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Endocrine System Diseases - Top 30 Publications

IL-36α suppresses proliferation of ovarian cancer cells.

Interleukin-36α (IL-36α), also formerly known as IL-1F6, is pertaining to IL-1 family members that has been shown to play an important pro-inflammatory role in chronic immune disorders. However, the role IL-36α in the setting of cancer remains unknown. Here, in our study, to investigate the clinical relevance of IL-36α in ovarian cancer, clinicopathological significance as well as expression level of IL-36α were analyzed in epithelial ovarian cancer clinical tissues and paired normal control. To explore the biological role of IL-36α in vitro in epithelial ovarian cancer cells, both overexpression and knockdown of IL-36α were performed. Based on the successful re-expression and silencing of IL-36α, proliferation, migration, and invasion were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound-healing, and Transwell assays, respectively. To further confirm the effect over proliferation in vivo, nude mice xenografted with epithelial ovarian cancer cells whose endogenous IL-36α was stably upregulated or downregulated were employed. It was found that IL-36α was shown to be markedly downregulated in epithelial ovarian cancer tissues relative to paired normal control and that reduced IL-36α expression was significantly associated with poor overall prognosis. In addition, IL-36α was observed to be able to suppress the growth of epithelial ovarian cancer cells both in vivo and in vitro. Taken together, IL-36α was displayed to be able to suppress the growth of epithelial ovarian cancer cells in our setting, which is suggestive of its druggable potential in curing the epithelial ovarian cancer and that upregulation of IL-36α was found to be capable of inhibiting the growth of epithelial ovarian cancer cells.

Pilot randomized controlled trial of a mindfulness-based group intervention in adolescent girls at risk for type 2 diabetes with depressive symptoms.

(1) Evaluate feasibility and acceptability of a mindfulness-based group in adolescent girls at-risk for type 2 diabetes (T2D) with depressive symptoms, and (2) compare efficacy of a mindfulness-based versus cognitive-behavioral group for decreasing depressive symptoms and improving insulin resistance.

Impact of mulberry leaf extract on type 2 diabetes (Mul-DM): A randomized, placebo-controlled pilot study.

Mulberry leaves have been used anecdotally in Asia to treat many disease states, including glucose abnormalities. Animal and human studies illustrate potential benefit of mulberry leaf extract (MLE) in type 2 diabetes mellitus (DM2). The purpose of this study is to evaluate the glycemic and safety effects of MLE in patients with DM2.

Announcement: Community Preventive Services Task Force Recommendation for Team-Based Care for Patients with Type 2 Diabetes.

The Community Preventive Services Task Force recently posted new information on its website: "Diabetes Management: Team-Based Care for Patients with Type 2 Diabetes." The information is available at

Prevalence of Autoantibodies against 3-DG-Glycated H2A Protein in Type 2 Diabetes.

Advanced glycation end-products (AGEs) have been found to be critically involved in initiation or progression of diabetes secondary complications (nephropathy, retinopathy, neuropathy, and angiopathy). Various hyper-glycating carbonyl compounds such as 3-deoxyglucosone (3-DG) are produced in pathophysiological conditions that form AGEs in high quantity both in vivo and in vitro. In the first stage of this study, we glycated histone H2A protein by 3-DG, and the results showed the formation of various intermediates and AGEs as well as structural changes in the protein. In the second stage, we studied the immunogenicity of native and 3-DG-glycated H2A protein in female rabbits. The modified H2A was highly immunogenic, eliciting high titer immunogen-specific antibodies, while the unmodified form was almost nonimmunogenic. Antibodies against standard carboxymethyllysine (CML) and pentosidine were detected in the immunized female rabbits, which demonstrates the immunogenic nature of AGEs (CML and pentosidine) as well. The results show both structural perturbation and AGEs have the capacity of triggering the immune system due to the generation of neoepitopes that render the molecule immunogenic. This study shows the presence of autoantibodies against 3-DG-modified H2A, CML, and pentosidine in the sera of type 2 diabetes patients having secondary complications. Autoantibodies against damaged H2A and AGEs may be significant in the assessment of initiation/progression of secondary complications in type 2 diabetes mellitus patients or may be used as a marker for early detection of secondary complications in diabetes.

Molecular Mechanisms of Ovarian Carcinoma Metastasis: Key Genes and Regulatory MicroRNAs.

