Serum levels of interleukin-33, soluble ST2 and IgE in patients with asthma: a case-control study.

INTRODUCTION: Interleukins play a very important role in the pathophysiology of asthma. Interleukin-33 (IL-33) is a partially explored cytokine in asthma. It binds with a specific receptor called suppression of tumorigenicity 2 (ST2). The study aims to evaluate the serum levels of IL-33, sST2 and IgE in asthmatic patients and healthy controls and its further association with the forced expiratory volume in one second (FEV 1%) and absolute eosinophil count. MATERIALS AND METHODS: We enrolled 100 asthmatic patients and 57 healthy subjects for the study. We measured serum levels of IgE, IL-33, and sST2. Based on serum IgE levels, patients were divided into allergic and non-allergic groups. Statistical analysis was done by using Graph pad prism software 8. RESULTS: We found significantly elevated levels of IL-33 and IgE in asthmatic patients as compared to healthy subjects. However, sST2 levels were significantly lower in asthmatic patients than in healthy subjects. FEV1% values were decreased in uncontrolled asthmatic patients. In addition, serum levels of IL-33 were significantly correlated with the IgE. Furthermore, we found a significant correlation between IL-33 and AEC in allergic asthmatic patients. CONCLUSION: In this study, we reported elevated IL-33 and IgE levels and decreased sST2 levels in asthmatic patients compared to healthy controls. IL-33 and sST2 may act as inflammatory biomarkers for allergic diseases such as asthma.

Evaluation of interleukin-33 & sST2 levels in type-2 diabetic mellitus patients with or without metabolic syndrome.

Background & objectives: Diabetes mellitus (DM) is characterized by increase in blood glucose levels due to defective insulin secretion or insulin sensitivity. Interleukins (ILs) are known to play an important role in the pathogenesis of DM. The aim of this study was to investigate the serum concentration of IL-33 and its receptor soluble ST2 (sST2) in patients with diabetes and draw a correlation between their serum levels and different standard glycaemic indices of patients affected with type-2 diabetes with or without metabolic syndrome. Methods: Thirty type-2 diabetic individuals and 30 healthy controls were recruited for this study. Serum and plasma were separated by centrifugation of blood for quantitative measurement of IL-33, sST2 and other biochemical parameters. Results: It was observed that serum IL-33 levels were significantly less and sST2 levels were significantly high in type-2 diabetic individuals as compared to healthy controls. A significant correlation between the serum IL-33 concentration and fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels were also found. Additionally, data also elucidated that serum levels of high-density lipoprotein, low-density lipoprotein or triglyceride in type-2 diabetics did not influence the serum levels of IL-33 and sST2, thereby excluding these factors as the major drivers of changes in serum IL-33 and sST2 concentration. Interpretation & conclusions: This study demonstrated alteration in serum levels of IL-33 and sST2 in type-2 diabetic individuals. Further mechanistic studies, focusing on the progression of type-2 diabetes could elucidate the involvement of IL-33 in the cellular acquisition of insulin resistance as observed in type-2 diabetics.

Safety and Performance of Continuous Glucose Monitoring: An Overview.

Diabetes (Type 1 and Type 2) is the most burdensome condition for the healthcare systems worldwide. Continuous glucose monitoring (CGM) is a powerful tool in the management of diabetes that has helped patients with diabetes to achieve better glycemic control as compared to traditional systems. It helps reduce the frequency as well as the severity of hypoglycemia. Continuous glucose monitoring technology is an integral part of the 'artificial pancreas'. This review provides an overview of CGM technology and its applications.

Evaluation of serum interleukin-33 and soluble suppression of tumorigenicity 2 (sST2) receptors in patients with and without periodontal disease.

