Involvement of apoptosis in ovarian follicular atresia and postovulatory regression.

In the ovary, greater than 99% of the follicles present at birth are destined to degenerate during life. In humans, less than 400 of the more than 400,000 follicles found at puberty will eventually ovulate whereas the overwhelming majority of follicles undergo atresia. Although follicular atresia plays a critical role during the recruitment of follicles for ovulation, the exact mechanism of this process is unknown. In chicken and porcine ovaries, atretic follicles can be morphologically distinguished from their healthy counterparts of the same size. Adapting a sensitive 3'-end labeling method for DNA analysis, we identified internucleosomal cleavage of cellular DNA in atretic (but not normal) follicles of both animal species, resembling that found during programmed cell death in embryogenesis, autoimmune T-cell removal and prostate regression. The present findings provide a basis for elucidating the hormonal signals involved in the initiation of follicular atresia during follicle recruitment, reproductive aging and premature ovarian failure.     

Gonadotroph adenomas in men produce biologically active follicle-stimulating hormone

Gonadotroph adenomas may exhibit qualitative and quantitative defects in gonadotropin biosynthesis and secretion. Hypersecretion of immunoreactive FSH dimers by these adenomas occurs frequently; however, it has not been known whether this FSH is biologically active. Using the granulosa cell aromatase bioassay and a highly specific immunoradiometric assay for FSH, we studied the serum bioactivity and bio- to immunoactivity (B/I) ratios of 14 men with FSH-secreting adenomas and compared these values to those of 11 age-matched normal men. In addition, three adenoma patients received TRH (400 micrograms, iv). The mean basal serum FSH level (international units per L), as measured by both bio- and immunoassays, and the FSH B/I ratios were significantly higher (P less than 0.02, by Kolmogorov-Smirnov test) in the adenoma patients than in normal men (mean +/- SEM; adenoma patients: bioactivity, 68.8 +/- 10.4; immunoreactivity, 34.8 +/- 13.7; B/I ratio, 3.4 +/- 0.6; normal men: bioactivity, 5.8 +/- 1.2; immunoreactivity, 6.4 +/- 0.8; B/I ratio, 0.90 +/- 0.1). Both bio- and immunoactive FSH rose after TRH injection, resulting in maintenance of the B/I (mean +/- SEM; pre-TRH: bio-FSH, 63.7 +/- 22.4; immuno-FSH, 28.0 +/- 14.1; B/I ratio, 2.8 +/- 1.2; post-TRH: bio-FSH, 125.6 +/- 42.7; immuno-FSH, 45.8 +/- 21.8; B/I ratio, 3.5 +/- 1.6). When gonadotroph adenoma cells from three separate patients were cultured and their conditioned media (n = 3) studied, relatively large amounts of both bio- and immuno-FSH were detected. Furthermore, the major isoelectric profile of bio-FSH (pH 4.9-3.0) in the conditioned medium from two such adenomas was shown by chromatofocusing to be comparable to that of purified human pituitary FSH (pH 5.2-3.6). We conclude that gonadotroph adenomas in men secrete FSH that is biologically active, both basally and in response to TRH.     

Troglitazone inhibits formation of early atherosclerotic lesions in diabetic and nondiabetic low density lipoprotein receptor-deficient mice

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a ligand-activated nuclear receptor expressed in all of the major cell types found in atherosclerotic lesions: monocytes/macrophages, endothelial cells, and smooth muscle cells. In vitro, PPARgamma ligands inhibit cell proliferation and migration, 2 processes critical for vascular lesion formation. In contrast to these putative antiatherogenic activities, PPARgamma has been shown in vitro to upregulate the CD36 scavenger receptor, which could promote foam cell formation. Thus, it is unclear what impact PPARgamma activation will have on the development and progression of atherosclerosis. This issue is important because thiazolidinediones, which are ligands for PPARgamma, have recently been approved for the treatment of type 2 diabetes, a state of accelerated atherosclerosis. We report herein that the PPARgamma ligand, troglitazone, inhibited lesion formation in male low density lipoprotein receptor-deficient mice fed either a high-fat diet, which also induces type 2 diabetes, or a high-fructose diet. Troglitazone decreased the accumulation of macrophages in intimal xanthomas, consistent with our in vitro observation that troglitazone and another thiazolidinedione, rosiglitazone, inhibited monocyte chemoattractant protein-1-directed transendothelial migration of monocytes. Although troglitazone had some beneficial effects on metabolic risk factors (in particular, a reduction of insulin levels in the diabetic model), none of the systemic cardiovascular risk factors was consistently improved in either model. These observations suggest that the inhibition of early atherosclerotic lesion formation by troglitazone may result, at least in part, from direct effects of PPARgamma activation in the artery wall.     