Metastasis of primary tumors progresses stepwise - from change in biochemistry, morphology, and migratory patterns of tumor cells to the emergence of receptors on their surface that facilitate directional migration to target organs followed by the formation of a specific microenvironment in a target organ that helps attachment and survival of metastatic cells. A set of specific genes and signaling pathways mediate this process under control of microRNA. The molecular mechanisms underlying biological processes associated with tumor metastasis are reviewed in this publication using ovarian cancer, which exhibits high metastatic potential, as an example. Information and data on the genes and regulatory microRNAs involved in the formation of cancer stem cells, epithelial-mesenchymal transition, reducing focal adhesion, degradation of extracellular matrix, increasing migration activity of cancer cells, formation of spheroids, apoptosis, autophagy, angiogenesis, formation of metastases, and development of ascites are presented. Clusters of microRNAs (miR-145, miR-31, miR-506, miR-101) most essential for metastasis of ovarian cancer including the families of microRNAs (miR-200, miR-214, miR-25) with dual role, which is different in different histological types of ovarian cancer, are discussed in detail in a section of the review.

Incretin based treatments and mortality in patients with type 2 diabetes: systematic review and meta-analysis.

Objective To assess the impact of incretin based treatment on all cause mortality in patients with type 2 diabetes.Design Systematic review and meta-analysis of randomised trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and criteria Randomised controlled trials that compared glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors with placebo or active anti-diabetic drugs in patients with type 2 diabetes.Data collection and analysis Paired reviewers independently screened citations, assessed risk of bias of included studies, and extracted data. Peto's method was used as the primary approach to pool effect estimates from trials, sensitivity analyses were carried out with other statistical approaches, and meta-regression was applied for six prespecified hypotheses to explore heterogeneity. The GRADE approach was used to rate the quality of evidence.Results 189 randomised controlled trials (n=155 145) were included, all of which were at low to moderate risk of bias; 77 reported no events of death and 112 reported 3888 deaths among 151 614 patients. Meta-analysis of 189 trials showed no difference in all cause mortality between incretin drugs versus control (1925/84 136 v 1963/67 478; odds ratio 0.96, 95% confidence interval 0.90 to 1.02, I(2)=0%; risk difference 3 fewer events (95% confidence interval 7 fewer to 1 more) per 1000 patients over five years; moderate quality evidence). Results suggested the possibility of a mortality benefit with GLP-1 agonists but not DPP-4 inhibitors, but the subgroup hypothesis had low credibility. Sensitivity analyses showed no important differences in the estimates of effects.Conclusions Current evidence does not support the suggestion that incretin based treatment increases all cause mortality in patients with type 2 diabetes. Further studies are warranted to examine if the effect differs between GLP-1 agonists versus DPP-4 inhibitors.

Risk of Diabetic Ketoacidosis after Initiation of an SGLT2 Inhibitor.

Dietary Intake of Omega-3 Fatty Acids From Fish and Risk of Diabetic Retinopathy.

Body mass index and risk of diabetic retinopathy: A meta-analysis and systematic review.

Diabetic retinopathy (DR) is a frequent cause of acquired blindness worldwide. Various studies have reported the effects of body mass index (BMI) on the risk of DR, but the results remain controversial. Therefore, a meta-analysis was performed to evaluate the relationship between BMI and the risk of DR.A systematic search was performed using the Cochrane Library, PubMed, and Embase databases to obtain articles published through December 2016. Articles regarding the association between BMI and the risk of DR were retrieved. The adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were included and then pooled with a random effects model.A total of 27 articles were included in this meta-analysis. When BMI was analyzed as a categorical variable, neither being overweight (OR = 0.89, 95% CI 0.75-1.07; P = .21; I = 65%) nor obesity (OR = 0.97, 95% CI 0.73-1.30; P = .86) were associated with an increased risk of DR when compared with normal weight. When BMI was analyzed as a continuous variable, a higher BMI was not associated with an increased risk of DR (OR = 0.99, 95% CI 0.97-1.01; P = .25; I2 = 79%). The pooled results did not significantly change after the sensitivity analysis.Based on the current publications, neither being overweight nor obesity is associated with an increased risk of DR. Further studies should confirm these findings.

MicroRNA-141-3p targets DAPK1 and inhibits apoptosis in rat ovarian granulosa cells.

The polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disorder. MicroRNAs negatively regulate the expression of target genes at posttranscriptional level by binding to the 3' untranslated region of target genes. Our previous study showed that miR-141-3p was dramatically decreased in the ovaries of rat PCOS models. In this study, we aimed to characterize the target of miR-141-3p in rat ovarian granulosa cells. 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay showed that cell viability was dramatically increased when miR-141-3p was overexpressed but was decreased when miR-141-3p was interfered. Flow cytometry showed that cell apoptotic rate was dramatically decreased when miR-141-3p was overexpressed but was increased when miR-141-3p was interfered. Bioinformatics analysis predicted that death-associated protein kinase 1 (DAPK1) might be the target gene of miR-141-3p because the 3' untranslated region of DAPK1 contains sequences complementary to microRNA-141-3p. Transfection with miR-141-3p mimics and inhibitor into granulosa cells showed that both DAPK1 mRNA and protein levels were negatively correlated with miR-141-3p level. Dual-luciferase reporter assay established that DAPK1 was the target of miR-141-3p. Taken together, our data indicate that miR-141-3p may inhibit ovarian granulosa cell apoptosis via targeting DAPK1 and is involved in the etiology of PCOS.

Metabolic Effect of 1-Deoxynojirimycin from Mulberry Leaves on db/db Diabetic Mice Using Liquid Chromatography-Mass Spectrometry Based Metabolomics.

Metabolomics was applied to the liquid chromatography-mass spectrometry urinary metabolic profile of type 2 diabetes (T2DM) mice treated with mulberry 1-deoxynojirimycin (DNJ). The serum biochemical indicators related to T2DM like blood glucose, insulin, triglyceride, total cholesterol, nitrogen, malondialdehyde, and creatinine decreased significantly in the treated group. The histopathological changes in liver cells were marked by deformations and disruptions in central area of nuclei in DM mice, whereas DNJ treatment recovered regular liver cells with normal nuclei. Most of the metabolites of T2DM were significantly different from healthy controls in the bulk data generated. The level of 16 metabolites showed that the diabetic group was closer to the healthy group as the DNJ treatment time prolonged. Moreover, DNJ inhibited the activity of glucosidase on glucose, lipid, and amino acid metabolism. Our results showed the mechanism of DNJ treatment of T2DM and could fetch deep insights into the potent metabolite markers of the applied antidiabetic interventions.

Prognostic factors for tumor recurrence in endometrioid endometrial cancer stages IA and IB.

Risk grouping for treatment and follow-up strategy of early stage endometrial cancer is confusing to apply in clinical conditions. We investigated the stage-based prognostic factors for tumor recurrence in stage I endometrial cancer with endometrioid histology (EEC).The medical records of women diagnosed with endometrial adenocarcinoma between 1993 and 2013 were retrospectively reviewed. In 521 patients with International Federation of Gynecology and Obstetrics (FIGO) stage I EEC were included. The baseline patient characteristics were analyzed with the chi-square test and Fisher's exact tests. A multivariate analysis with a Cox proportional hazard model and logistic regression were performed to identify the prognostic factors for recurrence-free survival (RFS) in FIGO stage I EEC.The median follow-up period for the included patients was 74.6 months (3.1-264.9 months). Tumor recurrence occurred in 30 patients (5.8%) with a median time span of 22.85 months (2.2-124.7 months). Only 2 factors among the conventional adverse risk factors, including myometrial invasion and histologic grade, affected tumor recurrence in stage I EEC (P = .003 and P = .003, respectively). Myometrial invasion was an independent prognostic factor for RFS in stage IA EEC via multivariate analysis (P = .005). In stage IB EEC, the histologic grade was an independent prognostic factor for RFS. The median RFS of stage IB EEC was 156.0 months in grade 1, 120.0 months in grade 2, and 105.9 months in grade 3 (P = .006).Within stage I EEC, the prognostic factors for tumor recurrence were different between stages IA and IB. Myometrial invasion comprised the prognostic factor in stage IA, whereas the histologic grade comprised the prognostic factor in stage IB.

The effect of alpha-linolenic acid on glycemic control in individuals with type 2 diabetes: A systematic review and meta-analysis of randomized controlled clinical trials.

Polyunsaturated fats (PUFAs) have been shown to reduce type 2 diabetes (T2DM) risk and improve insulin responsiveness in T2DM subjects, but whether the plant sources of omega-3 PUFA (alpha-linolenic acid [ALA]) have an effect on glycemic control requires further investigation.

