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The canonical transient receptor potential channel (TRPC) proteins form Ca2+-permeable cation channels that are involved in various heart diseases. However, the roles of specific TRPC proteins in myocardial ischemia/reperfusion (I/R) injury remain poorly understood. We observed that TRPC1 and TRPC6 were highly expressed in the area at risk (AAR) in a coronary artery ligation induced I/R model. Trpc1 −/− mice exhibited improved cardiac function, lower serum Troponin T and serum creatine kinase level, smaller infarct volume, less fibrotic scars, and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6 −/− mice. Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury. Furthermore, Trpc1 deficiency protected adult mouse ventricular myocytes (AMVMs) and HL-1 cells from death during hypoxia/reoxygenation (H/R) injury. RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species (ROS) generation in Trpc1 −/− cardiomyocytes. Among these genes, oxoglutarate dehydrogenase-like (Ogdhl) was markedly downregulated. Moreover, Trpc1 deficiency impaired the calcineurin (CaN)/nuclear factor-kappa B (NF-κB) signaling pathway in AMVMs. Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions. Chromatin immunoprecipitation assays confirmed NF-κB binding to the Ogdhl promoter. The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF - κB and Ogdhl in cardiomyocytes. In conclusion, our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R, leading to increased Ca2+ influx into associated cardiomyocytes. Subsequently, this upregulates Ogdhl expression through the CaN/NF-κB signaling pathway, ultimately exacerbating ROS production and aggravating myocardial I/R injury. [Display omitted] • Trpc1 knockout ameliorates myocardial I/R injury. • Trpc1 deficiency attenuates the ROS upregulation post myocardial I/R injury. • Trpc1 deficiency reduces ROS generation via downregulating α-ketoglutarate dehydrogenase. [ABSTRACT FROM AUTHOR]

Aims Endothelial progenitor cell (EPC) dysfunction underlies a critical risk factor in diabetic vascular complications due to function defect in restoring endothelium injury. Crocetin has attracted increasing attention in several vascular-related diseases. In present study, we aimed to explore the role of crocetin in diabetic EPC dysfunction. Main methods EPCs were isolated from bone marrow in diabetic mice and identified using the fluorescence staining and flow cytometry. After exposure to various doses of crocetin, cell viability was detected by MTT assy. Then, colony formation, lactate dehydrogenase (LDH) release, cell apoptosis and caspase-3 activity were assessed. The underlying mechanism was also investigated by western blotting. Key findings EPCs from diabetic mice exhibited dysfunction under hyperglycemia condition. Interestingly, crocetin treatment alleviated the impairment in diabetic EPC proliferation and colony formation. Simultaneously, the increases in LDH release, cell apoptosis and caspase-3 activity were also restrained following crocetin stimulation. Additionally, EPC migration response to SDF-1 was also impaired under diabetic condition, which was partly restored by crocetin. Mechanism analysis manifested that administration with crocetin repaired the damage in the activation of PI3K/AKT-eNOS pathway and NO production, but attenuated ROS elevation in diabetic EPCs. Importantly, preconditioning with antagonist of LY294002 (for PI3K/AKT) or N G -monomethyl- l -arginine (for eNOS) antagonized the beneficial effect of crocetin on diabetic EPC dysfunction. Significance These data corroborated that crocetin could restore the dysfunction of diabetic EPCs by enhancing NO bioavailability via regulation of PI3K/AKT-eNOS and ROS pathways. Therefore, this research supports a potential promising therapeutic aspect for diabetic patients. [ABSTRACT FROM AUTHOR]

