Long non-coding RNA ZFAS1 is down-regulated in sepsis. However, whether ZFAS1 participates in sepsis-induced cardiomyopathy (SIC) remains largely unknown. LPS injection to rats was used to establish ...an in vivo sepsis model, while LPS stimulation with H9C2 cell was used to mimic an in vitro sepsis-induced myocardial injury model. Western blots and quantitative RT-PCR were performed to evaluate protein and mRNA levels, respectively. ELISA was conducted to determine cytokine levels in supernatant. Flow cytometry was used to test apoptosis. Dual-luciferase assay was performed to validate binding between ZFAS1 and miR-34b-5p, miR-34b-5p and SIRT1. Our data revealed that ZFAS1 and SIRT1 were down-regulated, while miR-34b-5p was up-regulated in LPS-induced H9C2 cells. Inhibition of miR-34b-5p or overexpression of ZFAS1 alleviated inflammatory response and cell apoptosis in LPS-stimulated H9C2 cells. A mechanism study revealed that ZFAS1 sponged miR-34b-5p and thus elevated expression of SIRT1, which was prohibited by miR-34b-5p. ZFAS1 alleviated inflammatory response and cell apoptosis in LPS-stimulated H9C2 cells via the miR-34b-5p/SIRT1 axis, providing novel potential therapeutic targets for SIC.
Chronic kidney disease (CKD) results in significant dyslipidemia and profound changes in lipid and lipoprotein metabolism. The associated dyslipidemia, in turn, contributes to progression of CKD and ...its cardiovascular complications. To gain an in-depth insight into the disorders of lipid metabolism in advanced CKD, we applied UPLC-HDMS-based lipidomics to measure serum lipid metabolites in 180 patients with advanced CKD and 120 age-matched healthy controls. We found significant increases in the levels of total free fatty acids, glycerolipids, and glycerophospholipids in patients with CKD. The levels of free fatty acids, glycerolipids, and glycerophospholipids directly correlated with the level of serum triglyceride and inversely correlated with the levels of total cholesterol and eGFR. A total of 126 lipid species were identified from positive and negative ion modes. Out of 126, 113 identified lipid species were significantly altered in patients with CKD based on the adjusted FDR method. These results pointed to profound disturbance of fatty acid and triglyceride metabolisms in patients with CKD. Logistic regression analysis showed strong correlations between serum methyl hexadecanoic acid, LPC(24:1), 3-oxooctadecanoic acid, and PC(20:2/24:1) levels with eGFR and serum creatinine levels (R > 0.8758). In conclusion, application of UPLC-HDMS-based lipidomic technique revealed profound changes in lipid metabolites in patients with CKD. The observed increases in serum total fatty acids, glycerolipids, and glycerophospholipids levels directly correlated with increased serum triglyceride level and inversely correlated with the eGFR and triglyceride levels.
Abstract
Background
Ferroptosis is a new type of nonapoptotic cell death model that was closely related to reactive oxygen species (ROS) accumulation. Seawater drowning-induced acute lung injury ...(ALI) which is caused by severe oxidative stress injury, has been a major cause of accidental death worldwide. The latest evidences indicate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) suppress ferroptosis and maintain cellular redox balance. Here, we test the hypothesis that activation of Nrf2 pathway attenuates seawater drowning-induced ALI via inhibiting ferroptosis.
Methods
we performed studies using Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the potential roles of Nrf2 on seawater drowning-induced ALI and the underlying mechanisms.
Results
Our data shows that Nrf2 activator dimethyl fumarate could increase cell viability, reduced the levels of intracellular ROS and lipid ROS, prevented glutathione depletion and lipid peroxide accumulation, increased
FTH1
and
GPX4
mRNA expression, and maintained mitochondrial membrane potential in MLE-12 cells. However, ML385 promoted cell death and lipid ROS production in MLE-12 cells. Furthermore, the lung injury became more aggravated in the Nrf2-knockout mice than that in WT mice after seawater drowning.
Conclusions
These results suggested that Nrf2 can inhibit ferroptosis and therefore alleviate ALI induced by seawater drowning. The effectiveness of ferroptosis inhibition by Nrf2 provides a novel therapeutic target for seawater drowning-induced ALI.
