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Phosphoinositide 3-kinase δ inactivation prevents vitreous-induced activation of AKT/MDM2/p53 and migration of retinal pigment epithelial cells

Han H, Chen N, Huang X, Liu B, Tian J, Lei H

J Biol Chem, 2019 10 18;294(42):15408-15417.
PMID: 31467081 DOI: 10.1074/jbc.RA119.010130

Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that play a critical role in transmitting signals from cell-surface molecules to intracellular protein effectors. Key PI3Ks include PI3Kα, PI3Kβ, and PI3Kδ, which are regulated by receptors. The signaling pathway comprising the PI3Ks, along with a Ser/Thr kinase (AKT), a proto-oncogene product (mouse double minute (MDM)2), and a tumor suppressor protein (p53), plays an essential role in experimental proliferative vitreoretinopathy (PVR), which is a fibrotic blinding eye disorder. However, which PI3K isoforms are involved in PVR is unknown. A major characteristic of PVR is the formation of epi (or sub)-retinal membranes that consist of extracellular matrix and cells, including retinal pigment epithelium (RPE) cells, glial cells, and macrophages. RPE cells are considered key players in PVR pathogenesis. Using immunoblotting and immunofluorescence analyses, we herein provide the evidence that PI3Kδ is highly expressed in human RPEs when it is primarily expressed in leukocytes. We also found that PI3Kδ inactivation through two approaches, CRISPR/Cas9-mediated depletion and a PI3Kδ-specific inhibitor (idelalisib), not only blocks vitreous-induced activation of AKT and MDM2 but also abrogates a vitreous-stimulated decrease in p53. Furthermore, we demonstrate that PI3Kδ inactivation prevents vitreous-induced proliferation, migration, and contraction of human RPEs. These results suggest that PI3Kδ may represent a potential therapeutic target for RPE-related eye diseases, including PVR.
Fulltext Capilliposide B blocks VEGF-induced angiogenesis in vitro in primary human retinal microvascular endothelial cells

Han H, Yang Y, Wu Z, Liu B, Dong L, Deng H, et al.

Biomed Pharmacother, 2021 Jan;133:110999.
PMID: 33227710 DOI: 10.1016/j.biopha.2020.110999

Abnormal angiogenesis is associated with intraocular diseases such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, and current therapies for these eye diseases are not satisfactory. The purpose of this study was to determine whether capilliposide B (CPS-B), a novel oleanane triterpenoid saponin derived from Lysimachia capillipes Hemsl, can inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis signaling events and cellular responses in primary human retinal microvascular endothelial cells (HRECs). Our study revealed that the capilliposide B IC50 for HRECs was 8.5 μM at 72 h and that 1 μM capilliposide B specifically inhibited VEGF-induced activation of VEGFR2 and its downstream signaling enzymes Akt and Erk. In addition, we discovered that this chemical effectively blocked VEGF-stimulated proliferation, migration and tube formation of the HRECs, suggesting that capilliposide B is a promising prophylactic for angiogenesis-associated diseases such as proliferative diabetic retinopathy.
Fulltext The prevalence and its associated factors of psychological stress among middle school students in China: pooled evidence from a systematic scoping review

Hao L, Mat Ludin AF, Ahmad M, Meng X, Zhong Lei H

Front Public Health, 2024;12:1358210.
PMID: 38694991 DOI: 10.3389/fpubh.2024.1358210

Psychological issues are of significant concern in present-day society, as poor mental well-being results in depression and suicidal behavior. Understanding the current situation of psychological stress among secondary school students will help policy makers to formulate targeted measures to help them cope with stress, and at the same time evaluate the effectiveness of the existing policies to address the shortcomings and enhance the diversification of interventions. The main purpose of this review was to map the existing evidence on the prevalence and levels of psychological stress among adolescents in China, and to identify the associated risk factors. This review strictly adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A comprehensive search was performed spanning Web of Science, PubMed, and Scopus databases. Studies involving only humans and full text in English were selected. Selection was limited to samples from mainland China, Hong Kong, Macau, and Taiwan. Variables were extracted, exploring the factors that affected the mental wellness of Chinese middle school students. A final 15 articles and 1 report were included. The findings revealed psychological stress is prevalent among Chinese middle school population, with the degree of prevalence from low to severe stress levels. Three dimensions of psychological stress affecting Chinese secondary school students: school, family and lifestyle. Within the school, the factors included academic stress, peer relationships etc. Family-related factors were comprised of parent-child relationship, parents' mental health status etc. Lastly, lifestyle-related factors included poor diet, sedentary and inactivity etc. Our findings suggest that policy makers should reduce the excessive emphasis on examination results and focus on the all-round development of students, and that schools should organize a variety of extra-curricular activities to reduce students' stress. Parents should create a harmonious family atmosphere to minimize conflicts and maintain close communication with teachers.
SYSTEMATIC REVIEW REGISTRATION: OSF; https://doi.org/10.17605/OSF.IO/HEFCP.
Pectin-interactions and the digestive stability of anthocyanins in thermal and non-thermal processed strawberry pulp

Xing Y, Wang K, Zhang M, Law CL, Lei H, Wang J, et al.

Food Chem, 2023 Oct 30;424:136456.
PMID: 37267648 DOI: 10.1016/j.foodchem.2023.136456

This study investigated the digestive stability of anthocyanins (ACNs) and their interaction with three pectin fractions-water-soluble pectin (WSP), cyclohexanetrans-1,2-diamine tetra-acetic acid-soluble pectin (CSP), and sodium carbonate-soluble pectin (NSP)-in strawberry pulp processed by pasteurization (PS), ultrasound (US), electron beam (EB) irradiation, and high pressure (HP). Compared with the control group, the ACNs content increased to the highest level (312.89 mg/mL), but the retention rate of ACNs in the simulated intestine decreased significantly after US treatment. The monosaccharide compositions indicated that the WSP and CSP possessed more homogalacturonan (HG) domains than the NSP, which contains more rhamngalacturonan-I (RG-I) domains. The microstructure of US-treated pectin was damaged and fragmented. Comprehensive analysis showed that the retention rate of ACNs was closely related to the pectin structure, primarily reflected by the degree of linearity and the integrity of structure. These results revealed the structure-activity relationship between ACNs and pectin during pulp processing.