A lipidated polysaccharide, HDPS-2II, was isolated from the dried larva of Holotrichia diomphalia , which is used in traditional Chinese medicine. The molecular weight of HDPS-2II was 5.9 kDa, which contained a polysaccharide backbone of →4)-β-Man p -(1 → 4,6)-β-Man p -(1 → [6)-α-Glc p -(1] n → 6)-α-Glc p → with the side chain α-Glc p -(6 → 1)-α-Glc p -(6 → linked to the C-4 of β-1,4,6-Man p and four types of lipid chains including 4-(4-methyl-2-(methylamino)pentanamido)pentanoic acid, 5-(3-(tert-butyl)phenoxy)hexan-2-ol, N-(3-methyl-5-oxopentan-2-yl)palmitamide, and N-(5-amino-3-methyl-5-oxopentan-2-yl)stearamide. The lipid chains were linked to C-1 of terminal α-1,6-Glc p in carbohydrate chain through diacyl-glycerol. HDPS-2II exhibited DNA protective effects and antioxidative activity on H 2 O 2 - or adriamycin (ADM)-induced Chinese hamster lung cells. Furthermore, HDPS-2II significantly ameliorated chromosome aberrations and the accumulation of reactive oxygen species (ROS), reduced γ-H2AX signaling and the expressions of NADPH oxidase (NOX)2, NOX4, P22phox, and P47phox in ADM-induced cardiomyocytes. Mechanistically, HDPS-2II suppressed ADM-induced up-regulation of NOX2 and NOX4 in cardiomyocytes, but not in NOX2 or NOX4 knocked-down cardiomyocytes, indicating that HDPS-2II could relieve intracellular DNA damage by regulating NOX2/NOX4 signaling. These findings demonstrate that HDPS-2II is a new potential DNA protective agent. [ABSTRACT FROM AUTHOR]

The construction of advanced systems that can accurately detect neuron-specific enolase (NSE) is critical to the rapid diagnosis of small cell lung cancer (SCLC). Herein, a luminol-based electrochemiluminescence (ECL) biosensor enhanced by reactive oxygen species (ROS) is proposed to perform the ultrasensitive detection of NSE. D-Fe 2 O 3 @Pt, synthesized as a signal indicator, was combined with luminol to significantly shorten its electron transfer pathway. Its peroxidase activity catalyzed the decomposition of H 2 O 2 to generate a large amount of •OH, thus considerably increasing the ECL signal of the luminol–H 2 O 2 system. CePO 4 /CeO 2 heterostructures with improved surface-active areas were then employed as sensing substrates. The platform enabled the accelerated generation of O 2 •− through enriched Ce4+/Ce3+ redox pairs, thereby amplifying the strength of the response of the foundation. Through integrated dual ROS amplification, the proposed sandwich ECL immunosensor configuration achieved sensitive detection in the detection range of 76 fg/mL – 100 ng/mL, with a detection limit of 72.4 fg/mL. Furthermore, the sensor exhibited high selectivity for the determination of NSE in human serum. Overall, this study serves as an important reference for integrating ROS and enzymatic strategies in ECL research to achieve accurate, sensitive, and highly selective detection of a target. [ABSTRACT FROM AUTHOR]

Peach fruit deteriorates and senesces quickly during storage at ambient temperature. Research confirms that melatonin (MT) is involved in plant senescence. However, little information is available on the effects of MT on postharvest senescence. In this study, two cultivars of peach fruit ‘Shahong’ and ‘Qinmi’ were treated with MT at 0.1 mmol L −1 and then stored at ambient temperature (25–28 °C)for 7 days. The results showed that MT treatment effectively slowed process of senescence in both peach cultivars, as indicated by reduced weight loss, decay incidence and respiration rate as well as maintained firmness, total soluble solids and ascorbic acid contents. MT treatment significantly enhanced the activities of superoxide dismutase, catalase, peroxidase and ascorbate peroxidase in both cultivars, but decreased the activity of lipoxygenase, levels of superoxide anion and hydrogen peroxide, and malondialdehyde content. These results indicate that the activation of antioxidant enzymes to scavenge superoxide anion and hydrogen peroxide by MT treatment was associated with the maintenance of membrane integrity, which might be a part of the mechanism implicated in delay of senescence in peach fruit. [ABSTRACT FROM AUTHOR]

