Complex metabolic interactions between ovary, plasma, urine, and hair in ovarian cancer.

Ovarian cancer (OC) is the third most common malignant tumor of women accompanied by alteration of systemic metabolism, yet the underlying interactions between the local OC tissue and other system biofluids remain unclear. In this study, we recruited 17 OC patients, 16 benign ovarian tumor (BOT) patients, and 14 control patients to collect biological samples including ovary plasma, urine, and hair from the same patient. The metabolic features of samples were characterized using a global and targeted metabolic profiling strategy based on Gas chromatography-mass spectrometry (GC-MS). Principal component analysis (PCA) revealed that the metabolites display obvious differences in ovary tissue, plasma, and urine between OC and non-malignant groups but not in hair samples. The metabolic alterations in OC tissue included elevated glycolysis (lactic acid) and TCA cycle intermediates (malic acid, fumaric acid) were related to energy metabolism. Furthermore, the increased levels of glutathione and polyunsaturated fatty acids (linoleic acid) together with decreased levels of saturated fatty acid (palmitic acid) were observed, which might be associated with the anti-oxidative stress capability of cancer. Furthermore, how metabolite profile changes across differential biospecimens were compared in OC patients. Plasma and urine showed a lower concentration of amino acids (alanine, aspartic acid, glutamic acid, proline, leucine, and cysteine) than the malignant ovary. Plasma exhibited the highest concentrations of fatty acids (stearic acid, EPA, and arachidonic acid), while TCA cycle intermediates (succinic acid, citric acid, and malic acid) were most concentrated in the urine. In addition, five plasma metabolites and three urine metabolites showed the best specificity and sensitivity in differentiating the OC group from the control or BOT groups (AUC > 0.90) using machine learning modeling. Overall, this study provided further insight into different specimen metabolic characteristics between OC and non-malignant disease and identified the metabolic fluctuation across ovary and biofluids.

Exercise Enhanced Cardiac Function in Mice With Radiation-Induced Heart Disease via the FNDC5/Irisin-Dependent Mitochondrial Turnover Pathway.

Background: Despite the development of radiation therapy (RT) techniques, concern regarding the serious and irreversible heart injury induced by RT has grown due to the lack of early intervention measures. Although exercise can act as an effective and economic nonpharmacologic strategy to combat fatigue and improve quality of life for cancer survivors, limited data on its application in radiation-induced heart disease (RIHD) and the underlying molecular mechanism are available. Methods: Fifteen young adult male mice were enrolled in this study and divided into 3 groups (including exercised RIHD group, sedentary RIHD group, and controls; n =5 samples/group). While the mice in the control group were kept in cages without irradiation, those in the exercised RIHD group underwent 3weeks of aerobic exercise on the treadmill after radiotherapy. At the end of the 3rd week following RT, FNDC5/irisin expression, cardiac function, aerobic fitness, cardiomyocyte apoptosis, mitochondrial function, and mitochondrial turnover in the myocardium were assessed to identify the protective role of exercise in RIHD and investigate the potential mechanism. Results: While sedentary RIHD group had impaired cardiac function and aerobic fitness than controls, the exercised RIHD mice had improved cardiac function and aerobic fitness, elevated ATP production and the mitochondrial protein content, decreased mitochondrial length, and increased formation of mitophagosomes compared with sedentary RIHD mice. These changes were accompanied by the elevated expression of FNDC5/irisin, a fission marker (DRP1) and mitophagy markers (PINK1 and LC3B) in exercised RIHD group than that of sedentary RIHD group, but the expression of biogenesis (TFAM) and fusion (MFN2) markers was not significantly changed. Conclusion: Exercise could enhance cardiac function and aerobic fitness in RIHD mice partly through an autocrine mechanism via FNDC5/irisin, in which autophagy was selectively activated, suggesting that FNDC5/irisin may act as an intervening target to prevent the development of RIHD.

A systematic review and meta-analysis of catheter ablation for atrial fibrillation.

