FNDC5/Irisin: Physiology and Pathophysiology.

A sedentary lifestyle or lack of physical activity increases the risk of different diseases, including obesity, diabetes, heart diseases, certain types of cancers, and some neurological diseases. Physical exercise helps improve quality of life and reduces the risk of many diseases. Irisin, a hormone induced by exercise, is a fragmented product of FNDC5 (a cell membrane protein) and acts as a linkage between muscles and other tissues. Over the past decade, it has become clear that irisin is a molecular mimic of exercise and shows various beneficial effects, such as browning of adipocytes, modulation of metabolic processes, regulation of bone metabolism, and functioning of the nervous system. Irisin has a role in carcinogenesis; numerous studies have shown its impact on migration, invasion, and proliferation of cancer cells. The receptor of irisin is not completely known; however, in some tissues it probably acts via a specific class of integrin receptors. Here, we review research from the past decade that has identified irisin as a potential therapeutic agent in the prevention or treatment of various metabolic-related and other diseases. This article delineates structural and biochemical aspects of irisin and provides an insight into the role of irisin in different pathological conditions.

Heart failure impairs the mechanotransduction properties of human cardiac pericytes.

The prominent impact that coronary microcirculation disease (CMD) exerts on heart failure symptoms and prognosis, even in the presence of macrovascular atherosclerosis, has been recently acknowledged. Experimental delivery of pericytes in non-revascularized myocardial infarction improves cardiac function by stimulating angiogenesis and myocardial perfusion. Aim of this work is to verify if pericytes (Pc) residing in ischemic failing human hearts display altered mechano-transduction properties and to assess which alterations of the mechano-sensing machinery are associated with the observed impaired response to mechanical cues. RESULTS: Microvascular rarefaction and defects of YAP/TAZ activation characterize failing human hearts. Although both donor (D-) and explanted (E-) heart derived cardiac Pc support angiogenesis, D-Pc exert this effect significantly better than E-Pc. The latter are characterized by reduced focal adhesion density, decreased activation of the focal adhesion kinase (FAK)/ Crk-associated substrate (CAS) pathway, low expression of caveolin-1, and defective transduction of extracellular stiffness into cytoskeletal stiffening, together with an impaired response to both fibronectin and lysophosphatidic acid. Importantly, Mitogen-activated protein kinase kinase inhibition restores YAP/TAZ nuclear translocation. CONCLUSION: Heart failure impairs Pc mechano-transduction properties, but this defect could be reversed pharmacologically.

Role of CD20+ T cells in cancer, autoimmunity and obesity.

Despite the known link between obesity and insulin resistance (IR) to chronic low-grade inflammation, new markers capable of early IR detection are needed. Immune cells are components of adipose tissue's (AT) stromal vascular fraction (SVF) that regulate AT homeostasis. The altered phenotype and function of AT-infiltrating immune cells may contribute to the development and maintenance of local AT inflammation observed under obesity-induced IR conditions. Impaired AT-specific immunometabolic function may influence the whole organism. Therefore, AT-infiltrating immune cells may be important players in the development of obesity-related metabolic complications, such as type 2 diabetes mellitus (T2DM). B and T cells, particularly CD20+ T cells, play important roles in human pathology, such as autoimmune disease and cancer. However, the question remains as to whether CD20+ T cells have an important contribution to the development of obesity-related IR. While circulating CD20+ T cells are mostly of the central memory phenotype (i.e. antigen-experienced T cells with the ability to home to secondary lymphoid organs), tissues-infiltrated CD20+ T cells are predominantly of the effector memory phenotype (i.e. antigen-experienced T cells that preferentially infiltrate peripheral tissues). The latter produce pro-inflammatory cytokines, such as IFN-γ and IL-17, which play a role in obesity-related IR development. This review describes the CD20 molecule and its presence in both B and T cells, shedding light on its ontogeny and function, in health and disease, with emphasis on AT. The link between CD20+ T cell dysregulation, obesity, and IR development supports the role of CD20+ T cells as markers of adipose tissue dysmetabolism.

Clinical and Laboratory Diagnosis of Antiphospholipid Syndrome: A Review.

The antiphospholipid syndrome (APS) manifests through venous or arterial thrombosis, with or without pregnancy complication alongside the continuous presence of antiphospholipid antibodies (aPL). APS classification relies on three aPL subtypes: anticardiolipin (aCL), anti-ß2-glycoprotein I antibodies (anti-ß2GPI), and lupus anticoagulants (LA) antibodies. Given that thrombosis and pregnancy issues are not unique to APS, the precise and reliable identification of aPL forms the basis for diagnosis. Semi-quantitative solid-phase assays identify two antibodies, aCL and anti-ß2GPI, while LA detection occurs through various phospholipid-dependent coagulation assays that are based on antibody behaviour. LA, specifically, is conclusively associated with thrombosis, prompting discussions around the serological criteria for APS. Despite advancements in LA detection, the standardisation of all aPL detection assays remains imperative. The combined presence of aCL and anti-ß2GPI with thrombosis inconsistently triggers concern. Initial presentations by APS patients commonly exhibit a heightened risk of stroke, miscarriages in the later stages of pregnancy, positive results of LA tests, and widespread thrombosis across multiple organs, often leading to adverse outcomes. Correctly diagnosing this condition is pivotal to avoid unnecessary long-term secondary thromboprophylaxis.