Context: : Interleukin-33 and its receptor soluble suppression of tumorigenicity 2. (: sST2) play an important role in inflammation and its role in periodontal disease is yet unclear. The role of both IL-33 and sST2 together in periodontal disease as biomarkers has never been studied. Aim: : To assess the levels of IL-33 and sST2 in serum samples of patients with periodontitis and healthy subjects. Methods: : A total of 71 subjects (30 healthy subjects and 41 patients with periodontal disease) were included in the cross-sectional study. Community Periodontal Index (CPI) was used to assess periodontal health by utilizing a mouth mirror and a CPI probe. Venous blood was collected and serum was separated. Serum levels of IL-33 and sST2 were determined by the enzyme-linked immunosorbent assay (ELISA) assay. Statistical Analysis: Graph Pad Prism 5 was used for statistical analysis. Mann Whitney test was applied to compare the two groups. Results: : The level of IL-33 was not found to be elevated among healthy subjects and sST2 was found elevated among patients with periodontal disease. The serum concentration of IL-33 was found at 472 ± 114 pg/ml and 282 ± 77 pg/ml among healthy subjects and patients with periodontal disease respectively. Significantly higher values of sST2 at 28 ± 2 ng/ml were found among periodontal patients as compared to healthy subjects with values of 18 ± 1 ng/ml. No significant differences were noted between mild to moderate and severe periodontitis for IL-33 and sST2 between the two groups. Conclusion: This study shows alteration in serum levels of IL-33 and sST2 in periodontitis patients. IL-33 and sST2 may be potential inflammatory markers of periodontitis. Further studies are required on a large sample size for better understanding. This pilot study is the first to assess the serum levels of both IL-33 and sST2 together among patients with and without periodontal disease.

The Interplay of Oxidative Stress and ROS Scavenging: Antioxidants as a Therapeutic Potential in Sepsis.

Oxidative stress resulting from the disproportion of oxidants and antioxidants contributes to both physiological and pathological conditions in sepsis. To combat this, the antioxidant defense system comes into the picture, which contributes to limiting the amount of reactive oxygen species (ROS) leading to the reduction of oxidative stress. However, a strong relationship has been found between scavengers of ROS and antioxidants in preclinical in vitro and in vivo models. ROS is widely believed to cause human pathology most specifically in sepsis, where a small increase in ROS levels activates signaling pathways to initiate biological processes. An inclusive understanding of the effects of ROS scavenging in cellular antioxidant signaling is essentially lacking in sepsis. This review compiles the mechanisms of ROS scavenging as well as oxidative damage in sepsis, as well as antioxidants as a potent therapeutic. Direct interaction between ROS and cellular pathways greatly affects sepsis, but such interaction does not provide the explanation behind diverse biological outcomes. Animal models of sepsis and a number of clinical trials with septic patients exploring the efficiency of antioxidants in sepsis are reviewed. In line with this, both enzymatic and non-enzymatic antioxidants were effective, and results from recent studies are promising. The usage of these potent antioxidants in sepsis patients would greatly impact the field of medicine.

Emerging Therapeutic Targets for Metabolic Syndrome: Lessons from Animal Models.

BACKGROUND: Metabolic syndrome is a cluster of medical conditions that synergistically increase the risk of heart diseases and diabetes. The current treatment strategy for metabolic syndrome focuses on treating its individual components. A highly effective agent for metabolic syndrome has yet to be developed. To develop a target for metabolic syndrome, the mechanism encompassing different organs - nervous system, pancreas, skeletal muscle, liver and adipose tissue - needs to be understood. Many animal models have been developed to understand the pathophysiology of metabolic syndrome. Promising molecular targets have emerged while characterizing these animals. Modulating these targets is expected to treat some components of metabolic syndrome. OBJECTIVE: To discuss the emerging molecular targets in an animal model of metabolic syndrome. METHODS: A literature search was performed for the retrieval of relevant articles. CONCLUSION: Multiple genes/pathways that play important role in the development of Metabolic Syndrome are discussed.

Treatment of 'Diabesity': Beyond Pharmacotherapy.

Obesity is a prominent risk factor for type 2 diabetes. Management of type 2 diabetes requires weight management in addition to glycemic parameters. For obese type 2 diabetes patients, metformin, Sodium-glucose co-transporter-2 inhibitors or Glucagon-Like Peptide-1 Receptor Agonists should be prescribed as the first priority for controlling both hyperglycemia and body weight or fat distribution. The combination of these drugs with sulfonylureas, thiazolidinediones, and insulin may also be required in chronic cases. These drugs cause weight gain. Fortunately, many phytochemicals having a beneficial effect on diabetes and obesity, have minimum side-effects as compared to synthetic drugs. This review discusses the treatment strategies for controlling glycemia and weight management, with the focus on anti-diabetic drugs and phytochemicals. Glucagonostatic role, activation of Adenosine monophosphate-activated protein kinase and adipocyte targeting potential of anti-diabetic drugs and phytochemicals are also discussed.

