Connexin-45 is expressed in mouse lymphatic endothelium and required for lymphatic valve function.

The expression and functional relevance of the gap junction molecule connexin-45 (Cx45; GJC1) in lymphatic endothelium were not previously known. We found that Cx45 was expressed widely in the endothelium of murine lymphatics, in both valve and nonvalve regions. Cell-specific deletion of Cx45, driven by a constitutive Cre line (Lyve1-Cre) or an inducible Cre line (Prox1-CreERT2), compromised the function of lymphatic valves, as assessed by physiological tests (back leak and closure) of isolated, single-valve vessel segments.

PROX1 Inhibits PDGF-B Expression to Prevent Myxomatous Degeneration of Heart Valves.

Background: Cardiac valve disease is observed in 2.5% of the general population and 10% of the elderly people. Effective pharmacological treatments are currently not available, and patients with severe cardiac valve disease require surgery.

One-year follow-up of a multifocal intraocular lens with optimized elevated phase shift.

Purpose: To evaluate the standard outcomes of a multifocal intraocular lens (mIOL) with optimized elevated phase shift (EPS).

Setting: Qvision, Ophthalmology Department, VITHAS Almería, Spain.

Design: Retrospective observational.

Evolution of operating microscopes and development of 3D visualization systems for intraocular surgery.

The recent development of high-resolution, heads-up, 3D visualization microscopy systems has provided new technical and visualization options for ophthalmic surgeons. In this review, we explore the evolution of microscope technologies, the science behind modern 3D visualization microscopy systems, and the practical benefits (as well as disadvantages) that these systems provide over conventional microscopes for intraocular surgical practice. Overall, modern 3D visualization systems reduce the requirements for artificial illumination and provide enhanced visualization and resolution of ocular structures, improving ergonomics, and facilitating a superior educational experience.

Approach to a spontaneously ruptured posterior polar cataract.

A 61-year-old man presented with gradual blurring of vision and glare in both eyes for a couple of years, with worsening of the vision in his right eye over the past 2 months. He had no medical history of note. On clinical examination, his visual acuities were 20/80 in the right eye and 20/30 in the left eye, uncorrected.

Promoting Lymphangiogenesis and Lymphatic Growth and Remodeling to Treat Cardiovascular and Metabolic Diseases.

Lymphatic vessels are low-pressure, blind-ended tubular structures that play a crucial role in the maintenance of tissue fluid homeostasis, immune cell trafficking, and dietary lipid uptake and transport. Emerging research has indicated that the promotion of lymphatic vascular growth, remodeling, and function can reduce inflammation and diminish disease severity in several pathophysiologic conditions. In particular, recent groundbreaking studies have shown that lymphangiogenesis, which describes the formation of new lymphatic vessels from the existing lymphatic vasculature, can be beneficial for the alleviation and resolution of metabolic and cardiovascular diseases.

GATA2 regulates blood/lymph separation in a platelet-dependent and lymphovenous valve-independent manner.

Introduction: Lymphatic vessels collect interstitial fluid, immune cells, and digested lipids and return these bodily fluids to blood through two pairs of lymphovenous valves (LVVs). Like other cardiovascular valves LVVs prevent the backflow of blood into the lymphatic vessels. In addition to LVVs, platelets are necessary to prevent the entry of blood into the lymphatic vessels.

Molecular Mechanisms Driving Lymphedema and Other Lymphatic Anomalies.

Lymphatic vasculature regulates fluid homeostasis by absorbing interstitial fluid and returning it to blood. Lymphatic vasculature is also critical for lipid absorption and inflammatory response. Lymphatic vasculature is composed of lymphatic capillaries, collecting lymphatic vessels, lymphatic valves, and lymphovenous valves.

Whole-mount Immunohistochemistry to Visualize Mouse Embryonic Dermal Lymphatic Vasculature.

Lymphatic vessels are abundant in the skin where they regulate interstitial fluid uptake and immune surveillance. Defects in dermal lymphatic vessels, such as fewer vessels and abnormal lymphatic vessel coverage with mural cells, are frequently associated with lymphedema and other lymphatic disorders. Whole-mount immunohistochemistry allows the visualization of dermal lymphatic vessels and identifies morphogenetic defects.

Activation of Crtc2/Creb1 in skeletal muscle enhances weight loss during intermittent fasting.

The Creb-Regulated Transcriptional Coactivator (Crtc) family of transcriptional coregulators drive Creb1-mediated transcription effects on metabolism in many tissues, but the in vivo effects of Crtc2/Creb1 transcription on skeletal muscle metabolism are not known. Skeletal muscle-specific overexpression of Crtc2 (Crtc2 mice) induced greater mitochondrial activity, metabolic flux capacity for both carbohydrates and fats, improved glucose tolerance and insulin sensitivity, and increased oxidative capacity, supported by upregulation of key metabolic genes. Crtc2 overexpression led to greater weight loss during alternate day fasting (ADF), selective loss of fat rather than lean mass, maintenance of higher energy expenditure during the fast and reduced binge-eating during the feeding period.

Dual-mechanism estrogen receptor inhibitors.

Efforts to improve estrogen receptor-α (ER)-targeted therapies in breast cancer have relied upon a single mechanism, with ligands having a single side chain on the ligand core that extends outward to determine antagonism of breast cancer growth. Here, we describe inhibitors with two ER-targeting moieties, one of which uses an alternate structural mechanism to generate full antagonism, freeing the side chain to independently determine other critical properties of the ligands. By combining two molecular targeting approaches into a single ER ligand, we have generated antiestrogens that function through new mechanisms and structural paradigms to achieve antagonism.