Prevention of what

Adipose tissue plays essential roles in maintaining lipid and glucose homeostasis. To date several types of adipose tissue have been identified, namely white, brown, and beige, that reside in various specific anatomical locations throughout the body. The cellular composition, secretome, and location of these adipose depots define their function in health and metabolic disease. In obesity, adipose tissue becomes dysfunctional, promoting a pro-inflammatory, hyperlipidemic and insulin resistant environment that contributes to type 2 diabetes mellitus (T2DM). Concurrently, similar features that result from adipose tissue dysfunction also promote cardiovascular disease (CVD) by mechanisms that can be augmented by T2DM. The mechanisms by which dysfunctional adipose tissue simultaneously promote T2DM and CVD, focusing on adipose tissue depot-specific adipokines, inflammatory profiles, and metabolism, will be the focus of this review. The impact that various T2DM and CVD treatment strategies have on adipose tissue function and body weight also will be discussed.

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Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease.

Irisin is a myokine that leads to increased energy expenditure by stimulating the 'browning' of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. Consequently, several studies attempted to characterize the role of irisin in glucose regulation, but contradictory results have been reported, and even the existence of this hormone has been questioned. In this Review, we present the current knowledge on the physiology of irisin and its role in glucose homeostasis. We describe the mechanisms involved in the synthesis, secretion, circulation and regulation of irisin, and the controversies regarding the measurement of irisin. We also discuss the direct effects of irisin on glucose regulatory mechanisms in different organs, the indirect effects and interactions with other hormones, and the important open questions with regard to irisin in those organs. Finally, we present the results from animal interventional studies and from human clinical studies investigating the association of irisin with obesity, insulin resistance, type 2 diabetes mellitus and the metabolic syndrome.

Physiology and role of irisin in glucose homeostasis

There is compelling evidence to support an aetiological role for inflammation, oxidative and nitrosative stress (O&NS), and mitochondrial dysfunction in the pathophysiology of major neuropsychiatric disorders, including depression, schizophrenia, bipolar disorder, and Alzheimer's disease (AD). These may represent new pathways for therapy. Aspirin is a non-steroidal anti-inflammatory drug that is an irreversible inhibitor of both cyclooxygenase (COX)-1 and COX-2, It stimulates endogenous production of anti-inflammatory regulatory 'braking signals', including lipoxins, which dampen the inflammatory response and reduce levels of inflammatory biomarkers, including C-reactive protein, tumor necrosis factor-α and interleukin (IL)--6, but not negative immunoregulatory cytokines, such as IL-4 and IL-10. Aspirin can reduce oxidative stress and protect against oxidative damage. Early evidence suggests there are beneficial effects of aspirin in preclinical and clinical studies in mood disorders and schizophrenia, and epidemiological data suggests that high-dose aspirin is associated with a reduced risk of AD. Aspirin, one of the oldest agents in medicine, is a potential new therapy for a range of neuropsychiatric disorders, and may provide proof-of-principle support for the role of inflammation and O&NS in the pathophysiology of this diverse group of disorders.

http://dro.deakin.edu.au/eserv/DU:30052827/berk-aspirinareview-2013.pdf

Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness

Endothelial cells, as well as their major products nitric oxide (NO) and prostacyclin, play a key role in the regulation of vascular homeostasis. Diabetes mellitus is an important risk factor for cardiovascular disease. Diabetes-induced endothelial dysfunction is a critical and initiating factor in the genesis of diabetic vascular complications. The present review focuses on both large blood vessels and the microvasculature. The endothelial dysfunction in diabetic macrovascular complications is characterized by reduced NO bioavailability, poorly compensated for by increased production of prostacyclin and/or endothelium-dependent hyperpolarizations, and increased production or action of endothelium-derived vasoconstrictors. The endothelial dysfunction of microvascular complications is primarily characterized by decreased release of NO, enhanced oxidative stress, increased production of inflammatory factors, abnormal angiogenesis, and impaired endothelial repair. In addition, non-coding RNAs (microRNAs) have emerged as participating in numerous cellular processes. Thus, this reviews pays special attention to microRNAs and their modulatory role in diabetes-induced vascular dysfunction. Some therapeutic strategies for preventing and restoring diabetic endothelial dysfunction are also highlighted.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/1753-0407.12521

Macro- and microvascular endothelial dysfunction in diabetes

Role of dysfunctional peri-organ adipose tissue in metabolic disease.