The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation: The Hunt for New Therapeutic Targets.

Histamine and its receptors (H1R-H4R) play a crucial and significant role in the development of various allergic diseases. Mast cells are multifunctional bone marrow-derived tissue-dwelling cells that are the major producer of histamine in the body. H1R are expressed in many cells, including mast cells, and are involved in Type 1 hypersensitivity reactions. H2R are involved in Th1 lymphocyte cytokine production. H3R are mainly involved in blood-brain barrier function. H4R are highly expressed on mast cells where their stimulation exacerbates histamine and cytokine generation. Both H1R and H4R have important roles in the progression and modulation of histamine-mediated allergic diseases. Antihistamines that target H1R alone are not entirely effective in the treatment of acute pruritus, atopic dermatitis, allergic asthma, and other allergic diseases. However, antagonists that target H4R have shown promising effects in preclinical and clinical studies in the treatment of several allergic diseases. In the present review, we examine the accumulating evidence suggesting novel therapeutic approaches that explore both H1R and H4R as therapeutic targets for histamine-mediated allergic diseases.

Islet Compensation in Metabolic Stress: Lessons from Animal Models.

Type 2 diabetes is characterized by decreased functional beta-cell mass, as a consequence of metabolic stress associated with obesity, aging, insulin resistance and pregnancy. The metabolic stress is caused by increased insulin demand, pro-inflammatory cytokines, and free fatty acids. Fortunately, islets have remarkable property to adapt to increased metabolic demand. This review focuses on the mechanisms of islet adaptation to metabolic stress in obesity and insulin resistance.

Beta-cell Management in Type 2 Diabetes: Beneficial Role of Nutraceuticals.

Inadequate functional beta cell mass seems to be the primary cause of type 2 diabetes. Increased oxidative stress and inflammation are the leading causes of betacell death. Preservation of functional beta-cell mass in type 2 diabetes is a critical target for type 2 diabetes management. Numerous studies have demonstrated beneficial effects of dietary components on beta cell management in type 2 diabetes, through multiple mechanisms. These dietary components modulate intercellular cascades that inhibit inflammatory molecule synthesis, the formation of free radicals, and nuclear damage, as well as induce antioxidant enzyme expression. The present review article focuses on dietary components and seeks to summarize their mechanism(s) in the prevention of diabetes initiation and progression through beta-cell management in type 2 diabetes.

Progenitor cells may aid successful islet compensation in metabolically healthy obese individuals.

Obesity is associated with insulin resistance and type 2 diabetes. Fortunately most obese, insulin-resistant individuals do not develop type 2 diabetes as they can overcome reduced efficiency of insulin action by increasing the functional ß-cell mass. Compelling evidences suggest ß-cells neogenesis through progenitor/stem cells residing in pancreatic ductal cells and islets, but the role of ß-cell regeneration in obesity/insulin resistance from progenitor/stem cells is not clear. Based on many indirect evidences in human studies such as unchanged ß-cell replication, apoptosis and size during compensation in insulin resistance in humans, we suggest successful ß-cells mass compensation in metabolically healthy obesity is contributed by neoformation of ß-cells, through expansion of progenitor cells/stem cells in synergy with ß-cell replication.

Islet adaptation to obesity and insulin resistance in WNIN/GR-Ob rats.

WNIN/GR-Ob mutant rat is a novel animal model to study metabolic syndrome (obesity, insulin resistance, hyperinsulinemia, impaired glucose tolerance and cardiovascular diseases). We have investigated the islet characteristics of obese mutants at different age groups (1, 6 and 12 months) to assess the islet changes in response to early and chronic metabolic stress. Our data demonstrates altered islet cell morphology and function (hypertrophy, fibrotic lesions, vacuolation, decreased stimulation index, increased TNFα, ROS and TBARS levels) in mutants as compared to controls. Furthermore, network analysis (gene-gene interaction) studied in pancreas demonstrated increased inflammation as a key factor underlying obesity/metabolic syndrome in mutants. These observations pave way to explore this model to understand islet adaptation in response to metabolic syndrome.

Novel genes underlying beta cell survival in metabolic stress.

