30 research outputs found

    Perivascular Adipose Tissue and Cardiometabolic Disease

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    BACKGROUND: Obesity is associated with insulin resistance, hypertension, and cardiovascular disease, but the mechanisms underlying these associations are incompletely understood. Microvascular dysfunction may play an important role in the pathogenesis of both insulin resistance and hypertension in obesity.CONTENT: Perivascular adipose tissue (PVAT) is a local deposit of adipose tissue surrounding the vasculature. PVAT is present throughout the body and has been shown to have a local effect on blood vessels. The influence of PVAT on the vasculature changes with increasing adiposity. PVAT similarly to other fat depots, is metabolically active, secreting a wide array of bioactive substances, termed ‘adipokines'. Adipokines include cytokines, chemokines and hormones that can act in a paracrine, autocrine or endocrine fashion. Many of the proinflammatory adipokines upregulated in obesity are known to influence vascular function, including endothelial function, oxidative stress, vascular stiffness and smooth muscle migration. Adipokines also stimulate immune cell migration into the vascular wall, potentially contributing to the inflammation found in atherosclerosis. Finally, adipokines modulate the effect of insulin on the vasculature, thereby decreasing insulin-mediated muscle glucose uptake. This leads to alterations in nitric oxide signaling, insulin resistance and potentially atherogenesis.SUMMARY: PVAT surrounds blood vessels. PVAT and the adventitial layer of blood vessels are in direct contact with each other. Healthy PVAT secretes adipokines and regulates vascular function. Obesity is associated with changes in adipokine secretion and the resultant inflammation of PVAT. The dysregulation of adipokines changes the effect of PVAT on the vasculature. Changes in perivascular adipokines secretion in obesity appear to contribute to the development of obesity-mediated vascular disease

    Identification of Biomarkers for Prostate Cancer

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    BACKGROUND: Prostate cancer (PCa) was the second most common type of cancer and the fifth leading cause of cancer-related death in men. The great challenge for physicians is being able to accurately predict PCa prognosis and treatment response in order to reduce PCa-speciic mortality while avoiding overtreatment by identifying of when to intervene, and in which patients.CONTENT: Currently, PCa prognosis and treatment decision of PCa involved digital rectal examination, Prostate-Speciic Antigens (PSA), and subsequent biopsies for histopathological staging, known as Gleason score. However, each procedure has its shortcomings. Efforts to find a better clinically meaningful and non-invasive biomarkers still developed involving proteins, circulating tumor cells, nucleic acids, and the ‘omics\u27 approaches.SUMMARY: Biomarkers for PCa will most likely be an assay employing multiple biomarkers in combination using protein and gene microarrays, containing markers that are differentially expressed in PCa

    Application of Umbilical Cord Blood Stem Cells in Regenerative Medicine

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    BACKGROUND: Since the first umbilical cord blood (UCB) transplant, performed 25 years ago, UCB banks have been established worldwide for the collection and cryopreservation of UCB for autologous and allogeneic transplants.CONTENT: Much has been learned in a relatively short time on the properties of UCB hematopoietic progenitors and their clinical application. More interestingly, non-hematopoietic stem cells have been isolated from UCB. These cells can be grown and differentiated into various tissues including bone, cartilage, liver, pancreas, nerve, muscle and so on. The non-hematopoietic stem cells have an advantage over other sources of stem cells, such as embryonic stem cells or induced pluripotent stem cells, because their supply is unlimited, they can be used in autologous or allogeneic situations, they need minimal manipulation and they raise no ethical concerns. Future studies will test the potential of UCB cells for the treatment of several diseases including, among other possibilities, diabetes, arthritis, burns, neurological disorder and myocardial infarction.SUMMARY: In addition to hematopoietic stem cells, UCB contain a large number of non-hematopoietic stem cells. In the absence of ethical concern, the unlimited supply of UCB cells explains the increasing interest of using UCB for developing regenerative medicine

    A Closer Look at Cardioprotective Function of HDL: Revise the HDL – Cholesterol Hypothesis?

