An endothelial cell monolayer separates interstitia from blood and lymph, and determines the bidirectional transfer of solutes and macromolecules across these biological spaces. We review advances in transport modalities across these endothelial barriers. Glucose is a major fuel for the brain and peripheral tissues, and insulin acts on both central and peripheral tissues to promote whole-body metabolic signalling and anabolic activity. Blood-brain barrier endothelial cells display stringent tight junctions and lack pinocytic activity. Delivery of blood glucose and insulin to the brain occurs through their respective carrier (Glucose transporter 1) and receptor (insulin receptor), enacting bona fide transcytosis. At supraphysiological concentrations, insulin is also likely transferred by fluid phase cellular uptake and paracellular transport, especially in peripheral microvascular endothelia. The lymphatic microvasculature also transports insulin but in this case from tissues to lymph and therefrom to blood. This serves to end the hormone's action and to absorb highly concentrated subcutaneously injected insulin in diabetic individuals. The former function may involve receptor-mediated transcytosis into lymphatic endothelial cells, the latter fluid phase uptake and paracellular transport. Lymphatic capillaries also mediate carrierdependent transport of other nutrients and macromolecules. These findings challenge the notion that lymphatic capillaries only transport macromolecules through intercellular flaps. K E Y W O R D S blood capillaries, blood-brain barrier, endothelial cells, glucose transporter, glucose uptake, insulin delivery, insulin receptor, lymphatic capillaries, paracellular transport, transcytosis 1 | INTRODUCTION Endothelial cell layers of blood and lymphatic capillaries define the separation between the blood or lymph fluids in our body and the parenchymal tissues they supply and void. As such, they constitute a phenomenal barrier to the free diffusion of fluids, and of small and large molecules, as well as of cells of the immune system. While considering general principles, we mainly focus this review on the exquisite filter function of blood vascular endothelia for glucose, a foremost important nutrient for all tissues, and for insulin, a key metabolic and growth regulator. These constitute examples of the endothelial selectivity filters for small and large molecules, respectively.The reader is also referred to an excellent analysis by Fung et al 1 on the molecular barrier function of epithelial and endothelial cells. We further discuss the opposite transport of diverse molecules across the comparatively lesser studied lymphatic vessels. Throughout, we Javier R. Jaldin-Fincati and Rafaela V. S. Pereira contributed equally to this study.

Nuclear factor-kappaB (NF-kappaB) is one of the most important transcription factors; it has a key role in inflammatory and immune responses, cell adhesion, developmental signals, and anti-apoptosis process. Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are major causes of morbidity and mortality worldwide. In this review, we highlight the role of NF-kappaB in inflammatory lung disease, the strategies which block the activation of NF-kappaB, and the therapeutic approaches to treating inflammatory lung disease.

Clinicopathological features and pathogenesis of esophageal small-cell carcinoma remain unclear. We hypothesized common cellular origin and pathogenesis in small-cell carcinoma of esophagus and lung associated with SOX2 overexpression and loss of Rb1. Expression of squamous-basal markers (CK5/6 and p40), glandular markers (CK18 and CEA), SOX2, and Rb1 were evaluated in 15 esophageal small-cell carcinomas, 46 poorly differentiated squamous cell carcinomas, and 88 small-cell lung carcinoma, as well as 16 embryonic esophagus. Esophageal small-cell carcinoma expressed higher levels of glandular markers and lower levels of squamous-basal markers than poorly differentiated squamous cell carcinoma. No significant differences were observed in immunohistochemistry profiles between small-cell carcinoma of the esophagus and the lung. SOX2 expression was high in esophageal small-cell carcinoma (70%±33% of nuclei), small-cell lung carcinoma (70%±26%), and the embryonic esophagus (75%±4%), and it was significantly lower in poorly differentiated squamous cell carcinoma (29%±28%). Rb1 expression was significantly lower in esophageal small-cell carcinoma (0.3%±1%), small-cell lung carcinoma (2%±6%), and the embryonic esophagus (7%±5%), and it was significantly higher in poorly differentiated squamous cell carcinoma (51%±24%). The immunohistochemistry profiles of small-cell carcinoma of the esophagus and the lung are highly similar. The loss of Rb1 function is a key contributor to the pathogenesis of both neoplasms. In addition, SOX2 overexpression observed in esophageal and lung small-cell carcinoma as well as in the embryonic esophagus indicated that esophageal small-cell carcinoma may arise from embryonic-like stem cells in the esophageal epithelium. The two distinct differentiation patterns (neuroendocrine and glandular) of esophageal small-cell carcinoma further support the fact that SOX2 has a pivotal role in the differentiation of pluripotent stem cells into esophageal small-cell carcinoma cells.

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