood pressure (3.02 mmHg, 95%CI:-4.25, -1.80) and diastolic blood pressure (1.27 mmHg, 95%CI:-2.05, -0.48). Conclusion: The sodium intake in Chinese population remains excessive and potassium intake is insufficient. Sodium and potassium could be associated with blood pressure and the intervention of reducing sodium and supplementing potassium should be conducted in the corresponding population.

Dunye Guanxinning Improves Acute Myocardial Ischemia-Reperfusion Injury by Inhibiting Neutrophil Infiltration and Caspase-1 Activity.

Acute myocardial infarction is the most serious manifestation of cardiovascular disease, and it is a life-threatening condition. Dunye Guanxinning (DG) is a protective traditional Chinese patent herbal medicine with high clinical efficacy and suitable for the treatment of myocardial infarction. However, the mechanism through which it is beneficial is unclear. In this study, we hypothesized that DG improves acute myocardial ischemia-reperfusion injury by inhibiting neutrophil infiltration and caspase-1 activity. We found that DG administration decreased infarct size and cardiomyocyte apoptosis and improved left ventricular ejection fraction, fractional shortening, end-systolic volume index, end-systolic diameter, and carotid arterial blood flow output in rats. DG administration also improved hemorheological parameters, myocardial damage biomarkers, and oxidative stress indexes. The findings showed that DG administration inhibited neutrophil infiltration and reduced the serum interleukin-1 beta (IL-1ß) level and myocardial IL-1ß maturation. Moreover, DG administration inhibited caspase-1 activity and activated adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in rat hearts. These results suggested that DG administration inhibits inflammasome activity and IL-1ß release through the AMPK pathway. Our findings support the clinical efficacy of DG and partially reveal its mechanism, which is beneficial for understanding the therapeutic effects of this protective traditional Chinese patent drug.

Fibroblast biology. Signals targeting the synovial fibroblast in arthritis.

Fibroblast-like cells in the synovial lining (type B lining cells), stroma and pannus tissue are targeted by many signals, such as the following: ligands binding to cell surface receptors; lipid soluble, small molecular weight mediators (eg nitric oxide [NO], prostaglandins, carbon monoxide); extracellular matrix (ECM)-cell interactions; and direct cell-cell contacts, including gap junctional intercellular communication. Joints are subjected to cyclic mechanical loading and shear forces. Adherence and mechanical forces affect fibroblasts via the ECM (including the hyaluronan fluid phase matrix) and the pericellular matrix (eg extracellular matrix metalloproteinase inducer [EMMPRIN]) matrices, thus modulating fibroblast migration, adherence, proliferation, programmed cell death (including anoikis), synthesis or degradation of ECM, and production of various cytokines and other mediators [1]. Aggressive, transformed or transfected mesenchymal cells containing proto-oncogenes can act in the absence of lymphocytes, but whether these cells represent regressed fibroblasts, chondrocytes or bone marrow stem cells is unclear.

Expression of stem cell factor (SCF) and SCF receptor (c-kit) in synovial membrane in arthritis: correlation with synovial mast cell hyperplasia and inflammation.

OBJECTIVE: Stem cell factor (SCF), the ligand for the SCF receptor (c-kit) expressed on precursors and mature mast cells (MC), is a major agonist for human MC (e.g., SCF induces MC development, chemotaxis, activation, proliferation of MC precursors, mediates MC adhesion, and changes MC releasability). We investigated expression of SCF and c-kit in synovial membrane with particular reference to the mechanism of local MC hyperplasia and inflammation in arthritis. METHODS: We conducted single and double labeling immunohistochemistry (ABC, APAAP, indirect immunofluorescence techniques) with antibodies to SCF, c-kit, MC tryptase, Ki-67 antigen (marker for proliferating cells), and CD68 (monocyte/macrophage marker). Synovial specimens analyzed were from 31 patients: traumatic arthritis (TrA, n=9), osteoarthritis (OA, n=12), and rheumatoid arthritis (RA, n=10). Control experiments were performed on human lung, skin, and buccal mucosa tissues, on the HMC-1 mast cell line, and isolated lung MC. Morphometry was performed by computerized image analysis. RESULTS: Synovial c-kit expression was found to be restricted to MC, whereas SCF is detected in synovial lining cells, stromal fibroblasts, monocyte/macrophages, endothelial cells, and in vascular basement membranes. SCF staining was localized to MC as well, but it was not possible to specify whether this represents SCF produced by or bound (via c-kit) to MC. In inflamed synovial membranes/areas, SCF was found to be redistributed into the extracellular matrix. Redistribution of SCF was accompanied by degranulation and/or accumulation of c-kit+ MC, the hyperplasia of which correlated positively with histologic inflammation/inflammatory cell densities, but did not appear to involve MC proliferation in situ. These findings appeared to be common for all the conditions (TrA, OA, RA) studied. CONCLUSION: In addition to the demonstration/characterization of SCF and c-kit protein expression in human synovium, results of this study suggest the hypothesis that, in arthritis, local mobilization of SCF may play a role in the development of synovial MC hyperplasia without inducing in situ proliferation of MC, and that the synovial SCF/MC c-kit system may contribute to the local nonspecific inflammatory response/arthritic flares in TrA, OA, and RA.