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    BACKGROUND: The strong inverse association of plasma levels of high-density lipoprotein (HDL) cholesterol with coronary heart disease (CHD) found in human epidemiological studies led to the development of the ‘HDL cholesterol hypothesis', which posits that intervention to raise HDL cholesterol will result in reduced risk of CHD. A number of recent developments have brought the potential protective role of HDL into question. Several clinical trials of agents that substantially raise HDL-C have been demonstrated to not reduce CHD event rates.CONTENT: For decades, HDL and HDL-cholesterol (HDL-C) levels were viewed as synonymous, and modulation of HDL-C levels by drug therapy held great promise for the prevention and treatment of cardiovascular disease. Nevertheless, recent failures of drugs that raise HDL-C to reduce cardiovascular risk and the now greater understanding of the complexity of HDL composition and biology have prompted researchers in the field to redefine HDL. As such, the focus of HDL has now started to shift away from a cholesterol-centric view toward HDL particle number, subclasses, and other alternative metrics of HDL. Many of the recently discovered functions of HDL are, in fact, not strictly conferred by its ability to promote cholesterol flux but by the other molecules it transports, including a diverse set of proteins, small RNAs, hormones, carotenoids, vitamins, and bioactive lipids. Based on HDL's ability to interact with almost all cells and deliver fat-soluble cargo, HDL has the remarkable capacity to affect a wide variety of endocrine-like systems.SUMMARY: There is a significant need to redefine HDL and its benefit. HDL transports a diverse set of functional proteins, including many binding proteins. HDL transports and deliver vitamins, carotenoids, and other small molecules. Moreover, HDL transports hormones, steroids and bile acids, and can modulate multiple endocrine pathways. HDLs also transport and deliver microRNAs to recipient cells and control gene expression. Likewise, HDLs carry bioactive lipids and can activate signaling cascades and receptors that control endothelial apoptosis, migration, survival and activation. Many of HDL's alternative noncholesterol cargo likely confer many of HDL's alternative functions

    Macrophage Polarization in Metabolism and Metabolic Disease

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    BACKGROUND: Obesity is now recognized as the main cause of the worldwide epidemic of type 2 diabetes. Obesity-associated chronic inflammation is a contributing key factor for type 2 diabetes and cardiovascular disease. Numbers of studies have clearly demonstrated that the immune system and metabolism are highly integrated.CONTENT: Macrophages are an essential component of innate immunity and play a central role in inflammation and host defense. Moreover, these cells have homeostatic functions beyond defense, including tissue remodeling in ontogenesis and orchestration of metabolic functions. Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to interferons (IFNs), toll-like receptor (TLR), or interleukin (IL)-4/IL-13 signals, macrophages undergo M1 (classical) or M2 (alternative) activation. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1, M2 or M2-like polarized activation.SUMMARY: In response to various signals, macrophages may undergo classical M1 activation (stimulated by TLR ligands and IFN-γ) or alternative M2 activation (stimulated by IL-4/IL-13); these states mirror the T helper (Th)1–Th2 polarization of T cells. Pathology is frequently associated with dynamic changes in macrophage activation, with classically activated M1 cells implicate in initiating and sustaining inflammation, meanwhile M2 or M2-like activated cells associated with resolution or smoldering chronic inflammation. Identification of the mechanisms and molecules that are associated with macrophage plasticity and polarized activation provides a basis for macrophage centered diagnostic and therapeutic strategies

    Brown and Beige Fat: Therapeutic Potential in Obesity

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    BACKGROUND: The epidemic of obesity and type 2 diabetes presents a serious challenge to scientific and biomedical communities worldwide. There has been an upsurge of interest in the adipocyte coincident with the onset of the obesity epidemic and the realization that adipose tissue plays a major role in the regulation of metabolic function.CONTENT: Adipose tissue, best known for its role in fat storage, can also suppress weight gain and metabolic disease through the action of specialized, heat-producing adipocytes. Brown adipocytes are located in dedicated depots and express constitutively high levels of thermogenic genes, whereas inducible ‘brown-like' adipocytes, also known as beige cells, develop in white fat in response to various activators. The activities of brown and beige fat cells reduce metabolic disease, including obesity, in mice and correlate with leanness in humans. Many genes and pathways that regulate brown and beige adipocyte biology have now been identified, providing a variety of promising therapeutic targets for metabolic disease.SUMMARY: The complexity of adipose tissue presents numerous challenges but also several opportunities for therapeutic intervention. There is persuasive evidence from animal models that enhancement of the function of brown adipocytes, beige adipocytes or both in humans could be very effective for treating type 2 diabetes and obesity. Moreover, there are now an extensive variety of factors and pathways that could potentially be targeted for therapeutic effects. In particular, the discoveries of circulating factors, such as irisin, fibroblast growth factor (FGF)21 and natriuretic peptides, that enhance brown and beige fat function in mice have garnered tremendous interest. Certainly, the next decade will see massive efforts to use beige and brown fat to ameliorate human metabolic disease