Relation of total sugars, fructose and sucrose with incident type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies.

Sugar-sweetened beverages are associated with type 2 diabetes. To assess whether this association holds for the fructose-containing sugars they contain, we conducted a systematic review and meta-analysis of prospective cohort studies.

Dosing of Etelcalcetide vs Cinacalcet for Secondary Hyperparathyroidism-Reply.

Dosing of Etelcalcetide and Cinacalcet for Secondary Hyperparathyroidism.

Primary leiomyosarcoma of thyroid gland: the youngest case.

Primary leiomyosarcomas of the thyroid gland are extremely rare. We report a case of a 32 year-old women with a multinodular goiter. She underwent total thyroidectomy. The tumor histology showed spindle-shaped cells that expressed desmine, caldesmone and smooth muscle actine but were negative cytokeratins.

Disparities in Diabetes Deaths Among Children and Adolescents - United States, 2000-2014.

Diabetes is a common chronic disease of childhood affecting approximately 200,000 children and adolescents in the United States (1). Children and adolescents with diabetes are at increased risk for death from acute complications of diabetes, including hypoglycemia and diabetic ketoacidosis (2,3); in 2012, CDC reported that during 1968-2009, diabetes mortality among U.S. persons aged ≤19 years declined by 61% (4). CDC observed disparities by race during 1979-2004, with black children and adolescents dying from diabetes at twice the rate of white children and adolescents (5). However, no previous study has examined Hispanic ethnicity. CDC analyzed data from the National Vital Statistics System for deaths among persons aged 1-19 years in the United States during 2000-2014, with diabetes listed as the underlying cause of death overall, and for Hispanic, non-Hispanic white (white), and non-Hispanic black (black) children and adolescents. During 2012-2014, black children and adolescents had the highest diabetes death rate (2.04 per 1 million population), followed by whites (0.92) and Hispanics (0.61). There were no statistically significant changes in diabetes death rates over the study period, but disparities persisted among racial/ethnic groups. Death from diabetes in children and adolescents is potentially preventable through increased awareness of diabetes symptoms (including symptoms of low blood sugar), earlier treatment and education related to diabetes, and management of diabetes ketoacidosis. Continued measures are needed to reduce diabetes mortality in children and understand the cause of racial and ethnic disparities.

Bariatric Surgery or Intensive Medical Therapy for Diabetes after 5 Years.

Effect of omega-3 supplementation on neuropathy in type 1 diabetes: A 12-month pilot trial.

To test the hypothesis that 12 months of seal oil omega-3 polyunsaturated fatty acids (ω-3 PUFA) supplementation will stop the known progression of diabetic sensorimotor polyneuropathy (DSP) in type 1 diabetes mellitus (T1DM).

Cardiovascular Effects of Antidiabetic Therapies.

Type 2- diabetes mellitus (T2DM) represents a major risk factor for cardiovascular complications and mortality. Strict glucose control in the early course of the disease prevents cardiovascular complications only in the long run. Non-medical therapies (diet, exercise, body weight reduction) bear little evidence for positive cardiovascular effects.Bariatric surgery is not number one choice in therapy of T2DM. Metformin seems to provide positive cardiovascular effects. Insulin seems to be cardiovascular neutral, as well as the DPP4-inhibitors Saxagliptin, Sitagliptin and Alogliptin. Concerning GLP-1-RAs, Lixisenatide has a neutral cardiovascular effect, whereas Liraglutide and Semaglutide reduce cardiovascular outcomes. The SGLT2-inhibitor Empagliflozin reduces cardiovascular mortality, total mortality and hospitalization by heart failure.

The Way to Closed Loop - Dream and Reality.

An old dream of patients with type 1 diabetes and medical teams alike is a fully automated insulin therapy. Available sensor-augmented insulin-pumps are able to intervene in insulin therapy by reducing the dose. Aim of several studies is to add an algorithm to the interaction of pump and sensor, so that insulin doses can be regulated fully automatically. Totally closed loop systems are currently not yet available for outpatient use. Hybrid closed loop systems have been approved in the US. They can improve the metabolic status of patients with type 1 diabetes. Risks are similar to sensor-augmented insulin-pump therapy. Patients' detailed education will continue to be essential for success.

Diagnostic Approach to Manifestation of Type 1 Diabetes mellitus.