BACKGROUND: This study analyzes and compares the efficacy of using catheter ablation (CA) and traditional drug treatments for atrial fibrillation (AF). Through a systematic review and meta-analysis, it seeks to provide a theoretical basis for using clinical CA for patients with AF. METHODS: We searched through articles detailing randomly controlled trials (RCTs) that assessed the surgical effect of CA on the treatment of AF. These articles were published before January 31, 2000 in various English databases, including PubMed, Embase, Medline, Ovid, Springer, and Web of Sciences. The Cochrane Handbook for Systematic Reviews of Intervention 5.0.2 was adopted for the bias risk assessment, and Review Manager 5.3 software was used for the meta-analysis of the articles. RESULTS: A total of 2,098 patients drawn from 13 articles were included in the study. For patients in the experimental group (Exp. group), the meta-analysis showed an increase in the effects of clinical treatment [mean deviation (MD) =3.91; 95% confidence interval (CI), 3.15-4.85; Z=12.36; P<0.00001], an improvement in daily life function (MD =1.45; 95% CI, 1.03-1.87; Z=6.82; P<0.00001), a decrease in body weakness (MD =-2.84; 95% CI, -3.24 to -2.45; Z=14.16; P <0.00001), and an increase in quality of life score (MD =14.15; 95% CI, 7.24-21.05; Z=4.01; P<0.0001). The Exp. group also experienced a reduction in postoperative pain level (MD =-2.5; 95% CI, -3.11 to -1.89; Z=8.04; P<0.00001), reoccurrence of symptomatic AF (OR =0.27; 95% CI, 0.11-0.67; Z=2.82; P=0.005), rehospitalization (MD =0.15; 95% CI, 0.07-0.31; Z=5.11; P<0.00001), other arrhythmia (MD =0.33; 95% CI, 0.18-0.6; Z=3.62; P=0.0003), and pulmonary vein stenosis (PVS) (MD =0.32; 95% CI, 0.14-0.72; Z=2.74; P=0.006). However, in contrast to patients in the control group (Ctrl group), the 'bleeding' mentioned above showed no statistical difference. DISCUSSION: CA has a good postoperative clinical effect on AF patients, reducing incidences of pain, adverse reactions, and rehospitalization. For this reason, CA is a suitable treatment for AF patients who do not effectively respond to drug therapy.

Ghrelin attenuate cerebral microvascular leakage by regulating inflammation and apoptosis potentially via a p38 MAPK-JNK dependent pathway.

Ghrelin is a peptide hormone with strong anti-inflammatory properties. In fact, Ghrelin was reported to improve endothelial dysfunction caused by excessive fat. However, its role in preserving the integrity of brain microvascular, under conditions of lipid dysregulation and inflammation, is not known. The objective of this study is to characterize the role of Ghrelin in the protection of cerebral microvascular integrity, during atherosclerosis, and uncover its underlying molecular mechanism. Our results demonstrated that an atherosclerotic condition, brought on by a high fat diet (HFD), can produce massive increases in serum inflammatory factors, blood lipids, cerebral microvascular leakage, and activation of the p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) (p38 MAPK-JNK) pathway. It also produced significantly damaged pericytes morphology, resulting in pericyte decrease. Ghrelin treatment, on the other hand, protected against cerebral microvascular leakage and pericytes damage. Ghrelin effectively downregulated the expression of pro-inflammatory cytokines, and it also suppressed the p38 MAPK-JNK signaling pathway. Additionally, in isolated mouse cerebral microvascular pericytes, ox-LDL lead to increased apoptosis and secretion of inflammatory factors, along with an elevation in phosphorylated p38 MAPK-JNK proteins. Alternately, Ghrelin administration markedly lowered expression of inflammatory factors, suppressed the p38 MAPK-JNK signaling path, and halted cell apoptosis. However, pretreatment of Hesperetin, a p38 MAPK-JNK agonist, abrogated the Ghrelin-mediated suppression of inflammation and apoptosis in pericytes. Taken together, these results suggest that Ghrelin restored cerebral microvascular integrity and reduced vascular leakage in atherosclerosis mice, in part, by its regulation of inflammatory and apoptotic signaling pathways in pericytes.

Exercise enhances mitochondrial fission and mitophagy to improve myopathy following critical limb ischemia in elderly mice via the PGC1a/FNDC5/irisin pathway.

BACKGROUND: Elderly populations are susceptible to critical limb ischemia (CLI), but conventional treatments cannot significantly decrease amputation and mortality. Although exercise is an effective "non-pharmacological medicine" targeting mitochondria to improve skeletal muscle function, few studies have focused on the application of exercise in CLI. METHODS: Elderly male C57BL/6 mice (14 months old) were used to establish a CLI model to assess the effect of exercise on perfusion, performance recovery, apoptosis, mitochondrial function, and mitochondrial turnover in gastrocnemius muscle. The potential underlying mechanism mediated by PGC1a/FNDC5/irisin was confirmed in hypoxic and nutrient-deprived myotubes undergoing electrical pulse stimuli (EPS). RESULTS: Exercise significantly accelerated the perfusion recovery and exercise performance in ischemic limbs following CLI. Exercise improved the mitochondrial membrane potential and total ATP production and decreased apoptosis in the ischemic limbs. Exercise increased the formation of mitochondrial derived vesicle-like structures and decreased the mitochondrial length in the ischemic limbs, accompanied by upregulated PGC1a/FNDC5/irisin expression. In vitro, PGC1a/FNDC5/irisin downregulation decreased EPS-elevated PINK1, Parkin, DRP1, and LC3B mRNA levels. The irisin levels in the culture medium were correlated with the expression of mitochondrial fission and mitophagy markers in myotubes. CONCLUSION: Exercise enhanced mitochondrial fission and selective autophagy to promote the recovery of myopathy after CLI in elderly mice through the PGC1a/FNDC5/irisin pathway, supporting the efficacy of exercise therapy in elderly individuals with CLI and demonstrating the potential of targeting PGC1a/FNDC5/irisin as a new strategy for the treatment of CLI.

