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Pluripotent stem cell-derived organoids have transformed our ability to recreate complex three-dimensional models of human tissue. However, the directed differentiation methods used to create them do not afford the ability to introduce cross-germ-layer cell types. Here, we present a bottom-up engineering approach to building vascularized human tissue by combining genetic reprogramming with chemically directed organoid differentiation. As a proof of concept, we created neuro-vascular and myo-vascular organoids via transcription factor overexpression in vascular organoids. We comprehensively characterized neuro-vascular organoids in terms of marker gene expression and composition, and demonstrated that the organoids maintain neural and vascular function for at least 45 days in culture. Finally, we demonstrated chronic electrical stimulation of myo-vascular organoid aggregates as a potential path toward engineering mature and large-scale vascularized skeletal muscle tissue from organoids. Our approach offers a roadmap to build diverse vascularized tissues of any type derived entirely from pluripotent stem cells., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Diazinon (DZN) is an organophosphate pesticide that is commonly used in agriculture worldwide, including in Iran, and unfortunately, it leads to a variety of negative effects on the environment, animals, and humans. Alpha-lipoic acid (ALA) is an antioxidant agent that acts via scavenging of oxygen-free radicals. Collagen IV is a component of the main base membrane structure and DZN may also affect the expression of this key protein. The aim of this study was to evaluate antioxidant properties of ALA on the expression of collagen IV, renal function, and oxidative stress induced by DZN in renal tissue. In this experimental study, 30 adult male Wistar rats were randomly divided into five groups (n = 6) including: the control group, DZN (40 mg/kg) group, ALA (100 mg/kg) group, ALA (100 mg/kg) + DZN (40 mg/kg) group, and sham group. On day 0 and after 6 weeks, the urine and blood samples were collected to measure glomerular filtration rate (GFR). After 6 weeks, the rats were anesthetized and the left kidney was used for immunohistochemistry study and the right kidney was used to evaluate the oxidative stress parameters. The results have shown that ALA significantly improved the biochemical parameters including superoxide dismutase, glutathione peroxidase, glutathione S-transferase, glutathione reductase, and GFR. In addition, ALA significantly prevented the expression of collagen IV that was changed by DZN administration in rats. We concluded that when exposed to DZN, depletion of antioxidant enzymes is accompanied by the induction of oxidative stress that might be beneficial in monitoring DZN toxicity and alpha-lipoic acid, as an antioxidant can overcome the toxicity induced by DZN in the kidney.

Aim: To determine the relationship between breast stiffness assessed with sonoelastography (elasticity) and breast tissue density assessed with mammography (MG) and ultrasound (US)., Methods: This cross-sectional study involved 100 women who underwent MG, gray-scale US, and shear-wave sonoelastography during 2013. Mammographic density was categorized into four groups and sonographic density into three groups according to Breast Imaging-Reporting and Data System criteria. The stiffness of breast parenchymal and adipose tissue in all breast quadrants was quantified by shear-wave sonoelastography. Mean elastographic estimates were compared with MG- and US-derived density estimates., Results: Parenchymal and adipose tissue elasticity positively correlated with MG- and US-derived breast density (for parenchyma: for MG Kendall's tau b 0.522; Jonckheere-Terpstra test P<0.001 and for US Kendall's tau b 0.533; Jonckheere-Terpstra test P<0.001); the higher was the breast density on MG and US, the higher was the elastographic stiffness., Conclusion: Sonoelastographic breast stiffness strongly positively correlated with breast density. Thus, sonoelastography may have a potential for estimating the breast cancer risk, which allows a novel application of this technique in routine clinical practice.