The incidence of type 1 and type 2 diabetes mellitus has been increasing simultaneously. Formerly, these two patients' populations could be differentiated easily, but now, due to the overlapping of both groups, specified diagnostics are necessary. In order to substantiate a suspicion on diabetes, quantifying venous plasma glucose is the gold standard in diagnostics. As a precaution, determination of the HbA1c and OGTT is recommended. It is not necessary to determinate antibodies in every new case of diabetes. In patients with a vague constellation of clinical picture diagnosis can be ensured by findings of uric ketones, BGA, IA-2- and GAD-antibodies and optionally C-peptide. Often T1DM is associated with PGAS. Therefore, once manifestation of diabetes is detected, screening autoimmune disorders is recommended directly and regularly every two years.

Emotional exhaustion-induced latent autoimmune diabetes in adults in a young lady: A CARE-compliant case report.

Latent autoimmune diabetes in adults (LADA) refers to an autoimmune disorder characterized with detectable islets antibodies in the early diagnosis and increased autoimmune beta-cell failure progression. Notably, this kind of diabetes seems to be confused with other phenotypic diabetes.

The relationship between iodine intake and the risk of thyroid cancer: A meta-analysis.

Thyroid cancer (TC) is the most common malignancy of the endocrine system. The relationship between iodine intake and TC risk is controversial always. We aim to figure out the relationship between iodine intake and TC using meta-analysis. Literature research in MEDLINE, Embase, China National Knowledge Infrastructure, and China BioMedicine was performed up to April 2016, searched for relevant case-control and cohort studies. The effect of iodine consumption on the risk of TC was assessed using the pooled odds ratio (OR) and 95% confidence interval (CI). The meta-analysis included 8 case-control studies (n = 4974; 2213 cases; 2761 controls). More than adequate or excess iodine intake (>300 μg/d) decreased the risk of TC (OR 0.74, 95% CI 0.60, 0.92). High consumption of saltwater fish or shellfish decreased the risk of TC (OR 0.72, 95% CI 0.55, 0.95; OR 0.70, 95% CI 0.52, 0.96; respectively). A higher intake of dietary iodine was as a protective factor for TC. However, the available data are very limited and more studies are required.

Hepatoprotective Properties of a Polyphenol-Enriched Fraction from Annona crassiflora Mart. Fruit Peel against Diabetes-Induced Oxidative and Nitrosative Stress.

A polyphenol-enriched fraction from Annona crassiflora fruit peel (Ac-Pef) containing chlorogenic acid, (epi)catechin, procyanidin B2, and caffeoyl-glucoside was investigated against hepatic oxidative and nitrosative stress in streptozotocin-induced diabetic rats. Serum biochemical parameters, hepatic oxidative and nitrosative status, glutathione defense system analysis, and in silico assessment of absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the main compounds of Ac-Pef were carried out. Ac-Pef treatment during 30 days decreased serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities, as well as hepatic lipid peroxidation, protein carbonylation and nitration, inducible nitric oxide synthase level, and activities and expressions of glutathione peroxidase, superoxide dismutase, and catalase. There were increases in antioxidant capacity, glutathione reductase activity, and reduced glutathione level. ADMET predictions of Ac-Pef compounds showed favorable absorption and distribution, with no hepatotoxicity. A. crassiflora fruit peel showed hepatoprotective properties, indicating a promising natural source of bioactive molecules for prevention and therapy of diabetes complications.

27th Meeting of the European Association for the Study of Diabetes Eye Complications Study Group (EASDec).

Abstracts will be available online on 25 May 2017.

Influence of environmental temperature on risk of gestational diabetes.

Cold-induced thermogenesis is known to improve insulin sensitivity, which may become increasingly relevant in the face of global warming. The aim of this study was to examine the relation between outdoor air temperature and the risk of gestational diabetes mellitus.

The Association Between Endocan Levels and Subclinical Atherosclerosis in Patients With Type 2 Diabetes Mellitus.

Proinflammatory conditions induced by circulating factors in diabetes play a pivotal role in endothelial dysfunction and related vascular complications. Endothelial cell-specific molecule-1 or endocan is a dermatan sulfate proteoglycan secreted primarily by the vascular endothelium. Although endocan has been shown to be a potential biomarker in coronary heart disease, its role in the pathogenesis of atherosclerosis (AS) in diabetes remains unclear. In this study, we investigated the correlation between serum endocan levels and subclinical AS in patients with type 2 diabetes mellitus (T2DM).