Genome-scale models as a vehicle for knowledge transfer from microbial to mammalian cell systems.

With the plethora of omics data becoming available for mammalian cell and, increasingly, human cell systems, Genome-scale metabolic models (GEMs) have emerged as a useful tool for their organisation and analysis. The systems biology community has developed an array of tools for the solution, interrogation and customisation of GEMs as well as algorithms that enable the design of cells with desired phenotypes based on the multi-omics information contained in these models. However, these tools have largely found application in microbial cells systems, which benefit from smaller model size and ease of experimentation. Herein, we discuss the major outstanding challenges in the use of GEMs as a vehicle for accurately analysing data for mammalian cell systems and transferring methodologies that would enable their use to design strains and processes. We provide insights on the opportunities and limitations of applying GEMs to human cell systems for advancing our understanding of health and disease. We further propose their integration with data-driven tools and their enrichment with cellular functions beyond metabolism, which would, in theory, more accurately describe how resources are allocated intracellularly.

An eLearning module is comparable to face-to-face teaching in a nursing human pathophysiology subject.

BACKGROUND: Human pathophysiology is important in undergraduate nursing education to help students develop clinical reasoning skills. Traditionally pathophysiology education in undergraduate nursing is taught face-to-face. However, eLearning in nursing curricula may provide flexible delivery options. OBJECTIVE: With increased inclusion of technology enhanced learning in nursing curricula, a hematology eLearning module was evaluated in a pathophysiology subject to determine whether it was comparable to face-to-face learning. DESIGN: Single-blind randomized pre-test/post-test controlled trial. SETTING: School of Health and Behavioural Sciences, University of the Sunshine Coast. PARTICIPANTS: A total of 271 second-year undergraduate students enrolled in Human Pathophysiology were included in the study. Students were from three bachelor programs: Nursing Science; Paramedic Science; and Clinical Exercise Physiology. Students were randomly allocated to either the experimental group (n = 85) or the control group (n = 186). METHODS: A hematology eLearning module was designed to be self-directed and learner-centered, guided by constructivist learning theories for delivery in the human pathophysiology subject. The experimental "eLearning" group completed the module independently, and the control "face-to-face" group completed equivalent paper-based activities facilitated by a tutor. All students completed a pre-test assessment and two post-test assessments two weeks after the intervention and at the end of the subject. RESULTS: There was no significant difference in assessment scores between the experimental and control groups, or between nursing and other programs. CONCLUSION: eLearning was comparable to face-to-face teaching in this study. We recommend further research to strengthen the links between pathophysiology theory to clinical reasoning skills using eLearning.

Role of Selective Sodium-Glucose Co-Transporter-2 Inhibitors in Managing Cardio-Renal Complications in Type 2 Diabetes Mellitus: Beyond Glycemic Control.

Chronic kidney disease (CKD) and cardiovascular complications are the leading causes of death in type 2 diabetes mellitus. Apart from the standard therapy, which includes angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), lipid-lowering medication, and anti-platelet therapy, the new group of drugs termed the 'sodium-glucose co-transporter-2 (SGLT2) inhibitors' have shown promising results in managing complications arising from the cardiovascular and renal systems in diabetics. This article attempts to highlight the role and mechanism of action of this class of drugs.   We reviewed 127 articles and analyses of randomized controlled trials using several drugs in the SGLT2 inhibitor family (sotagliflozin, canagliflozin, dapagliflozin, tofogliflozin) over the past five years, out of which 58 met the criteria and aim of the study. These articles were retrieved from PubMed, Google Scholar, and Medline data sources and assessed for quality using the assessment of multiple systematic reviews (AMSTAR) checklist and Cochrane risk-of-bias tool. Results from the review showed significant benefits in reducing progressive renal decline, blood pressure control, heart failure hospitalization, death from renal or cardiovascular complications, myocardial infarction, and stroke. This benefit is also seen in non-diabetic patients, hence postulating that these effects may not be solely due to glycemic control. There are several mechanisms with which it achieves this benefit with the most significant being its role on intraglomerular pressure. Other pathways include blood pressure control, natriuresis, ventricular remodeling, erythropoiesis, lipid metabolism, plasma volume, and electrolyte imbalance.   It is clear that the role of SGLT2 inhibitors isn't limited to glycemic control and they can achieve a wide array of functions by affecting different systems. More studies need to be done to completely understand this medication to improve the quality of life in diabetic and non-diabetic patients living with CKD and cardiovascular complications. The pharmacokinetics of this drug could also help set the basis for newer medications.

Is COVID-19 Similar in Pregnant and Non-Pregnant Women?

Approximately one-third of infected pregnant women died from severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemics of the past two decades. It is logical to predict that pregnant women infected with the novel coronavirus (SARS-CoV-2) might be at higher risk for severe illness, morbidity, or mortality compared with non-pregnant women. However, a review of the literature indicates that pregnant women are not more likely to be seriously ill than other healthy non-pregnant women if they develop coronavirus disease (COVID-19). This observation begs the question: "Why does pregnancy not increase the risk for acquiring SARS-CoV-2 infection, nor does it worsen the clinical course of COVID-19 compared with non-pregnant individuals?" Herein, we try to explain our observations when considering whether the immunologic changes of pregnancy and other physiologic adaptations of pregnancy affect the virulence and course of SARS-CoV-2 infection.