Liver regeneration is crucial for the maintenance of liver functional mass during homeostasis and diseases. In a disease context-dependent manner, liver regeneration is contributed to by hepatocytes or progenitor cells. As long as they are replicatively competent, hepatocytes are the main cell type responsible for supporting liver size homeostasisand regeneration. The concept that all hepatocytes within the lobule have the same proliferative capacity but are differentially recruited according to the localization of the wound, or whether a yet to be defined sub-population of hepatocytes supports regeneration is still debated. In a chronically or severely injured liver, hepatocytes may enter a state of replicative senescence. In such conditions, small biliary cells activate and expand, a process called ductular reaction (DR). Work in the last few decades has demonstrated that DR cells can differentiate into hepatocytes and thereby contribute to parenchymal reconstitution. In this study we will review the molecular mechanisms supporting these two processes to determine potential targets that would be amenable for therapeutic manipulation to enhance liver regeneration., Competing Interests: The authors declare no conflict of interest.

Objectives: Accumulation of intrapancreatic fat may be important in type 2 diabetes, but widely varying data have been reported. The standard quantification by MRI in vivo is time consuming and dependent upon a high level of experience. We aimed to develop a new method which would minimise inter-observer variation and to compare this against previously published datasets., Methods: A technique of 'biopsying' the image to minimise inclusion of non-parenchymal tissues was developed. Additionally, thresholding was applied to exclude both pancreatic ducts and intrusions of visceral fat, with pixels of fat values of <1% or >20% being excluded. The new MR image 'biopsy' (MR-opsy) was compared to the standard method by 6 independent observers with wide experience of image analysis but no experience of pancreas imaging. The effect of the new method was examined on datasets from two studies of weight loss in type 2 diabetes., Results: At low levels of intrapancreatic fat neither the result nor the inter-observer CV was changed by MR-opsy, thresholding or a combination of the methods. However, at higher levels the conventional method exhibited poor inter-observer agreement (coefficient of variation 26.9%) and the new combined method improved the CV to 4.3% (p<0.03). Using either MR-opsy alone or with thresholding, the new methods indicated a closer relationship between decrease in intrapancreatic fat and fall in blood glucose., Conclusion: The inter-observer variation for quantifying intrapancreatic fat was substantially improved by the new method when pancreas fat levels were moderately high. The method will improve comparability of pancreas fat measurement between research groups.

Background: Although occupational exposures contribute to a significant proportion of obstructive lung disease, the phenotype of obstructive lung disease associated with work-related organic dust exposure independent of smoking remains poorly defined., Objective: We identified the relative contributions of smoking and occupational endotoxin exposure to parenchymal and airway remodeling as defined by quantitative computed tomography (CT)., Methods: The Shanghai Textile Worker Study is a longitudinal study of endotoxin-exposed cotton workers and endotoxin-unexposed silk workers that was initiated in 1981. Spirometry, occupational endotoxin exposure, and smoking habits were assessed at 5-year intervals. High-resolution computed tomography (CT) was performed in 464 retired workers in 2011, along with quantitative lung densitometric and airway analysis., Results: Significant differences in all CT measures were noted across exposure groups. Occupational endotoxin exposure was associated with a decrease (-1.3%) in percent emphysema (LAAI-950), a 3.3-Hounsfield unit increase in 15th percentile density, an 18.1-g increase in lung mass, and a 2.3% increase in wall area percent. Current but not former smoking was associated with a similar CT phenotype. Changes in LAAI-950 were highly correlated with 15th percentile density (correlation -1.0). Lung mass was the only measure associated with forced expiratory volume in 1 sec (FEV1) decline, with each 10-g increase in lung mass associated with an additional loss (-6.1 mL) of FEV1 (p = 0.001) between 1981 and 2011., Conclusions: There are many similarities between the effects of occupational endotoxin exposure and those of tobacco smoke exposure on lung parenchyma and airway remodeling. The effects of occupational endotoxin exposure appear to persist even after the cessation of exposure. LAAI-950 may not be a reliable indicator of emphysema in subjects without spirometric impairment. Lung mass is a CT-based biomarker of accelerated lung function decline., Citation: Lai PS, Hang J, Zhang F, Sun J, Zheng BY, Su L, Washko GR, Christiani DC. 2016. Imaging phenotype of occupational endotoxin-related lung function decline. Environ Health Perspect 124:1436-1442; http://dx.doi.org/10.1289/EHP195., Competing Interests: The authors declare they have no actual or potential competing financial interests.