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Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to different types of cell death. The degree of irreversible myocardial damage is closely related to age, and ferroptosis is involved in cardiomyocyte damage. However, the mechanisms underlying ferroptosis regulation in aging myocardial I/R injury are still unclear. The present study aims to explore the underlying mechanism of piRNA regulation in ferroptosis. Using left anterior descending coronary artery ligation in an aging rat model and a D-galactose-induced rat cardiomyocyte line (H9C2) to construct an aging cardiomyocyte model, we investigate whether ferroptosis occurs after reperfusion injury in vitro and in vivo. This study focuses on the upregulation of piR-000699 after hypoxia/reoxygenation treatment in aging cardiomyocytes by observing hypoxia/reoxygenation (H/R) injury indicators and ferroptosis-related indicators and clarifying the role of piR-000699 in H/R injury caused by ferroptosis in aging cardiomyocytes. Bioinformatics analysis reveals that SLC39A14 is a gene that binds to piR-000699. Our data show that ferroptosis plays an important role in I/R injury both in vivo and in vitro. Furthermore, the results show the potential role of piR-000699 in regulating SLC39A14 in ferroptosis in aging cardiomyocytes under hypoxia/reoxygenation conditions. Together, our results reveal that the mechanism by which piR-000699 binds to SLC39A14 regulates ferroptosis in aging myocardial I/R injury.

Abstract Objective We investigated the different life styles among the diet structures and exercise patterns of 100 patients with refractory gout and 79 healthy volunteers; of these, we selected 39 patients and 20 healthy volunteers for serum proton magnetic resonance (1H-NMR) metabolic network detection. We determined the potential biomarkers of refractory gout and attempted to explore the relation between potential biomarkers and diet structures and exercise patterns. Methods The study employed a questionnaire survey to analyze diet structures and exercise patterns from 100 patients of refractory gout and 79 healthy volunteers. At the same time, using 1H-NMR metabolic technology to analyze the metabolites present in the serum samples obtained from 39 patients of refractory gout (group B) and 20 healthy subjects (group A). Employing MestReNova (Version 8.0.1) to analyze the metabolites maps, collecting the NMR results, further importing into SIMCA-P+ 14.0 software (Umetrics, Sweden) for principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) statistical analysis. Combining patterns recognition and multivariate statistics, potential biomarkers were searched. Other experimental data, including creatinine and adiponectin, were counted by the SPSS21.0. The measurement data were expressed by X ± S and t test. The counting data were expressed in percent and performed by X 2 test. Results Our results revealed that patients with gout tended to be obese, and there were differences in their lifestyle with exercise, sleep, and smoking, as well as in their preference for fructose drinks, alcohol, and total and structural distribution of meat, milk, eggs, and so on when compared with the healthy volunteers. Importantly, we found the adiponectin in the gout group was lower as compared to the healthy group. Further, metabolomics in combination with KEGG analysis revealed that the biosynthesis of aminoacyl tRNA, biosynthesis of valine, leucine, and isoleucine, metabolism of alanine, aspartic, and glutamate, metabolism of glycine, serine, and threonine, phenylalanine, glycolysis/gluconeogenesis, ketone body synthesis and degradation, metabolism of d‐glutamine, citric acid cycle (TCA cycle), triglyceride metabolism, and others could be used as specific biomarkers of this disease. Conclusion Recurrent refractory gout and formation of tophus may be related to the diet structures and lifestyles between the patients and the healthy people, and their abnormal metabolic network may be related to the disorder of mitochondrial energy metabolism, which further results in abnormal metabolism of glucose, lipids, amino acids, and deposition of uric acid in joints, peripheral connective tissue, and kidney, inducing an inflammatory response.

Objective: This study aimed to use proton nuclear magnetic resonance technology to analyze the metabolic pathways of invigorating the spleen and promoting Yang dehumidification and dredging collaterals (Cassia twig Peony Anemarrhenae and Rise Yang Dehumidification Decoction) in treating the acute attack of refractory gout and to find the target of traditional Chinese medicine (TCM). Method: Forty patients with acute refractory gout of spleen deficiency and dampness-heat type were recruited and randomly divided into TCM group and the Western medicine group, with 20 patients in each group. Serum samples were collected before and after 10 days of treatment for comparative analysis, and the metabolic pathways were identified. Combined with the results of TCM syndrome score, inflammatory indexes (C reactive protein, erythrocyte sedimentation rate), and creatinine, adiponectin, and cytokine (interleukin-6, tumor necrosis factor-α) levels before and after treatment, the mechanism of TCM action was analyzed. Results: Cassia twig Peony Anemarrhenae and Rise Yang Dehumidification Decoction were found to be better than Western medicine in alleviating joint swelling and pain, localized as well as systemic fever, and bitter and dry mouth. Furthermore, inflammatory indicators, cytokines, creatinine, and adiponectin levels were better in the TCM group than in the Western medicine group. In terms of metabolic pathways, the treatment of an acute attack of refractory gout with our TCM compounds resulted in better improvements in branched-chain amino acid (BCAA) metabolism, glycine, serine, and threonine metabolism, tyrosine metabolism, taurine, and low taurine metabolism, glycolysis/sugar dysplasia, synthesis and degradation of ketone body, D-glutamine metabolism, citric acid cycle (TCA cycle), glyceride metabolic pathways, etc., than the use of Western medicine. Conclusion: TCM compounds may improve the metabolic network of refractory acute gout by stimulating the above metabolic pathways to inhibit the inflammatory response, relieve joint pain, and augment glucose metabolism, energy metabolism, and lipid metabolism. These compounds are hence worthy of promotion.

In this study, grey cast iron matrix composites reinforced by different volume fractions of tungsten fibers (Vr = 0.95 %, 1.90 %, 2.85 %, 3.80 %) were investigated in as-cast and under the heat treatment temperatures of 1,000℃ and 1,100℃. The microstructure and mechanical properties of the composites were analyzed and tested by means of SEM, micro-hardness tester and three-point bend testing. The results show that with increasing of the volume fraction of tungsten fibers, the composites reinforced by the tungsten fiber have higher fl exural strength and modulus than that of cast iron without reinforcement, and the fl exural strength increases with the increasing of heat treatment temperatures. Due to diffusion reaction between matrix and reinforcing phases, the process of heat treatment, the number of graphite fl akes in the matrix seemingly becomes lower; and some hard carbide particles are formed around the residual tungsten fi bers. Not only does the hardness of both matrix and reinforcement change tremendously, but also the region of reinforcement is also extended from the original 0.11 mm to 0.19 mm in radius.