Animal models of heart failure with preserved ejection fraction (HFpEF): from metabolic pathobiology to drug discovery.

Heart failure (HF) with preserved ejection fraction (HFpEF) is currently a preeminent challenge for cardiovascular medicine. It has a poor prognosis, increasing mortality, and is escalating in prevalence worldwide. Despite accounting for over 50% of all HF patients, the mechanistic underpinnings driving HFpEF are poorly understood, thus impeding the discovery and development of mechanism-based therapies. HFpEF is a disease syndrome driven by diverse comorbidities, including hypertension, diabetes and obesity, pulmonary hypertension, aging, and atrial fibrillation. There is a lack of high-fidelity animal models that faithfully recapitulate the HFpEF phenotype, owing primarily to the disease heterogeneity, which has hampered our understanding of the complex pathophysiology of HFpEF. This review provides an updated overview of the currently available animal models of HFpEF and discusses their characteristics from the perspective of energy metabolism. Interventional strategies for efficiently utilizing energy substrates in preclinical HFpEF models are also discussed.

Molecular Engineering of Aromatic Imides for Organic Secondary Batteries.

Aromatic imides are a class of attractive organic materials with inherently electroactive groups and large π electron-deficient scaffolds, which hold potential as electrode materials for organic secondary batteries (OSBs). However, the undecorated aromatic imides are usually plagued by low capacity, high solubility in electrolyte, and poor electronic/ionic conductivity. Molecular engineering has been demonstrated to be an effective strategy to address unsatisfying characteristics of the aromatic imides, thereby expanding their scope for applications in OSBs. In this review, the recent research progress in modulation of the capacity, dissolution, and electronic/ionic conductivity of aromatic imides for organic lithium batteries, organic sodium batteries, and redox flow batteries are summarized. In addition, the challenge and prospective of aromatic imides in organic secondary battery applications are also discussed.

The Clinical Significance of Serum MASP-2 and IDH1 in the Early Diagnosis of Non-Small Cell Lung Cancer.

BACKGROUND: The lack of effective means for the early diagnosis of non-small cell lung cancer (NSCLC) is the leading cause of the high mortality of NSCLC. This study aims to evaluate the clinical significance of serum mannan-binding lectin associated serine protease (MASP)-2 and isocitrate dehydrogenase 1 (IDH1) in the early diagnosis of NSCLC. METHODS: The serum levels of MASP-2 and IDH1 were detected in 139 NSCLC patients, 46 patients with benign lung diseases and 61 healthy controls, using an enzyme linked immunosorbent method. The diagnostic significance in NSCLC of the two tumor markers were analyzed by receiver operating characteristic (ROC) curves. In addition, we compared the two markers with the current commonly used tumor marker cytokeratin 19 fragment (Cy¬fra21-1). RESULTS: The serum levels of MASP-2 and IDH1 in the NSCLC patients were significantly higher than those of healthy controls and patients with benign lung diseases. The differences were statistically significant (p < 0.01). The combined sensitivity of MASP-2, IDH1, and Cyfra21-1 in the NSCLC was 68.3%, which was significantly higher than that of the single tumor marker (p < 0.01). The sensitivities of MASP-2 and IDH1 in detecting early NSCLC (stage I and stage II) were 39.0% and 41.5%, which were significantly higher than that of Cyfra21-1 (p < 0.05). The area under the ROC curves (AUCs) of MASP-2 and IDH1 in the diagnosis of NSCLC were 0.621, and 0.840, which were higher than that of Cyfra21-1 (AUC = 0.606). CONCLUSIONS: Serum MASP-2 and IDH1 may be used as potential tumor markers for the auxiliary diagnosis and early diagnosis of NSCLC.

Prognostic Significance of Serum miR-22, miR-125b, and miR-15b in Non-Small Cell Lung Cancer Patients.

BACKGROUND: Studies have shown that miRNA (miR) can be stably detected in serum, and aberrant expression of various miRNAs has shown diagnostic value in non-small cell lung cancer (NSCLC) patients. However, the role of miRNA in the context of prognosis has not been extensively investigated. Our previous study reported that miR-22, miR-125b, and miR-15b in serum had potential for use as tumor markers for auxiliary diagnosing of NSCLC. Therefore, the objective of this study was to detect the levels of miR-22, miR-125b, and miR-15b in serum from NSCLC patients and explore the potential prognostic significance of the three selected miRNAs. METHODS: The relative expression of miR-22, miR-125b, and miR-15b in 74 patients with advanced NSCLC in pre- and post-chemotherapy were detected by real-time quantitative polymerase chain reaction. RESULTS: Serum level of miR-125b significantly decreased after chemotherapy (p < 0.05) and the levels of miR-15b significantly increased (p < 0.01), while there was no change in the level of serum miR-22 (Z = 0.716, p > 0.05). Compared with pre-chemotherapy, serum miR-125b expression in advanced NSCLC patients of responders (CR + PR) were significantly decreased post-chemotherapy (p < 0.05); serum miR-15b expression in advanced NSCLC patients of responders (CR + PR) were increased (p < 0.01). The chemotherapy sensitivity of advanced NSCLC patients with high expression of miR-125b was lower than that of NSCLC patients with low expression (p < 0.05). The chemotherapy sensitivity of advanced NSCLC patients with high expression of miR-15b was higher than that of NSCLC patients with low expression (p < 0.05). High levels of serum miR-125b and low levels of serum miR-15b were related to poor overall survival (p < 0.05). CONCLUSIONS: The serum levels of miR-125b and miR-15b in advanced NSCLC patients were changed pre- and post-chemotherapy and these changes were associated with chemotherapeutic response. Serum miR-125b and miR-15b have certain potential clinical value for chemotherapeutic response in advanced NSCLC. The serum levels of miR-125b and miR-15b in patients with advanced NSCLC before treatment may be used to estimate the overall survival.

