Mesothelial cells in tissue repair and fibrosis

Mesothelial cells are fundamental to the maintenance of serosal integrity and homeostasis and play a critical role in normal serosal repair following injury. However, when normal repair mechanisms breakdown, mesothelial cells take on a profibrotic role, secreting inflammatory, and profibrotic mediators, differentiating and migrating into the injured tissues where they contribute to fibrogenesis. The development of new molecular and cell tracking techniques has made it possible to examine the origin of fibrotic cells within damaged tissues and to elucidate the roles they play in inflammation and fibrosis. In addition to secreting proinflammatory mediators and contributing to both coagulation and fibrinolysis, mesothelial cells undergo mesothelial-to-mesenchymal transition, a process analogous to epithelial-to-mesenchymal transition, and become fibrogenic cells. Fibrogenic mesothelial cells have now been identified in tissues where they have not previously been thought to occur, such as within the parenchyma of the fibrotic lung. These findings show a direct role for mesothelial cells in fibrogenesis and open therapeutic strategies to prevent or reverse the fibrotic process

Research of working area development parameters in conditions of deep steep deposit finalizing

Отримано формули розрахунку об’єму запасів корисних копалин в приконтурній та глибинній зоні. Встановлено характер впливу параметрів доробки глибоких крутоспадних родовищ відкритим способом на доцільне положення поточних та проектних контурів кар’єру. Встановлено, що найменший середній коефіцієнт розкриву досягається при мінімальному значенні суми обсягів корисної копалини приконтурної зони лежачого і висячого боків покладу в проектному положенні. Найменший поточний коефіцієнт розкриву досягається при мінімальному значенні суми обсягів корисної копалини приконтурної зони лежачого і висячого боків покладу, а також робочого борту кар'єру в поточному положенні

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Structure and function of the mesothelial cell

This chapter describes the morphology and structure of the mesothelium and discusses some of the many roles mesothelial cells play under normal and pathological conditions. Mesothelial cells form a monolayer of cobblestone-like cells that line the peritoneal, pleural, and pericardial cavities and most internal organs. Under normal conditions, mesothelial cells form a monolayer, and play important roles in maintaining normal serosal membrane integrity and function. Mesothelial cells are unique in that they function as an epithelium but express both epithelial and mesenchymal markers and have an inherent ability to undergo Epithelial to mesenchymal transition (EMT), a process that has recently been termed mesothelial to mesenchymal transition (MMT). MMT is proposed to play a role in the establishment of endometriosis where retrograde menstrual tissue embeds on the peritoneal surface and forms an active lesion. The processes that occur during pathological EMT are thought to be comparable to physiological EMT as they are controlled by similar signaling pathway regulators and effector molecules

Mesothelial cells and peritoneal homeostasis

The mesothelium was traditionally thought to be a simple tissue with the sole function of providing a slippery, nonadhesive, and protective surface to allow easy movement of organs within their body cavities. However, our knowledge of mesothelial cell physiology is rapidly expanding, and the mesothelium is now recognized as a dynamic cellular membrane with many other important functions. When injured, mesothelial cells initiate a cascade of processes leading either to complete regeneration of the mesothelium or the development of pathologies such as adhesions. Normal mesothelial healing is unique in that, unlike with other epithelial-like surfaces, healing appears diffusely across the denuded surface, whereas for epithelium healing occurs solely at the wound edges. This is because of a free-floating population of mesothelial cells which attach to the injured serosa. Taking advantage of this phenomenon, intraperitoneal injections of mesothelial cells have been assessed for their ability to prevent adhesion formation. This review discusses some of the functions of mesothelial cells regarding maintenance of serosal integrity and outlines the mechanisms involved in mesothelial healing. In addition, the pathogenesis of adhesion formation is discussed with particular attention to the potential role of mesothelial cells in both preventing and inducing their development

The Origin of Regenerating Mesothelium: A Historical Perspective

Bichat first described the mesothelium in 1827 but despite its early discovery, it has only been in recent years that its importance both in health and disease has been realised. One area still poorly understood is that of the mechanisms regulating mesothelial repair. Mesothelial cells are derived from the mesoderm but express many epithelial characteristics. However, mesothelium does not heal in the same way as other epithelial-like cells. Epithelium heals by centripetal migration, with cells at the edge of the wound proliferating and migrating into the injured area. Hertzler in 1919 noted that both large and small peritoneal injuries healed within the same time frame, concluding that the mesothelium could not heal solely by centripetal migration. The exact mechanisms involved in mesothelial regeneration following injury are controversial with a number of proposals suggested to explain the origin of the regenerating cells. This review will examine these proposals and give some insights into the likely mechanisms involved