bluuebunny/crossref_metadata_2025_split huggingface dataset:
OR03-01 Effects Of Alpha-emitting Meta-211At-astato-benzylguanidine (211At-MABG) Compared To 131I-meta-iodobenzylguanidine (131I-MIBG) on Tumor Growth Suppression in a Pheochromocytoma Mouse Model
Authors: Yoshinaga Keiichiro , Zhao Songji , Washino Komei , Aoki Miho , Nishijima Ken-ichi , Shimoyama Saki , Ukon Naoyuki , Gao Fengying , Washiyama Kohshin , Ito Natsue , Yoshioka Naho , Tamura Naomi , Takahashi Kazuhiro , Ito Hiroshi , Higashi Tatsuya 
Published: May 2020

Abstract
Objectives: Given the limited treatment approaches currently available for patients with metastatic pheochromocytoma and paraganglioma (PPGL), new effective approaches are being sought. The radioisotope approach using 131I-meta-iodobenzylguanidine (131I-MIBG) has limited survival benefits in metastatic PPGL but is currently considered one of the standard therapeutic approaches. In theory, the alpha-emitting radiopharmaceutical meta-211At-astato-benzylguanidine (211At-MABG) could be a very effective targeted treatment for metastatic PPGL. However, this possibility has not been evaluated. Therefore, the purpose of this study was to evaluate the tumor growth suppression effects of 211At-MABG compared to 131I-MIBG using a PC-12 mouse pheochromocytoma model.
Methods: Rat pheochromocytoma (PC-12) cells were subcutaneously inoculated into male BALB/c nu/nu nude mice. When tumor volumes reached approximately 300 mm3, mice bearing PC-12 tumors received intravenously either 1.11 MBq of 211At-MABG (n=6), 31 MBq of 131I-MIBG (n=3) or vehicle solvent (n = 6). The tumor volume was measured 3 times per week for 2 weeks. The tumor volume was compared among the three groups.
Results: At 14 days, the tumor volumes significantly increased in the control group (328.82±83.65 to 3568.83±693.23 mm3, P&lt;0.001). In contrast, there were no significant changes in tumor volumes in the 211At-MABG group (284.65±56.77 to 274.3±87.95 mm3, P=0.616) and 131I-MIBG group (484.40±46.25 to 323.93±127.27 mm3, P=0.084). The 211At-MABG group showed significantly lower percentage change in tumor volume than did the control group (-5.0±15.99 vs. 1043.83±320.79%, P&lt;0.001), and 131I-MIBG group also showed significant volume reduction rate compared to that of the control group (-34.33±21.39 vs. 1043.82±320.79%, P&lt;0.001). There was no significant difference in percentage tumor volume changes between the 211At-MABG and 131I-MIBG groups (P=0.052). Conclusion: At 14 days after radiopharmaceutical administration, 211At-MABG produced significant tumor volume reduction as compared to that in the control group and to that associated with 131I-MIBG, which is considered one of the current treatment options. Therefore, 211At-MABG may have future clinical applications for the treatment of metastatic pheochromocytoma and paraganglioma.
OR20-03 Transcriptional Changes in Lipid Metabolism of Adipocytes Derived from Subcutaneous Abdominal Adipose Stem Cells of Normal-Weight Polycystic Ovary Syndrome Women
Authors: Leung Karen Lynn , Sanchita Smriti , Dumesic Phillip , Ding Xiangming , Li Xinmin , Morselli Marco , Pellegrini Matteo , Dumesic Daniel Anthony , Chazenbalk Gregorio Daniel 
Published: May 2020