Ischemia/reperfusion (IR) injury contributes to disability and mortality worldwide. Due to the complicated mechanisms and lack of proper therapeutic targets, few interventions are available that ...specifically target the pathogenesis of IR injury. Regulated cell death (RCD) of endothelial and parenchymal cells is recognized as the promising intervening target. Recent advances in IR injury suggest that small molecules exhibit beneficial effects on various RCD against IR injury, including apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis, and parthanatos. Here, we describe the mechanisms behind these novel promising therapeutic targets and explain the machinery powering the small molecules. These small molecules exert protection by targeting endothelial or parenchymal cells to alleviate IR injury. Therapies of the ideal combination of small molecules targeting multiple cell types have shown potent synergetic therapeutic effects, laying the foundation for novel strategies to attenuate IR injury.
Display omitted
•This review summarized the updated studies on tea (Camellia sinensis L.) flower.•The genes involved in the development of tea flower are presented.•Numerous functional constituents ...with their various health benefits are summarized.•Tea flower aqueous extracts are safe to animals.•Possible food and medical uses of tea flowers is warranted.
The flower of tea (Camellia sinensis L.) plant has been paid an increasing attention in the last twenty years, since it was found that tea flowers contained representative constituents similar to those of tea leaves, such as catechins, caffeine and amino acids. Tea flower is theoretically valuable although it has been considered as an industrial waste over a long period of time. This review summarizes the research findings conducted until now on physiological genetics, chemical composition, health benefits and toxicology of tea flowers, aiming to foresee their future applications. A lot of genes are involved in flower development and the synthesis and transmission of various chemicals in tea flowers. The chemical composition of tea flower consists mainly of catechins, polysaccharides, proteins, amino acids and saponins and thus tea flower possesses various health benefits such as antioxidant, anti-inflammatory, immunostimulating, antitumor, hypoglycemic, anti-obesity and anti-allergic activities. Moreover, tea flower contains a protease that can elevate the free amino acids content in the tea infusion by almost two folds. More importantly, the enzymatic activity of the protease is much higher than that of the commercially available proteases. Additionally, aqueous extracts of tea flower are demonstrated to safe to animals. Thus, the potential uses of tea flowers in food and medical fields are warranted.
Triple-negative breast cancer (TNBC) was a particularly aggressive subtype of breast cancer associated with poor prognosis. This retrospective study was conducted to investigate the clinical ...features, prognostic factors, and benefits of surgery of patients with TNBC.
From 2010 to 2015, 33654 female patients with TNBC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were randomly divided into the training and validation cohorts. Univariate and multivariable cox regression were performed to identify prognostic factors, based on which a nomogram was constructed. Validation of the nomogram was assessed by concordance index (c-index) and calibration curves. Survival curves were plotted according to metastatic burdens and risk groups differentiated by nomogram.
Patients of younger age (<65 years old), white race, married status, lower grade, lower TNM stage and primary tumor surgery tended to have better outcome. The C-index and calibration curves displayed high discrimination in the training and validation sets (C-index 0.794 and 0.793, respectively), indicating suitable external performance of the nomogram model. Patients of bone-only metastases as well as bone and liver metastases showed superior cancer-specific survival (CSS) time if surgery of primary tumor was performed. Besides, patients of all risk groups showed better CSS when receiving surgery.
This study provided population-based prognostic analysis in patients with TNBC and constructed a predicting nomogram with a robust discrimination. The findings of potential benefit of surgery to CSS would shed some lights on the treatment tactics of patients with TNBC.
This study aimed to investigate the prognostic factors of patients with TNBC. Thirty-three thousand six hundred fifty-fourth female patients from SEER database were divided into the training and validation cohorts for predictive model construction and validation. The constructed nomogram based on 6 factors was proved a robust discrimination, which could provide guidance on the personalized therapy.
In the human body, carboxylesterases (CEs) play crucial roles in xenobiotic metabolism and lipid homeostasis. But abnormal expression of CEs is highly associated with some diseases, such as ...hyperlipidemia, diabetes, and liver cancer. Therefore, it is of great importance to develop an efficient tool for the accurate detection of CEs in living organisms. Herein, an innovative near-infrared (NIR) fluorescent probe, TTAP−AB, was designed for CE detection based on the aggregation-induced emission (AIE) mechanism. This probe exhibits rapid response (2 min), excellent sensitivity (limit of detection = 8.14 × 10−6 U/mL), and high selectivity to CEs. Additionally, owing to its good biocompatibility, the TTAP−AB probe enables the monitoring of dynamic changes in CE levels under drug-induced modulation in living cells and zebrafish. More importantly, the TTAP−AB probe was successfully employed to image liver tumors and assist in tumor resection through the real-time monitoring of CEs, indicating that TTAP−AB is promising to guide liver cancer surgery. Therefore, the TTAP−AB probe can not only enrich the strategies for CE detection in biological systems but also has great potential for some clinical imaging applications, including medical diagnosis, preclinical research, and imaging-guided surgery.
