(-)-Epigallocatechin-3-gallate,reduces corneal damage secondary from experimental grade II alkali burns in mice

Background

Since recent reports have shown that (-)-Epigallocatechin-3-gallate (EGCG) could be used for treating proliferative and inflammatory disorders, we explored its use for the management of corneal chemical burns.

低密度脂蛋白在2型糖尿病骨质疏松中的作用研究进展

2型糖尿病及骨质疏松已成为我国最主要的慢性代谢性疾病。2型糖尿病常伴有血脂紊乱，常表现为低密度脂蛋白升高，而越来越多的研究表明血脂通过不同的方式影响骨代谢，其机制可能是通过抑制骨髓间充质干细胞成骨分化，通过RANK/RNAKL/OPG信号通路及炎症反应调节破骨细胞等方式调节骨代谢。     

Immune Checkpoint Inhibitor Toxicities

Immune checkpoint inhibitors are molecules that increase the endogenous immune response against tumors. They have revolutionized the field of oncology. Since their initial approval for the treatment of advanced melanoma, their use has expanded to the treatment of several other advanced cancers. Unfortunately, immune checkpoint inhibitors have also been associated with the emergence of a new subset of autoimmune-like toxicities, known as immune-related adverse events. These toxicities differ depending on the agent, malignancy, and individual susceptibilities. Although the skin and colon are most commonly involved, any organ may be affected, including the liver, lungs, kidneys, and heart. Most of these toxicities are diagnosed by excluding other secondary infectious or inflammatory causes. Corticosteroids are commonly used for treatment of moderate and severe immune-related adverse events, although additional immunosuppressive therapy may occasionally be required. The occurrence of immune-related toxicities may require discontinuation of immunotherapy, depending on the specific toxicity and its severity. In this article, we provide a focused review to familiarize practicing clinicians with this important topic given that the use of immune checkpoint inhibitors continues to increase.     

“Real life” polycyclic aromatic hydrocarbon (PAH) mixtures modulate hCG,hPL and hPLGF levels and disrupt the physiological ratio of MMP-2 to MMP-9 and VEGF expression in human placenta cell lines

Using JEG-3 and BeWo cells, we examined the effect of “real life” mixtures of polycyclic aromatic hydrocarbons (PAHs), at doses reported in maternal blood (Mix I) and in placental tissue (Mix II), on human chorionic gonadotropin (hCG), placental lactogen (hPL) and placental growth factor (hPLGF) secretion, protein expression and immunolocalization. Additionally, the action of PAH mixtures on basal and hormone-stimulated matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) protein expression was evaluated. Under basal conditions, the PAH mixtures increased hCG and decreased hPLGF levels in both cell lines, while hPL expression was stimulated in JEG-3 and inhibited in BeWo. There was no effect on the MMP-2/MMP-9 ratio or VEGF expression. In hormone-stimulated cells, PAH mixtures changed the MMP-2/MMP-9 ratio in JEG-3 cells in favor of MMP-9, while in BeWo MMP-2 was favored. The effect on VEGF expression was cell specific and dependent on the mixture. In hCG-treated cells, only Mix II inhibited VEGF expression in JEG-3 cells. Neither PAH mixtures affected this protein in BeWo cells. In hPL-treated cells, Mix I had a stimulatory effect in JEG-3 cells, while Mix II exerted an inhibitory effect in BeWo cells. In hPLGF-treated cells, Mix II decreased in JEG-3 cells, but in BeWo cells, both mixtures increased VEGF expression. Considering that the evaluated protein hormones play crucial roles in angiogenesis and neovascularization in the placenta, “real life” PAH mixtures by disrupting protein hormones levels, the MMP-2/MMP-9 ratio and VEGF expression can lead to insufficiency and many pregnancy-related disorders.     