    MicroRNAs in Lipid Metabolism and Atherosclerosis

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    BACKGROUND: MicroRNAs (miRNA) are mediators of post-transcriptional gene expression that likely regulate most biological pathways and networks. The study of miRNAs is a rapidly emerging field; recent findings have revealed a significant role for miRNAs in atherosclerosis and lipoprotein metabolism.CONTENT: Results from recent studies demonstrated a role for miRNAs in endothelial integrity, macrophage inflammatory response to oxidized low-density lipoprotein, vascular smooth muscle cell proliferation and cholesterol synthesis. These mechanisms are all vital to the initiation and proliferation of atherosclerosis and cardiovascular disease. The importance of miRNAs has recently been recognized in cardiovascular sciences and miRNAs will likely become an integral part of our fundamental comprehension of atherosclerosis and lipoprotein metabolism. The extensive impact of miRNA mediated gene regulation and the relative ease of in vivo applicable modifications highlight the enormous potential of miRNA-based therapeutics in cardiovascular diseases.SUMMARY: miRNA studies in the field of lipid metabolism and atherosclerosis are in their infancy, and thus there is tremendous opportunity for discovery in this understudied area. The ability to target miRNAs in vivo through delivery of miRNA-mimics to enhance miRNA function, or antimiRNAs which inhibit miRNAs, has opened new avenues for the development of therapeutics for dyslipidemias and atherosclerosis, offers a unique approach to treating disease by modulating entire biological pathways. These exciting findings support the development of miRNA antagonists as potential therapeutics for the treatment of dyslipidaemia, atherosclerosis and related metabolic diseases

    Telomere in Aging and Age-Related Diseases

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    BACKGROUND: The number of elderly population in the world keep increasing. In their advanced ages, many elderly face years of disability because of multiple chronic diseases, frailty, making them lost their independence. Consequently, this could have impacts on social and economic stability. A huge challenge has been sent for biomedical researchers to compress or at least eliminate this period of disability and increase the health span.CONTENT: Over the past decades, many studies of telomere biology have demonstrated that telomeres and telomere-associated proteins are implicated in human diseases. Accelerated telomere erosion was clearly correlated with a pack of metabolic and inflammatory diseases. Critically short telomeres or the unprotected end, are likely to form telomeric fusion, generating genomic instability, the cornerstone for carcinogenesis. Enlightening how telomeres involved in the mechanisms underlying the diseases' pathogenesis was expected to uncover new molecular targets for any important diagnosis or therapeutic implications.SUMMARY: Telomere shortening was foreseen as an imporant mechanism to supress tumor by limiting cellular proliferative capacity by regulating senescence check point activation. Many human diseases and carcinogenesis are causally related to defective telomeres, asserting the importance of telomeres sustainment. Thus, telomere length assessment might serve as an important tool for clinical prognostic, diagnostic, monitoring and management

    Adipose Tissue, Inflammation (Meta-inflammation) and Obesity Management

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    BACKGROUND: Obesity-induced inflammation contributes to the development of type 2 diabetes, metabolic syndrome, and cardiovascular disease.CONTENT:The last decade has seen a sharp increase in our appreciation for the macrophage as a critical regulator of metabolic status in obesity. Activation of adipose tissue (AT) macrophages within fat depots is coupled with the development of obesity-induced proinflammatory state and insulin resistance (IR). The activation of classically activated M1 macrophages at the expense of anti-inflammatory M2 macrophages has been causally linked to the development of AT inflammation and metabolic syndrome, a pathophysiological state aptly termed as ‘metainflammation'. It is recognized that several proinflammatory cytokines, including interleukin (IL)-1β, are implicated in disrupting insulin signaling. Our developing appreciation of links among obesity, inflammation and cardiovascular disease will require multiple complementary approaches to leverage new concepts into translatable outcomes. Careful characterization of human patients, particularly analysis of AT distribution, will be needed to stratify subjects that are most likely obese/metabolically healthy from those that are obese/metabolically unhealthy.SUMMARY: It has been suggested that individuals with the condition known as metabolically healthy obese (MHO) may not have the same increased risk for the development of metabolic abnormalities as their non-metabolically healthy counterparts. A complications-centric model for the medical management of obesity emphasizes the identification and staging of complications, and treatment paradigm directed at patients who would gain the most benefit from weight loss
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