Biocompatible nitrogen-doped hydrazide-conjugated carbon dots (NHCDs) as an anodic luminophores with low excitation potential were equipped with an efficient multiple signal-amplification strategy for electrochemiluminescence (ECL) trace bioanalysis. To promote the ECL emission of NHCDs-H 2 O 2 system, gold nanoparticles (Au NPs) functionalized tin oxide nanocrystals (Au@SnO 2 NCs) were adopted to anchor large amount of NHCDs, the formed NHCDs-Au@SnO 2 NCs could conjugate with detection antibody as the signal label. Moreover, 3,4,9,10-perylenetetracarboxylic acid (PTCA) molecules were immobilized on the flower-like microsphere (PTCA@ZnCo 2 O 4 /ZnO) nanocomposites to fabricate as an electro-active sensing substrate to incubate the capture antibody, which could efficiently accelerate the generation of reactive oxygen species (OH · /O 2 ·- ) through electrocatalytic excitation and co-reaction acceleration. Integrating with the sandwich-type sensing model, an ECL immunosensor was established to detect biomarkers of squamous cell carcinomas named cytokeratin 19 fragments (cyfra21–1). Combining with the synergistic signal-amplification induced by the Au@SnO 2 NCs, PTCA, and ZnCo 2 O 4 /ZnO nanocomposites, the developed immunosensor performed detection range from 0.09 pg/mL to 100 ng/mL with a detection limit of 34.38 fg/mL. The results showcased the great potential of this sensing strategy for real sample analysis of biomarker with reliable stability, selectivity and repeatability. • Flower-like PTCA-modified ZnCo 2 O 4 /ZnO was synthesized by hydrothermal method. • PTCA-modified ZnCo 2 O 4 /ZnO was demonstrated that can efficiently achieve electrocatalytic excitation and catalyze the ROSs production to amplify the ECL signal. • Au@SnO 2 NCs was utilized to construct highly efficient catalytic nanocarriers. • Signal multiple-amplification strategy was built to improve sensitivity. • The established immunosensor exhibited low detection limit of 34.38 fg·mL-1 for CYFRA21-1. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Owing to the limitations in the current therapeutic strategies for treating HCC, development of novel chemotherapeutic drugs is urgently needed. In the present study, we found that QQM, a newly-synthesized quinolinylmethyl substituted ethylenediamine compound, exhibited anti-HCC effects both in vitro and in vivo. QQM inhibited HCC cell growth and induced G0/G1-phase cell cycle arrest and apoptosis in a dose-dependent manner. Our results showed that QQM acted by significantly increasing intracellular reactive oxygen species in HCC cells, which led to cell apoptosis and growth inhibition. Furthermore, QQM treatment resulted in an accumulation of reactive nitric oxide (NO) in HCC cells, and introduction of a NO scavenger, carboxy-PTIO, largely attenuated QQM-induced cytotoxicity. Finally, we found that QQM inhibited growth and induced apoptosis of HCC xenograft tumors in vivo. Taken together, our results indicated that QQM exerted anti-HCC effects by inducing reactive oxygen species and NO accumulation in HCC cells. Thus, QQM exhibits the qualities of a novel, promising anti-tumor candidate for the treatment of HCC. Image 1 [ABSTRACT FROM AUTHOR]

Development of a simple, cost-effective and sensitive biosensing strategy is highly desirable to advance the applications in Alzheimer's disease diagnosis. In this paper, we present a simple, label-free and signal-on electrochemiluminescence (ECL) aptasensor for the detection of amyloid-beta (Aβ) peptide using luminol as ECL emitter and in-situ generated reactive oxygen species (ROS) as coreactant via catalytic reaction between Cu2+-Aβ and the dissolved O 2 in the presence of ascorbic acid (AA). Aβ 16 , the binding site of Cu2+ in the monomeric full-length Aβ, was used as a model in present study. As a result, this signal-on ECL aptasensor has exhibited favorable analytical performance for Aβ 16 monomer with a linear range of 1.0 × 10-13 mol/L-1.0 × 10-8 mol/L and a limit of detection of 3.5 × 10-14 mol/L (S/N=3). Furthermore, the proposed biosensor was also able to detect the full length Aβ 40 not only in the phosphate buffer saline (PBS) solution but also in human serum. The presented biosensor represents a promising, simple, turn-on and label-free diagnostic tool for blood analysis. • A simple, label-free and signal-on ECL aptasensor for the detection of Aβ peptide was development. • The aptasensor can monitor the aggregation process of Aβ 16 monomer accelerated by Cu2+. • The proposed biosensor was able to detect the full length Aβ 40 not only in the PBS solution but also in human serum. [ABSTRACT FROM AUTHOR]