Engraftable neural crest stem cells derived from cynomolgus monkey embryonic stem cells

Neural crest stem cells (NCSCs), a population of multipotent cells that migrate extensively and give rise to diverse derivatives, including peripheral and enteric neurons and glia, craniofacial cartilage and bone, melanocytes and smooth muscle, have great potential for regenerative medicine. Non-human primates provide optimal models for the development of stem cell therapies. Here, we describe the first derivation of NCSCs from cynomolgus monkey embryonic stem cells (CmESCs) at the neural rosette stage. CmESC-derived neurospheres replated on polyornithine/laminin-coated dishes migrated onto the substrate and showed characteristic expression of NCSC markers, including Sox10, AP2α, Slug, Nestin, p75, and HNK1. CmNCSCs were capable of propagating in an undifferentiated state in vitro as adherent or suspension cultures, and could be subsequently induced to differentiate towards peripheral nervous system lineages (peripheral sympathetic neurons, sensory neurons, and Schwann cells) and mesenchymal lineages (osteoblasts, adipocytes, chondrocytes, and smooth muscle cells). CmNCSCs transplanted into developing chick embryos or fetal brains of cynomolgus macaques survived, migrated, and differentiated into progeny consistent with a neural crest identity. Our studies demonstrate that CmNCSCs offer a new tool for investigating neural crest development and neural crest-associated human disease and suggest that this non-human primate model may facilitate tissue engineering and regenerative medicine efforts.     

Macroporous thin membranes for cell transplant in regenerative medicine

The aim of this paper is to present a method to produce macroporous thin membranes made of poly (ethyl acrylate-co-hydroxyethyl acrylate) copolymer network with varying cross-linking density for cell transplantation and prosthesis fabrication. The manufacture process is based on template techniques and anisotropic pore collapse. Pore collapse was produced by swelling the membrane in acetone and subsequently drying and changing the solvent by water to produce 100 microns thick porous membranes. These very thin membranes are porous enough to hold cells to be transplanted to the organism or to be colonized by ingrowth from neighboring tissues in the organism, and they present sufficient tearing stress to be sutured with surgical thread. The obtained pore morphology was observed by Scanning Electron Microscope, and confocal laser microscopy. Mechanical properties were characterized by stress–strain experiments in tension and tearing strength measurements. Morphology and mechanical properties were related to the different initial thickness of the scaffold and the cross-linking density of the polymer network. Seeding efficiency and proliferation of mesenchymal stem cells inside the pore structure were determined at 2 h, 1, 7, 14 and 21 days from seeding.     

Impact of overweight and obesity on US renal cell carcinoma incidence trends (1995-2018)

In the United States, renal cell carcinoma (RCC) incidence and the prevalence of obesity, an established risk factor for RCC, have been increasing for several decades. RCC is more common among older individuals. We sought to quantify the contribution of excess adiposity to the rising incidence of RCC among individuals 60 years or older. National Institutes of Health-American Association of Retired Persons Diet and Health Study data (n = 453 859 participants, enrolled in 1995-1996, age at enrollment 50-71 years) were used to estimate multivariable-adjusted hazard ratios (HRs) for RCC across body mass index categories and HRs associated with smoking. Population attributable fractions (PAFs) were calculated using estimated HRs and annual overweight/obesity prevalence from the National Health Interview Survey (1985-2008). PAF estimates were combined with RCC incidence from Surveillance, Epidemiology and End Results-13 to calculate annual percent changes in RCC incidence attributable (and unrelated) to overweight/obesity. We found that between 1995 and 2018, among individuals aged 60 years and older, PAF for overweight/obesity increased from 18% to 29% for all RCCs. In comparison, the PAF for smoking declined from 12% to 9%. RCC incidence increased 1.8% per year (95% confidence interval [CI] 1.5%-2.1%) overall, while RCC incidence attributable to overweight/obesity increased 3.8% per year (95%CI 3.5%-4.2%) and RCC incidence unrelated to overweight/obesity increased 1.2% per year (95% CI 0.9%-1.4%). In conclusion, overweight/obesity appears to have contributed importantly to the rising incidence of RCC in the United States since the mid-1990s. Public health interventions focused on reducing overweight and obesity could help substantially in curbing this trend.