In adults, the ovary is characterized with extensive angiogenesis and regular intervals of rapid growth. Ovarian function is dependent on the network of angiogenic vessels which enable the follicle and/or corpus luteum to receive oxygen, nutrients and hormonal support. Abnormal angiogenesis is involved in the induction and development of pathological ovary, such as polycystic ovary syndrome and ovarian cancer. Notch signalling pathway is one of the primary regulators of angiogenesis and a therapeutic target for ovarian diseases. Here, we will review literatures on the expression pattern of Notch pathway components in the ovary and on the role of Notch signalling pathway on ovarian angiogenesis.

Manganese (Mn) is an essential micronutrient. However, it is well established that Mn overexposure causes nervous system diseases. In contrast, there are few reports on the effects of Mn exposure on glomerular endothelium. In the present study, the potential effects of Mn exposure on glomerular endothelium were evaluated. Sprague Dawley rats were used as a model of Mn overexposure by intraperitoneal injection of MnCl₂·H₂O at 25 mg/kg body weight. Mn exposure decreased expression of vascular endothelial-cadherin, a key component of adherens junctions, and increased exudate from glomeruli in Sprague Dawley rats. Human renal glomerular endothelial cells were cultured with different concentration of Mn. Exposure to 0.2 mM Mn increased permeability of human renal glomerular endothelial cell monolayers and decreased vascular endothelial-cadherin expression without inducing cytotoxicity. In addition, Mn exposure increased phosphorylation of mothers against decapentaplegic homolog 2/3 and upregulated expression of zinc finger protein SNAI1, a negative transcriptional regulator of vascular endothelial-cadherin. Our data suggest Mn exposure may contribute to development of glomerular diseases by inducing permeability of glomerular endothelium.

Angiogenesis is required for the growth and metastasis of solid tumors. The anti-malarial agent dihydroartemisinin (DHA) demonstrates potent anti-angiogenic activity, but the underlying molecular mechanisms are not yet fully understood. During the process of angiogenesis, endothelial cells migrating from existing capillaries may undergo programmed cell death after detaching from the extracellular matrix, a process that is defined as anchorage‑dependent apoptosis or anoikis. In the present study, DHA‑induced cell death was compared in human umbilical vein endothelial cells (HUVECs) cultured in suspension and attached to culture plates. In suspended HUVECs, the cell viability was decreased and apoptosis was increased with the treatment of 50 µM DHA for 5 h, while the same treatment did not affect the attached HUVECs. In addition, 50 µM DHA increased the phosphorylation of c‑Jun N‑terminal kinase (JNK) in suspended HUVECs, but not in attached HUVECs, for up to 5 h of treatment. The JNK inhibitor, SP600125, reversed DHA‑induced cell death in suspended HUVECs, suggesting that the JNK pathway may mediate DHA‑induced endothelial cell anoikis. The data from the present study indicates a novel mechanism for understanding the anti-angiogenic effects of DHA, which may be used as a component for chemotherapy.

Background: Cadmium (Cd) is an environmental pollutant that leads to nephrotoxicity. However, the mechanisms of Cd-induced glomerular injury have not been fully clarified. Von Willebrand factor (vWF) and occludin are important endothelial cell markers in renal vasculature. In this study, the effects of Cd on the vWF and occludin expression in mouse glomeruli was investigated. Objectives: The goal of this study was to analyze the expression of von Willebrand factor and occludin in glomerular endothelial cells of tumor necrosis factor-α^−/− (TNF-α^−/−) mice after treatment with Cd. Material and methods: C57BL6/J wild-type (WT) mice and TNF-α^−/− mice (n = 6) were treated with Cd, and the kidney tissues were collected. The expression of von Willebrand factor and occludin was detected by using quantitative real-time PCR, immunofluorescence, and immunohistochemistry. In vitro, Human umbilical vascular endothelial cells (HUVECs) were used to examine the regulatory role of TNF-α on expression of von Willebrand factor and occludin. Results: We found that Cd significantly increases mRNA and protein expressions of von Willebrand factor and occludin in TNF-α^−/− mice, but not in WT mice. In vitro, Cd significantly increased mRNA and protein expression of von Willebrand factor and occludin in HUVECs with TNF-α small interfering RNA (siRNA) transfection. Conclusions: These results suggest that TNF-α acts to balance homeostasis of glomerular endothelium after Cd treatments.

Background: Inflammatory bowel disease (IBD) is the most common precancerous lesion of colitis-associated colon cancer (CAC). Studies have confirmed that pathological changes in intestinal lymphatic vessels (LVs) significantly promoted the development of IBD-associated carcinogenesis. An imbalance in the microecology of the intestinal flora is a key factor in the progression of IBD. As a result, therapeutic techniques that focus on the relationship between LV regeneration and flora management might be a potential treatment strategy. Methods: We investigated the role of Clostridium butyricum (C butyricum) in a dextran sulfate sodium (DSS)-induced IBD mouse model. Balb/c mice were given 3% DSS in their drinking water for 8 days to produce acute colitis and simultaneously administrated with C butyricum for 12 days. Hematoxylin and eosin (H&E) staining was used to evaluate the degree of colitis tissue damage. Levels of the lymphatic endothelial cell (LEC)-specific marker LYVE-1 and intestinal expressions of pro-lymphatic vascular endothelial growth factor (VEGF)-C and VEGF-D were determined using immunohistochemical assays. Results: In a DSS-induced IBD mouse model, we found that butyric acid-producing C butyricum significantly reduced disease activity index (DAI) scores in mice, reversed the shortening of the colon, weakened the degree of damage to colonic epithelial tissues, inhibited lymphocyte infiltration, and reduced pathological damage to the colon. To our knowledge, this is the first time that tissue expressions of LYVE-1, VEGF-C, and VEGF-D have been seen to increase in IBD-model mice after treatment with C butyricum. Conclusions: Our findings suggest that C butyricum might alleviate IBD in DSS-induced IBD-model mice by promoting intestinal LV regeneration.