The Effect of MicroRNA-101 on Angiogenesis of Human Umbilical Vein Endothelial Cells during Hypoxia and in Mice with Myocardial Infarction.

BACKGROUND: Previous studies showed that recanalization and angiogenesis within the infarct region are of vital importance to the survival of myocardial cells during the treatment of acute myocardial infarction (AMI). METHODS: In this study, EdU cell proliferation assay, Transwell assay, scratch wound assay, and tube formation assay were used. Twelve bioinformatics analysis packages were used to predict the target genes of miR-101. Target genes were verified by luciferase reporter generation and assay, fluorescent quantitative PCR, and western blotting. Animal model and treatments were detected by M-mode echocardiography and immunofluorescent staining of CD31, Ki67, and α-SMA. RESULTS: AgomiR-101 significantly enhanced HUVEC proliferation, migration, and tube formation. A double-luciferase reporter assay revealed that the hsa-miR-101 mimic attenuated the activity of the EIF4E3'-UTR-wt type plasmid by 36%. The expression levels of HIF-1α and VEGF-A in the scrambled RNA group were significantly lower than those in the EIF4E3 siRNA and agomiR-101 groups. The left ventricular ejection fraction of the AMI+Adv-miR-101 group was significantly higher than that of the AMI+Adv-null and Sham+Adv-null groups. The proliferation of vessel cells in the peripheral infarcted myocardium was higher in the AMI+Adv-miR-101 group than that in the AMI+Adv-null and Sham+Adv-null groups. CONCLUSION: MiR-101 can promote angiogenesis in the region surrounding the myocardial infarction.

The relationships among the skeletal muscle mass index, cardiorespiratory fitness and the prevalence of coronary artery disease in the elderly population.

OBJECTIVE: Few studies have investigated the association between cardiorespiratory fitness (CRF) impairment and coronary artery disease (CAD) and the mediating mechanism. Therefore, we investigated the impact of skeletal muscle mass (SMM) on the relationship between CRF and coronary artery disease (CAD) in elderly people. METHODS: In this cross-sectional study, 109 elderly patients with coronary artery stenosis ≥50% were included in the CAD group, and 148 patients with coronary artery stenosis <50% were included as controls. Mediation analyses were performed to determine the role of the skeletal muscle index (SMI) in the relationship between CRF and the prevalence of CAD. A receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of CRF markers and the SMI. RESULTS: The oxygen pulse, VO2 max, and MET max were significantly associated with the SMI. In the multiple logistic regression analyses, the oxygen pulse and SMI were both independently correlated with the prevalence of CAD. The mediation analyses showed that the SMI affects the relationship between CRF markers (oxygen pulse, VO2 max, and MET max) and the prevalence of CAD. The receiver operating characteristic (ROC) curve analysis showed that when CRF and the SMI are considered together, the predictive power for CAD is stronger than that of the CRF alone. CONCLUSION: Enhancing CRF can facilitate improvement in SMM and decrease the prevalence of CAD in the elderly population. The addition of the SMI to CRF markers may increase the predictive value of CAD.

Serum sclerostin and adverse outcomes in elderly patients with stable coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: Recently, sclerostin, a bone-derived protein, has been shown to play a key role in atherosclerosis progression. However, few studies have investigated the influence of sclerostin on cardiovascular disease prognosis. We investigated the relationship between serum sclerostin levels and adverse outcomes in elderly patients with stable coronary artery disease (SCAD) who were undergoing percutaneous coronary intervention (PCI). METHODS: We enrolled 310 elderly SCAD patients who underwent PCI in this study and followed them 3 years. According to the median serum sclerostin levels, subjects were stratified into a low sclerostin (low scl) group (n = 144) and a high sclerostin (high scl) group (n = 166). Time-to-event analyses were performed with the Kaplan-Meier method. Associations between sclerostin levels and main adverse cardiovascular and cerebrovascular events (MACCEs) and mortality were evaluated by Cox multivariate regression analysis. The prognostic power of predictive models was verified by the concordance index and receiver operating characteristic curve analysis. RESULTS: The high scl group had a significantly higher MACCE-free rate and better survival than the low scl group. Serum sclerostin was an independent predictor and could improve the prognostic power for adverse outcomes. In addition, serum sclerostin levels were significantly associated with bone turnover markers, a lower presence of multivessel disease and a lower CCS angina class. CONCLUSIONS: Serum sclerostin is a prognostic parameter for predicting and intervening in the adverse outcomes of elderly SCAD patients undergoing PCI, which may be explained by its potential role in the bone-vascular axis.