Significance of Serum MicroRNAs in the Auxiliary Diagnosis of Non-Small Cell Lung Cancer.

BACKGROUND: The lack of effective means for the early diagnosis of non-small cell lung cancer (NSCLC) is the leading cause of the high mortality associated with this form of lung cancer. This study aims to explore the potential significance of serum miRNA in the auxiliary diagnosis of NSCLC. METHODS: The relative serum levels of 10 miRNAs in 120 patients with NSCLC, 45 patients with benign lung diseases, and 45 healthy controls were detected using real-time quantitative polymerase chain reaction (PCR). The receiver operating characteristic (ROC) curves were then used to analyze the significance of the expression of these 10 miRNAs in the diagnosis of NSCLC, as well as to compare them with the current commonly used tumor marker carcinoembryonic antigen (CEA). RESULTS: The serum levels of miR-125b and miR-22 in the NSCLC patients were significantly higher than those in the other two groups (p < 0.05), but the serum expression of miR-15b in the NSCLC patients was significantly lower than that in the other two groups (p < 0.01). The sensitivities of serum miR-22 and miR-15b in detecting early NSCLC (stage I + II) were significantly higher than that of CEA (p < 0.05). Area under the curves (AUCs) of serum miR-22, miR-125b, and miR-15b in the diagnosis of NSCLC were 0.725, 0.704, and 0.619, respectively, and the diagnostic significance of these three serum miRNAs for NSCLC was higher than that of serum CEA (AUC = 0.594). CONCLUSIONS: Serum miRNAs have potential as NSCLC-screening tumor markers, and serum miR-22 and miR15b might be used as reference indexes for the early diagnosis of NSCLC in the future.

Reduction of Serum Cytokeratin-3A9 is Associated with Chemotherapeutic Response in Patients with Non-Small Cell Lung Cancer.

BACKGROUND: Many tumor markers have been analyzed for applications in diagnosis, prognosis, and monitoring of cancer. Currently chemotherapy is routinely performed for patients with non-small cell lung cancer (NSCLC). The purpose of this study was to examine the serum tumor biomarker of cytokeratin (CK)-3A9 level in patients with NSCLC and its potential correlation with chemotherapeutic response. METHODS: The serum samples of 196 NSCLC patients, 84 healthy controls, and 87 benign lung disease patients were provided for measurement of CK-3A9 and carcinoembryonic antigen (CEA). Serum CK-3A9 concentration was examined using a chemoluminescent method. The potential correlation between serum CK18-3A9 concentration and chemotherapeutic response was analyzed in 124 patients with advanced NSCLC (stages III and IV). RESULTS: The serum CK-3A9 levels in NSCLC patients pre-chemotherapy were significantly higher than those of healthy controls and benign lung disease patients (p < 0.01). CK-3A9 was related to Union for International Cancer Control (UICC) stages (p < 0.01) and histological classification (p < 0.05), but not related to age, gender, smoking status, and chemotherapy regimen (all p > 0.05). The testing results of serum CK-3A9 levels showed a higher sensitivity than that for CEA (48.2% and 39.5%, respectively). The chemotherapeutic response in the 124 patients with advanced NSCLC included 0 complete response (CR), 50 partial response (PR), 65 no change (NC), and 9 progression disease (PD). Post-chemotherapy CK-3A9 levels were significantly decreased compared to pre-chemotherapy (p < 0.05). The serum CK-3A9 levels in patients who achieved PR declined significantly compared to those who did not respond (SD + PD) after 2 cycles chemotherapy (p < 0.05). CONCLUSIONS: CK-3A9 appeared to be a new biomarker for reliable, cost-effective prediction of the efficacy of chemotherapy in patients with advanced NSCLC, although the results should be confirmed in larger studies.

The clinical value of new tumor biomarker cytokeratin 2G2 detection in non-small cell lung cancer patients.

BACKGROUND: Many tumor markers are analyzed for usefulness in diagnosis, prognosis, and monitoring. The purpose of this study was to evaluate a new type of tumor biomarker, cytokeratin (CK)-2G2, in serum for the early diagnosis, confirmative diagnosis as well as assessment of treatments of non-small cell lung cancer (NSCLC). METHODS: Use a chemiluminescent method to examine the serum CK-2G2 levels in 100 patients with non-malignant lung diseases and 100 cases from the healthy population, as well as 124 cases of NSCLC patients prior to chemotherapy, after one course of treatment and after two courses of treatment. RESULTS: The average levels of CK-2G2 in the serum of NSCLC patients was found to be significantly higher than that of the group of non-malignant patients as well as the healthy control group (p < 0.01). It was further observed that CK-2G2 is markedly higher in squamous-cell carcinoma than in adenocarcinoma (p < 0.05) whereas CK-2G2 was found to be higher in stages III and IV than stages I and II (p < 0.05) and CK-2G2 is markedly higher in large tumor size (> 3cm) than in small tumor size (< or = 3cm) (p < 0.05). Serum CK-2G2 levels for patients with cancer progression were found to increase after two courses of chemotherapy (p < 0.01) whereas patients with stabilized tumorigenesis or tumor regression showed a significant trend of CK-2G2 decrease (p < 0.01). CONCLUSIONS: Detection of the new tumor biomarker CK-2G2 has certain clinical values for early diagnosis, verification of diagnosis as well as classification of patients. Thus it is warranted that CK-2G2 be widely deployed as a new type of cost effective parameter for evaluating efficacy of chemotherapy of NSCLC.