Adipogenesis : a complex interplay of multiple molecular determinants and pathways

The formation of adipocytes during embryogenesis has been largely understudied. However, preadipocytes appear to originate from multipotent mesenchymal stromal/stem cells which migrate from the mesoderm to their anatomical localization. Most studies on adipocyte formation (adipogenesis) have used preadipocytes derived from adult stem/stromal cells. Adipogenesis consists of two phases, namely commitment and terminal di erentiation. This review discusses the role of signalling pathways, epigenetic modifiers, and transcription factors in preadipocyte commitment and di erentiation into mature adipocytes, as well as limitations in our understanding of these processes. To date, a limited number of transcription factors, genes and signalling pathways have been described to regulate preadipocyte commitment. One reason could be that most studies on adipogenesis have used preadipocytes already committed to the adipogenic lineage, which are therefore not suitable for studying preadipocyte commitment. Conversely, over a dozen molecular players including transcription factors, genes, signalling pathways, epigenetic regulators, and microRNAs have been described to be involved in the di erentiation of preadipocytes to adipocytes; however, only peroxisome proliferator-activated receptor gamma has proven to be clinically relevant. Adetailed understanding of how the molecular players underpinning adipogenesis relate to adipose tissue function could provide new therapeutic approaches for addressing obesity without compromising adipose tissue function.The South African Medical Research Council University Flagship Project, the SAMRC Extramural Unit for Stem Cell Research and Therapy, the Institute for Cellular and Molecular Medicine of the University of Pretoria, the South African National Research Foundation and National Health Laboratory Services.http://www.mdpi.com/journal/ijmsam2020ImmunologyOral Pathology and Oral Biolog

Geospatial Resolution of Human and Bacterial Diversity with City-Scale Metagenomics

The panoply of microorganisms and other species present in our environment influence human health and disease, especially in cities, but have not been profiled with metagenomics at a city-wide scale. We sequenced DNA from surfaces across the entire New York City (NYC) subway system, the Gowanus Canal, and public parks. Nearly half of the DNA (48%) does not match any known organism; identified organisms spanned 1,688 bacterial, viral, archaeal, and eukaryotic taxa, which were enriched for harmless genera associated with skin (e.g., Acinetobacter). Predicted ancestry of human DNA left on subway surfaces can recapitulate U.S. Census demographic data, and bacterial signatures can reveal a station’s history, such as marine-associated bacteria in a hurricane-flooded station. Some evidence of pathogens was found (Bacillus anthracis), but a lack of reported cases in NYC suggests that the pathogens represent a normal, urban microbiome. This baseline metagenomic map of NYC could help long-term disease surveillance, bioterrorism threat mitigation, and health management in the built environment of citie

The impact of obesity on the cellular and molecular pathophysiology of COVID-19

Emerging evidence reveals a strong association between COVID-19 and obesity in terms of disease severity, need for hospitalisation and risk of mortality. In this review, we discuss cellular and molecular mechanisms potentially contributing to the pathophysiology of COVID-19 in obese patients. Understanding the relationship between COVID-19 and obesity is pertinent for the clinical management of these patients.The South African Medical Research Council Extramural Unit for Stem Cell Research and Therapy, the Institute for Cellular and Molecular Medicine of the University of Pretoria (MSP); the South African National Research Foundation and University of Pretoria postgraduate bursaries.http://www.samj.org.zaam2021Immunolog

Nebulized Ketamine Used for Managing Ankle Fracture in the Prehospital Emergency Setting: A Case Report

Introduction: Acute traumatic limb injury is a common complaint of patients presenting to the emergency department (ED). Ketamine is an effective analgesic administered via intravenous (IV), intranasal (IN), intramuscular (IM), and nebulized routes in the ED. It has also been used in the prehospital setting via IV, IM, and IN routes. Recent studies have proposed the prehospital use of nebulized ketamine via breath-actuated nebulizer (BAN) as a noninvasive and effective method of analgesic delivery, as well as an alternative to opioid analgesia.Case Report: We present a case of a patient with right ankle fracture after a 12-foot fall who subsequently received 0.75 milligrams per kilogram of nebulized ketamine via BAN in the prehospital setting. The patient reported improvement of pain from 8/10 to 3/10 on the pain scale without need for additional pain medication during prehospital transport. This report supports the use of nebulized ketamine via BAN in the prehospital setting for acute traumatic limb injuries.Conclusion: The use of nebulized ketamine via BAN in the prehospital setting may be an effective analgesic option for the management of patients with acute traumatic limb injuries, particularly in those with difficult IV access, where mucosal atomization devices are not accessible, or where opioid-sparing treatments are preferable

Sexual dimorphism in changes that occur in tissues, organs and plasma during the early stages of obesity development

Despite obesity being a major health concern, information on the early clinical changes that occur in plasma and tissues during obesity development and the influence of sexual dimorphism is lacking. This study investigated changes in tissue and organ histology, macrophage infiltration, plasma hormones, lipid, and chemokine and cytokine levels in mice fed on a high fat diet for 11- weeks. An increase in adiposity, accompanied by adipocyte hypertrophy and macrophage infiltration, was observed to be significantly greater in males than females. Important changes in cell morphology and histology were noted in the lungs, liver, kidney, spleen, and heart, which may indicate early signs for developing obesity associated comorbidities. Leptin, but not adiponectin, was significantly altered during weight gain. Additionally, leptin, but not adiposity, correlated with insulin levels. Interestingly, GM-CSF, TNFα, and IL-12 (p70) were not produced in the early stages of obesity development. Meanwhile, the production of MCP-1, IP-10, RANTES, IL-10, IL-6, KC, and IL-9 were greatly influenced by sexual dimorphism. Importantly, IL-6/IL-10 axis of anti-inflammatory cytokine regulation was observed only in females and may account for their significantly lower weight gain compared to males. This study provides new knowledge on how sexual dimorphism may influence the development of obesity and associated comorbidities.The South African National Research Foundation, the National Health Laboratory Services, the South African Medical Research Council University Flagship Project (SAMRC-RFA-UFSP-01-2013/STEM CELLS), the SAMRC Extramural Unit for Stem Cell Research and Therapy, and the Institute for Cellular and Molecular Medicine of the University of Pretoria.http://www.mdpi.com/journal/biologypm2021ImmunologyOral Pathology and Oral Biolog