Project description:Platelets (small, anucleate cell fragments) derive from large precursor cells, megakaryocytes (MKs), that reside in the bone marrow. MKs emerge from hematopoietic stem cells in a complex differentiation process that involves cytoplasmic maturation, including the formation of the demarcation membrane system, and polyploidization. The main function of MKs is the generation of platelets, which predominantly occurs through the release of long, microtubule-rich proplatelets into vessel sinusoids. However, the idea of a 1-dimensional role of MKs as platelet precursors is currently being questioned because of advances in high-resolution microscopy and single-cell omics. On the one hand, recent findings suggest that proplatelet formation from bone marrow-derived MKs is not the only mechanism of platelet production, but that it may also occur through budding of the plasma membrane and in distant organs such as lung or liver. On the other hand, novel evidence suggests that MKs not only maintain physiological platelet levels but further contribute to bone marrow homeostasis through the release of extracellular vesicles or cytokines, such as transforming growth factor β1 or platelet factor 4. The notion of multitasking MKs was reinforced in recent studies by using single-cell RNA sequencing approaches on MKs derived from adult and fetal bone marrow and lungs, leading to the identification of different MK subsets that appeared to exhibit immunomodulatory or secretory roles. In the following article, novel insights into the mechanisms leading to proplatelet formation in vitro and in vivo will be reviewed and the hypothesis of MKs as immunoregulatory cells will be critically discussed.

| S-EPMC9164737 | biostudies-literature

Don't Forget about Facilitatory Effects of Corticosteroids on β<sub>2</sub>-Adrenoceptors in Acute Asthma.

Project description: Not available

| S-EPMC7737594 | biostudies-literature

Don't forget astrocytes when targeting Alzheimer's disease.

Project description:Astrocytes are essential for CNS health, regulating homeostasis, metabolism, and synaptic transmission. In addition to these and many other physiological roles, the pathological impact of astrocytes ("reactive astrocytes") in acute trauma and chronic disease like Alzheimer's disease (AD) is well established. Growing evidence supports a fundamental and active role of astrocytes in multiple neurodegenerative diseases. With a growing interest in normal astrocyte biology, and countless studies on changes in astrocyte function in the context of disease, it may be a surprise that no therapies exist incorporating astrocytes as key targets. Here, we examine unintentional effects of current AD therapies on astrocyte function and theorize how astrocytes may be intentionally targeted for more efficacious therapeutic outcomes. Given their integral role in normal neuronal functioning, incorporating astrocytes as key criteria for AD drug development can only lead to more effective therapies for the millions of AD sufferers worldwide. LINKED ARTICLES: This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc.

| S-EPMC6715613 | biostudies-literature

Albumin Substitution in Decompensated Liver Cirrhosis: Don't Forget Zinc.

Project description:Decompensated liver cirrhosis has a dismal prognosis, with patients surviving on average for 2-4 years after the first diagnosis of ascites. Albumin is an important tool in the therapy of cirrhotic ascites. By virtue of its oncotic properties, it reduces the risk of cardiovascular dysfunction after paracentesis. Treatment with albumin also counteracts the development of hepatorenal syndrome and spontaneous bacterial peritonitis. More recently, the positive impact of long-term albumin supplementation in liver disease, based on its pleiotropic non-oncotic activities, has been recognized. These include transport of endo- and exogenous substances, anti-inflammatory, antioxidant and immunomodulatory activities, and stabilizing effects on the endothelium. Besides the growing recognition that effective albumin therapy requires adjustment of the plasma level to normal physiological values, the search for substances with adjuvant activities is becoming increasingly important. More than 75% of patients with decompensated liver cirrhosis do not only present with hypoalbuminemia but also with zinc deficiency. There is a close relationship between albumin and the essential trace element zinc. First and foremost, albumin is the main carrier of zinc in plasma, and is hence critical for systemic distribution of zinc. In this review, we discuss important functions of albumin in the context of metabolic, immunological, oxidative, transport, and distribution processes, alongside crucial functions and effects of zinc and their mutual dependencies. In particular, we focus on the major role of chronic inflammatory processes in pathogenesis and progression of liver cirrhosis and how albumin therapy and zinc supplementation may affect these processes.

| S-EPMC8618355 | biostudies-literature

Don't forget the hip! Hip arthritis masquerading as knee pain.

Project description:BackgroundHip osteoarthritis typically manifests with groin or thigh pain. Other atypical pain patterns, including knee pain, have been described. Except for 2 case reports, there is no literature on this subject.MethodsFrom our institutional database, between 2011 and 2016, we identified 21 patients who were referred for treatment of knee pain but ultimately diagnosed with hip pathology as the cause of their pain. This group was evaluated for duration of symptoms prior to diagnosis, previous interventions, presence of walking aids, and symptom resolution after treatment of the hip pathology.ResultsFifteen of the 21 patients were referred from musculoskeletal providers (12 from orthopaedic surgeons). Prior to diagnosis of the hip etiology, 16 patients were reduced to major assistive devices including wheelchairs. Twelve of 21 patients had undergone surgical knee interventions, including total knee arthroplasty, with minimal to no relief of their pain. Seventeen of 21 referred patients underwent total hip arthroplasty at our institution. Fourteen patients had complete resolution of knee pain after total hip arthroplasty.ConclusionsAlthough knee pain referred from hip disease may be considered a basic and common knowledge, it continues to be an overlooked phenomenon. Most of the cases were misdiagnosed by musculoskeletal providers including orthopaedic surgeons and this highlights the need for continued education and awareness of this clinical scenario.

| S-EPMC5859208 | biostudies-literature

Before progressing from "exomes" to "genomes"… don't forget splicing variants.

Project description: Not available

| S-EPMC6189206 | biostudies-literature

Patient Registries in Idiopathic Pulmonary Fibrosis: Don't Forget Socioeconomic Status.

Project description: Not available

| S-EPMC7159425 | biostudies-literature