Relative insulin deficiency, in response to increased metabolic demand (obesity, genetic insulin resistance, pregnancy and aging) lead to Type2 diabetes. Susceptibility of the type 2 diabetes has a genetic basis, as a subset of people with risk factors (obesity, Insulin Resistance, pregnancy), develop Type2 Diabetes. We aimed to identify 'cluster' of overexpressed genes, underlying increased beta cell survival in diabetes resistant C57BL/6J ob/ob mice (compared to diabetes susceptible BTBR ob/ob mice). We used 'consensus' overexpression status to identify 'cluster' of 11 genes consisting of Aldh18a1, Rfc4, Dynlt3, Prom1, H13, Psen1, Ssr4, Dad1, Anpep, Fam111a and Plk1. Information (biological processes, molecular functions, cellular components, protein-protein interactions/associations, gene deletion/knockout/inhibition studies) of all the genes in 'cluster' were collected by text mining using different literature search tools, gene information databases and protein-protein interaction databases. Beta cell specific function of these genes were also inferred using meta analysis tool of Beta Cell Biology Consortium, by studying the expression pattern of these genes in microarray studies related to beta-cell stimulation/injury, pancreas development and growth and cell differentiation. In the 'clusters', 6 genes (Dad1, Psen1, Ssr4, Rfc4, H13, Plk1) have a role in cell survival. Only Psen1 was previously identified to have role in successful beta cell compensation. We advocate these genes to be potentially involved in successful beta cell compensation and prevent T2D in humans, by conferring protection against diabetogenic insults.

Deriving at candidate genes of metabolic stress from pancreas of WNIN/GR-Ob mutant rats.

Development of appropriate animal model systems have greatly helped our understanding of the basic mechanism(s) of several degenerative diseases. WNIN/GR-Ob?a mutant rat strain developed at the National Center for Laboratory Animal Sciences facility of National Institute of Nutrition, is a new animal model ideal to study the metabolic syndrome since it is obese with impaired glucose tolerance and also exhibits several secondary complications. The present study was performed in the pancreas of this mutant model to assess the global gene expression (microarray) to assess the transcriptome level changes in situ depicting inflammation, obesity, insulin resistance, and diabetes in these animals. Our findings suggest an interplay of several confounding factors in pancreas which include inflammation /macrophage infiltration/apoptosis/oxidative and endoplasmic reticulum stress, all contributing for the shift toward pro-inflammation. We were able to phenotypically correlate the metabolic alterations vis-a-vis candidate genes (array analyses) compared between mutants and its age matched, parental controls. We advocate that the data reported here would provide a suitable insight in to the pathophysiology of metabolic syndrome .

Pyridoxal 5' phosphate protects islets against streptozotocin-induced beta-cell dysfunction--in vitro and in vivo.

Administration of pyridoxal 5' phosphate (PLP) has demonstrated beneficial effects in the management of diabetes, albeit the mechanism(s) are not clearly understood. The present study addressed the islet-cell function(s) in streptozotocin (STZ)-induced diabetic mice both in vitro and in vivo. Primary islet cells primed with or without PLP (5 mmol/L) were treated with STZ (2 mmol/L) and were measured for cell viability, insulin secretion, free radicals and mRNA of Insulin and Pdx1. The specificity of PLP's response on insulin secretion was assessed with amino oxy acetic acid (AOAA)-PLP inhibitor. In vivo, the STZ (200 mg/kg b.w)-treated diabetic mice received 10 mmol/L PLP intraperitoneally a day before (PLP + STZ) or after (STZ + PLP) with three more doses once every 48 h. On 7, 14 and 21 d of STZ treatment, physiological parameters, islet morphology, insulin:glucagon, insulin:HSP104, and mRNA of Insulin, Glut2, Pdx1 and Reg1 were determined. In vitro, PLP protected islets against STZ-induced changes in viability, insulin secretion, prevented increase in free radical levels and normalized mRNA of Insulin and Pdx1. Further, AOAA inhibited PLP-induced insulin secretion in islets. In vivo, PLP treatment normalized STZ-induced changes in physiological parameters, circulating levels of PLP and insulin. Also, islet morphology, insulin:glucagon, insulin:HSP104 and mRNA levels of Insulin, Pdx1 and Glut2 were restored by 21 d. Although PLP treatment (pre- and post-STZ) prevented development of frank diabetes, STZ + PLP mice showed transient hyperglycemia, and increased mRNA for Reg1. The data suggest the cytoprotective vis-à-vis insulinotrophic effects of PLP against STZ-induced beta-cell dysfunction and underline its prophylactic use in the management of diabetes.