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Objective: To investigate the independent effects of irisin on insulin resistance (IR) in ovary of polycystic ovary syndrome (PCOS) and explore possible pathways. Methods: We established PCOS medel using Poretsky L's method, then PCOS rats were randomly divided into model group (M) and irisin group (I), and normal rats (N) were used as the control. Then rats in the group I were injected with recombinant irisin. Then the levels of circulating fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of IR (HOMA‐IR) and PI3K/AKT and MAPK/ERK pathways in each group were observed, as well as the effects of irisin on the levels of circulating HOMA‐IR and PI3K/AKT and MAPK/ERK pathways in ovary of PCOS rats were evaluated. Results: Compared with normal group, levels of FBG, FINS, and HOMA‐IR of model group were significantly increased (p < 0.001, p < 0.001, and p < 0.001, respectively), levels of average optical density by IHC of p‐PI3K, PI3K, p‐AKT, and AKT (p = 0.015, p = 0.010, p = 0.005, and p = 0.009, respectively) and levels of mRNA concentration of PI3K and AKT (p = 0.001, and p = 0.005, respectively) were decreased, while the levels of average optical density of p‐ERK, ERK (p = 0.011, and p = 0.013, respectively) and level of mRNA concentration of ERK (p < 0.001) were increased in ovary. After irisin intervention, compared with model group, levels of FBG, FINS, and HOMA‐IR of rats in irisin group were significantly decreased (p = 0.001, p < 0.001, and p < 0.001, respectively), levels of average optical density by IHC of p‐PI3K, PI3K, p‐AKT, and AKT (p = 0.030, p = 0.024, p = 0.012, and p = 0.025, respectively) and levels of mRNA concentration of PI3K and AKT (p = 0.002, and p = 0.003, respectively) were significantly increased, while the levels of average optical density of p‐ERK, ERK (p = 0.004, and p = 0.026, respectively) and level of mRNA concentration of ERK (p = 0.001) were significantly decreased. Conclusion: Our study demonstrated that irisin could not only improve circulating insulin resistance, but may also improve ovarian IR through an increase in the activity of PI3K/AKT signaling and a decrease of MAPK/ERK signaling. [ABSTRACT FROM AUTHOR]

With the rapid development of intelligent electronic devices, and the demand for the shape of the electronic devices with different patterns, people have put forward higher requirements for the design and preparation of the corresponding energy storage devices. Graphene quantum dots are widely used due to their good properties. In this paper, graphene quantum dots were used as electrode materials for patterned planar micro-supercapacitors, and electrode film was prepared by a modified liquid-air interface self-assembly method with an electrode width/interdigital gap of 300 µm/100 µm. Then pattern design is conducted on this basis, and the patterned planar micro-energy storage device was prepared. The electrochemical properties of the devices were investigated at scan rates of 0.01–10000 Vs−1. At a scan rate of 0.01 Vs−1, the area capacitance and energy density were 12.52 µFcm−2 and 1.74 nWhcm−2, density was 44.36 µWcm−2. [ABSTRACT FROM AUTHOR]

Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvβ3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE's influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvβ3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvβ3. Activation of the integrin αvβ3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions. [ABSTRACT FROM AUTHOR]

BACKGROUND Currently, the use of mushrooms as functional foods, nutraceuticals or phytopharmaceuticals source has risen. In contrast, the possible cellular cytotoxicity and immunostimulatory activity of Pleurotus eryngii ( DC. ex Fr.) Quel protein ( PEQP) is unknown. Here we report extraction, anti-tumorigenic and immunostimulatory activity of PEQP in vitro. RESULTS PEQP was extracted from the dried fruiting bodies of P. eryngii, purified and characterised. Its in vitro antiproliferative activity was then evaluated in human non-small cell lung cancer A549 ( NSCLC), stomach adenocarcinoma BGC-823, hepatocellular carcinoma HepG2 and gastric carcinoma HGC-27 cell lines using conventional cancer drugs (paclitaxel, doxorubicin and mitomycin C) as positive controls. The protein fractions ( PEQP 1, 2, 3 and 4) obtained inhibited tumour cell proliferation dose-dependently with fraction PEQP 2 having significant ( P < 0.05) toxicity in all tumour cells. PEQP had no significant toxicity on normal liver Chang cells but their proliferation was significantly inhibited by mitomycin C. Moreover, PEQP stimulated the proliferation, lysosomal enzyme activity, pinocytosis, nitric oxide and hydrogen peroxide production of RAW 264.7 cell lines dose-dependently. CONCLUSION Based on these results, P. eryngii protein has a potential application in functional foods as a natural anti-tumour agent with immunostimulatory activity. © 2014 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Hyperlipidemia poses a serious threat to human health, but its medication remains some issues including significant adverse reactions. Polyphenols exhibit great potential in lowering blood lipids and the lipid-lowering effects of quinoa polyphenols are still waiting to be explored. In this study, a deep eutectic solvent-based ultrasonic-assisted extraction method of quinoa polyphenols was developed. Then, the constituents of quinoa polyphenols after purification CQP were analyzed. Besides, their lipid-lowering activities and mechanism were explored. Results suggested that CQP comprised at least 12 kinds of polyphenols. CQP could inhibit lipase, adsorb cholesterol, inhibit oxidative stress and lipid peroxidation. Subsequent network pharmacology, cellular experiments and molecular docking revealed that CQP might influence the expression levels or bind to AKT1 and FOXO1, thereby affecting their content or activity, ultimately regulating their functions and leading to changes of the cellular lipid levels. This study lays foundation for developing novel lipid-lowering drugs and functional foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim: The present study is to investigate the association between T790M status and clinical characteristics of patients with EGFR-sensitive advanced non-small cell lung cancer (NSCLC) who progressed the initial epidermal growth factor receptor tyrosine kinase inhibitors (EGFRTKIs) administration., Methods: A total of 167 patients with EGFR-sensitive mutations advanced NSCLC who had successful genetic tests and progressed the initial EGFR-TKI treatment were included in this study retrospectively. The clinical and demographic characteristics of these patients were collected, which were manifested as pathological type, metastasis location, initial biopsy method, initial genetic test specimens, and baseline gene mutations status. Correlation analysis between T790M status and these characteristics was performed and prognostic analysis regarding the different subgroups was carried out accordingly., Results: The prevalence of secondary T790M after resistance to initial EGFR-TKIs among the 167 patients was 52.7%. Correlation analysis indicated that the median progression-free Survival (PFS) to initial EGFR-TKIs >12 months were more likely to develop secondary T790M in univariate analysis. However, the conclusion failed to show statistically significant in multivariate analysis. Additionally, patients with intracranial progression of initial EGFR-TKIs therapy were associated with secondary EGFR-T790M. However, it should be noted that those whose best overall response was partial response (PR) during the EGFR-TKI therapy were relevant to secondary T790M. Furthermore, The median PFS of the initial EGFR-TKIs administration was longer among patients with T790M positive mutation and patients with PR reaction than those without T790M mutation and patients with stable disease (SD), respectively (median PFS: 13.6 vs. 10.9 months, P=0.023) and (median PFS: 14.0 vs. 10.1 months, P=0.001)., Conclusion: This retrospective study highlighted the real-world evidence that the best efficacy and intracranial progression with initial EGFR-TKIs therapy among patients with advanced NSCLC might be the promising indicators to predict the occurrence of EGFR-T790M. Patients with PR reaction and T790M positive mutation conferred longer PFS of the initial EGFR-TKIs administration. Also, the conclusion should be confirmed in more patients with advanced NSCLC subsequently., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)