Clinical Outcomes Following Covered Stent for the Treatment of Coronary Artery Perforation

Background

This study aimed to evaluate short‐ and long‐term outcomes of polytetrafluoroethylene covered stent for patients with coronary artery perforation.

Methods

During April 2004 and February 2016, a total 48 patients underwent implantation using polytetrafluoroethylene‐covered JOSTENT GraftMaster stents (Abbott Vascular, Santa Clara, CA) in the native coronary arteries implantation for coronary artery perforation. Clinical outcomes such as target lesion revascularization (TLR), myocardial infarction (MI), definite or possible stent thrombosis, cardiovascular mortality, and all‐cause mortality were analyzed.

Results

The average age of study patients was 68.02 ± 13.49 years, and the majorities were men (76.6%). The most frequent devices cause of perforation were stents (37.5%). Eighteen patients (37.5%) experienced cardiac tamponade and 20 patients (41.7%) underwent emergent pericardiocentesis. Only 1 patient (2.1%) experienced emergent surgical repair after covered stent. At the 30‐day follow‐up, the rate of all‐cause mortality was 16.7% and cardiovascular mortality was 13.0%. At the 1‐year follow‐up, the rate of MI was 6.1%, the rate of TLR was 21.9%, the rate of definite or possible stent thrombosis was 15.6%, the rate of cardiovascular mortality was 22.0%, and the rate of all‐cause mortality was 26.2%. Between the patients with and without cardiac tamponade, patients with cardiac tamponade had higher cardiovascular mortality in 30‐day and also higher all‐cause mortality in 30‐day and 1‐year follow‐up.

Conclusion

The covered stent could solve emergent condition for patients with coronary artery perforation with high TLR and stent thrombosis rate at long‐term follow‐up. The patients with cardiac tamponade had worse clinical outcomes in 30‐day and 1‐year follow‐up.

     

Ouabain promotes immune responses in WEHI‐3 cells to generate leukemia mice through enhancing phagocytosis and natural killer cell activities in vivo

Ouabain, a cardiotonic steroid, was used for the treatment of heart failure and atrial fibrillation and induces cancer cell apoptosis in many human cancer cells including human leukemia cells. However, there are no reports to show the effects on immune responses in a leukemia mouse model. In this study, WEHI‐3 cell generated leukemia mice were developed and treated by oral ouabain at 0, 0.75, 1.5, and 3 mg/kg for 15 days. Results indicated that ouabain did not affect body appearance, but decreased liver and spleen weights, B‐ and T‐cell proliferation at all three doses treatment and increased CD19 cells at 3.0 mg/kg treatment, decreased CD3, CD11b, and Mac‐3 cells levels compared with positive control. Furthermore, ouabain increased the macrophage phagocytosis from peripheral blood mononuclear cell and peritoneal cavity at all three doses treatment and increased NK cell activities. Ouabain restored GOT, GPT and LDH levels in WEHI‐3 leukemia mice in vivo.     

Associations between Plasma Folate and Vitamin B12, Blood Lead,and Bone Mineral Density among Adults and Elderly Who Received a Health Examination

This study hypothesized that plasma folate and vitamin B₁₂ levels modified the association between blood lead and cadmium and total urinary arsenic levels and bone loss. A total of 447 study subjects who received a physical examination at the Wanfang Hospital Medical Center were recruited. Bone loss was defined as a calcaneus bone mineral density T-score less than −1. Blood cadmium and lead concentrations were measured by ICP-MS. Urinary arsenic species were determined using HPLC-HG-AAS. A SimulTRAC-SNB radioassay was used to measure plasma folate, vitamin B₁₂, and homocysteine levels. Total urinary arsenic and blood lead concentration were positively correlated with the odds ratio (OR) for bone loss in a dose–response manner. The OR and 95% confidence interval (CI) for bone loss in participants with blood lead concentrations > 56.14 versus ≤33.82 μg/dL were 1.82 and 1.10–3.01. No correlation between plasma folate and vitamin B₁₂ levels alone and bone loss was observed. However, this study is the first observational study to find that blood lead concentrations tend to increase the OR of bone loss in a low plasma folate and plasma vitamin B₁₂ group with multivariate ORs (95% CI) of 2.44 (0.85–6.96).     

环状RNA在卵巢癌中的研究新进展

环状RNA(circular RNAs,circRNA)是具有多种特性和病理生理功能的非编码RNA网络热点成员.circRNA在表观遗传、转录和转录后调控水平上发挥作用.目前经过验证的涉及卵巢癌的内源性circRNA数量持续增加,且多种circRNA表达与卵巢癌的发生、侵袭和转移有关.此外,circRNA的异常表达也与...