Lung cancer is a fatal disease with high morbidity and mortality. As a major type of non-small cell lung cancer (NSCLC), lung adenocarcinoma (LUAD) has come into the focus of the biological and clinical research. Nevertheless, potential functions of N6-methyladenosine (m6A) methylation-related long non-coding RNAs (lncRNAs) in the tumor immune microenvironment (TIME) remain unclear. Here, we analyzed RNA-seq data of 522 samples from the TCGA-LUAD project. Based on integrative analyses of lncRNA, immune, and clinical profiles, we developed a computational method to determine the characteristics of lncRNAs as an indicators of immune cell infiltration in LUAD patients. Subsequently, we investigated the influence of m6A-related lncRNAs on prognosis and immunotherapy in patients with LUAD. We identified 24 m6A-related lncRNAs that were related to LUAD prognosis and clustered in two molecular subtypes (clusters 1 and 2). Our results suggest that cluster 1 was significantly related to downregulation of PD-L1, enhancement of immune cell infiltration, and good prognosis. Furthermore, p53 and mTOR pathways were enriched in cluster 1, whereas in the cluster 2, PPAR was uncommonly enriched. Patients with LUAD who had lower risk scores exhibited higher immunoscores and lower expression levels of programmed cell death-ligand 1, compared with patients who had higher risk scores. Finally, m6A-related lncRNAs were implicated in the TIME; our findings indicate that these lncRNAs are critical within the TIME in LUAD. These signatures are promising as potential targets for improved LUAD immunotherapy.

Comprehensive Analysis of Tumor Immune Microenvironment and Prognosis of m6A-Related IncRNAs in Lung Adenocarcinoma.

Lung cancer is the most common and deadliest type of cancer worldwide. Research concerning lung cancer has made considerable progress in recent decades, but lung cancer remains the leading cause of malignancy-related mortality rate. Mesenchymal stem cells (MSCs) mainly exist in fat, umbilical cord blood, bone marrow, bone, and muscle. MSCs are a primary component of the tumor microenvironment (TME). Recent studies have shown that MSCs have roles in lung cancer-related proliferation, invasion, migration, and angiogenesis, but the underlying mechanisms are poorly understood. Because MSCs can migrate to the TME, there is increasing attention toward the use of MSCs in drugs or gene vectors for cancer treatment. This review summarizes the roles and effects of MSCs in lung cancer, while addressing clinical applications of MSCs in lung cancer treatment.

Advances in Understanding the Roles of Mesenchymal Stem Cells in Lung Cancer.

Aims: Pancreatic cancer (PC) is a malignant tumor with a strong invasive nature and low survival rate. We aimed to estimate the PC burden at the global, regional, and national levels in 204 countries from 1990 to 2019. Methods: Detailed data, including the incidence, death, and disability-adjusted life years (DALYs), were analyzed from the Global Burden of Diseases Study 2019. Results: Globally, there were 530,297 (486,175–573,635) incident cases and 531,107 (491,948–566,537) deaths from PC in 2019. The age-standardized incidence rate (ASIR) was 6.6 (6–7.1), and the age-standardized mortality rate (ASMR) was 6.6 (6.1–7.1) per 100,000 person-years. PC caused 11,549,016 (10,777,405–12,338,912) DALYs, with an age-standardized rate of 139.6 (130.2–149.1) per 100,000 person-years. There were increases in estimated annual percentage changes (EAPCs) of ASIR (0.83; 0.78–0.87), ASMR (0.77; 0.73–0.81), and age-standardized DALYs rate (ASDR) (0.67; 0.63–0.71). The global number of incident cases increased by 168.7%, from 197,348 (188,604–203,971) to 530,297 (486,175–573,635); the number of deaths increased by 168.2% from 198,051 (189,329–204,763) to 531,107 (491,948–566,537); and total DALYs increased by 148.5% from 4,647,207 (4,465,440–4,812,129) to 11,549,016 (10,777,405–12,338,912). East Asia and China recorded the highest number of incident cases, deaths, and DALYs. The proportion of deaths was attributable to smoking (21.4%), elevated fasting glucose (9.1%), and high BMI (6%). Conclusions: Our study updated the epidemiological trends and risk factors for PC. PC remains a major hazard to the sustainability of health systems worldwide, with an increasing incidence rate and mortality from 1990 to 2019. More targeted strategies are required to prevent and treat PC.

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Fang Han

Papers

Role of dysfunctional peri-organ adipose tissue in metabolic disease.

Comprehensive Analysis of Tumor Immune Microenvironment and Prognosis of m6A-Related IncRNAs in Lung Adenocarcinoma.

Advances in Understanding the Roles of Mesenchymal Stem Cells in Lung Cancer.

Global, Regional, and National Burden of Pancreatic Cancer, 1990–2019: Results from the Global Burden of Disease Study 2019

Astrocytes in Post-Stroke Depression: Roles in Inflammation, Neurotransmission, and Neurotrophin Signaling.