Hypochlorite (ClO−) and viscosity both affect the physiological state of mitochondria, and their abnormal levels are closely related to many common diseases. Therefore, it is vitally important to ...develop mitochondria-targeting fluorescent probes for the dual sensing of ClO− and viscosity. Herein, we have explored a new fluorescent probe, XTAP–Bn, which responds sensitively to ClO− and viscosity with off–on fluorescence changes at 558 and 765 nm, respectively. Because the emission wavelength gap is more than 200 nm, XTAP–Bn can effectively eliminate the signal crosstalk during the simultaneous detection of ClO− and viscosity. In addition, XTAP–Bn has several advantages, including high selectivity, rapid response, good water solubility, low cytotoxicity, and excellent mitochondrial-targeting ability. More importantly, probe XTAP–Bn is successfully employed to monitor the dynamic change in ClO− and viscosity levels in the mitochondria of living cells and zebrafish. This study not only provides a reliable tool for identifying mitochondrial dysfunction but also offers a potential approach for the early diagnosis of mitochondrial-related diseases.
Transforming growth factor-β1 (TGF-β1) is considered as a crucial mediator in tissue fibrosis and causes tissue scarring largely by activating its downstream small mother against decapentaplegic ...(Smad) signaling. Different TGF-β signalings play different roles in fibrogenesis. TGF-β1 directly activates Smad signaling which triggers pro-fibrotic gene overexpression. Excessive studies have demonstrated that dysregulation of TGF-β1/Smad pathway was an important pathogenic mechanism in tissue fibrosis. Smad2 and Smad3 are the two major downstream regulator that promote TGF-β1-mediated tissue fibrosis, while Smad7 serves as a negative feedback regulator of TGF-β1/Smad pathway thereby protects against TGF-β1-mediated fibrosis. This review presents an overview of the molecular mechanisms of TGF-β/Smad signaling pathway in renal, hepatic, pulmonary and cardiac fibrosis, followed by an in-depth discussion of their molecular mechanisms of intervention effects both in vitro and in vivo. The role of TGF-β/Smad signaling pathway in tumor or cancer is also discussed. Additionally, the current advances also highlight targeting TGF-β/Smad signaling pathway for the prevention of tissue fibrosis. The review reveals comprehensive pathophysiological mechanisms of tissue fibrosis. Particular challenges are presented and placed within the context of future applications against tissue fibrosis.
•TGF-β1 is considered as a crucial mediator in tissue fibrosis.•TGF-β1/Smad pathway is an important pathogenic mechanism in tissue fibrosis.•TGF-β/Smad pathway in cardiac, hepatic, pulmonary and renal fibrosis are discussed.•Targeting TGF-β/Smad pathway is an important therapeutic strategy for fibrosis.
•We conducted bibliometric analysis on emergy from 1996 to 2014.•Citespace software was used to visualize the literature data.•The trend and publication patterns of existing emergy literature were ...reported.•The intellectual core of emergy research was identified through citation analysis.
A bibliometric approach, along with Citespace software, was used to quantitatively and visually evaluate global scientific research on emergy from 1996 to 2014. 637 publications – in accordance with the search criteria from the Science Citation Index Expanded (SCI-Expanded) and Social Science Citation Index (SSCI) of the Web of Science database – were statistically analyzed. The assessments on document type and language, publication year, authorship, subject categories and journals, countries/territories and institutions, most-frequently cited publications and author keywords were conducted with respect to seven categories. The amount of emergy publications per year has sharply increased in recent years. The most productive author was S. Ulgiati with 50 articles, who was also one of the most frequently cited publication authors. China produced 35.95% of all pertinent publications followed by the USA with 25.59% and Italy with 21.66%. Ecological Modeling, Ecological Engineering and Ecological Indicators were the three most common journals in this field. By synthetically analyzing the keywords, the dominant hot spots of emergy research could be concluded as “energy”, “sustainability”, “transformity”, and “indicators”.
PDF