Abstract
Normal-weight polycystic ovary syndrome (PCOS) women exhibit increased adipose insulin resistance in vivo (1) accompanying enhanced subcutaneous (SC) abdominal adipose stem cell (ASC) development to adipocytes with greater lipid accumulation per cell in vitro (2). To determine whether this phenomenon is associated with abnormal adipogenic gene transcription during ASC differentiation into adipocytes, SC abdominal ASCs isolated from three non-Hispanic Caucasian normal-weight PCOS women and three age- and BMI-matched controls were cultured in adipogenic differentiation medium for 3–12 days. After RNA isolation, gene expression levels were determined by RNA sequencing at days 3, 7, and 12. Differentially expressed genes were filtered for significance (padj&lt;0.05) and fold change (&gt;2-fold); upstream regulator genes and gene ontology (GO) functions were determined using Ingenuity Pathway Analysis. Gene set enrichment analysis (GSEA) also was used to identify enriched cellular processes (3). Differentially expressed genes in PCOS vs. control cells were either upregulated (466, 768 and 441 genes on days 3, 7 and 12, respectively) or downregulated (742, 974 and 605 genes on days 3, 7 and 12, respectively) over time, with critical genes governing adipocyte cell differentiation in PCOS cells increased 2–6 fold at days 3, 7 and 12 (PPARγ, CEBPα, ADIPOQ, AGPAT2, FABP4, LPL, PLIN1). The predicted upstream regulator genes TGFβ1 (an adipogenic inhibitor) and TNF (a pro-inflammatory adipokine) were significantly reduced in PCOS relative to control cells at all time points. The GO functions lipid oxidation and free fatty acid (FFA) beta-oxidation were enriched amongst upregulated genes in PCOS cells across all time points, while acylglycerol synthesis was increased at days 7 and 12 alone (z&gt;2, p&lt;0.05, all GO functions). In parallel, GSEA showed in PCOS cells significantly increased transcripts related to oxidative phosphorylation, peroxisome activity and adipogenesis at all time points (p&lt;0.05). Thus, adipocytes derived from SC abdominal ASCs of normal-weight PCOS women exhibit early activation of adipogenic genes, potentially underlying their exaggerated lipid accumulation in vitro, as previously described (2). These PCOS-related changes in gene expression involve an increase in both oxidative phosphorylation and FFA beta oxidation, which could disrupt the balance between energy production and lipid storage, particularly when caloric intake exceeds energy utilization. References: (1) Dumesic DA, et al JCEM 2019;104(6):2171–83; (2) Leung KL, et al. JES 2019;3:Supplement 1, SUN-107 (3) Subhramanian A, et al. PNAS 2005;102:43
SAT-739 Membrane Progesterone Receptors (mPRs/PAQRs) Promote Proliferation, Migration and Neurotrophin Expression in Schwann Cell-like Adipose Stem Cells, Potentially Improving Peripheral Nerve Regeneration
Authors: Castelnovo Luca F , Thomas Peter 
Published: May 2020

Abstract
Peripheral nerve injury is a problem affecting millions of people worldwide, causing significant disability and a reduction in the quality of life. The neurons of the peripheral nervous system are characterized by a significant regeneration capability. However, the functional recovery is unsatisfactory in most cases, making the identification of new strategies to improve the regenerative outcome a major medical need. Schwann cells (SCs), the main neuroglial cells of the peripheral nervous system, trans-differentiate after nerve injury towards a phenotype, known as the repair phenotype, that promotes nerve regeneration. Nonetheless, adult human SCs have poor expansion capability in vitro, undermining their potential clinical development. Several studies have shown that mesenchymal stem cells, especially when differentiated into a Schwann cell-like (SCL) phenotype, may represent an alternative to primary SCs, promoting pro-regenerative effects both in vitro and in vivo. Recently, membrane progesterone receptors (mPRs), members of the progestin and adipoQ receptor (PAQR) family, have been shown to be present and active in Schwann cells. Progesterone activates mPRs in SCs to promote cell migration and proliferation, change cell morphology, and modulate the expression of key SC differentiation factors. These findings suggest a possible role for mPRs in nerve repair. The goal of the present project is to study the role of mPRs in the promotion of pro-regenerative effects in mesenchymal adipose stem cells (ASC), both undifferentiated (uASC) and after differentiation toward the SCL phenotype (SCL-ASC). We first characterized uASC and SCL-ASC, confirming that the latter showed increased expression of SC markers like S100B, Sox10, GFAP, P0 and Krox20, alongside a more pronounced spindle-like shape leading to an increased aspect ratio. The differentiation protocol also increased mPR gene expression in SCL-ASC compared to uASC, especially mPRα (PAQR7) and mPRβ (PAQR8). Treatment with the specific mPR agonist Org OD 02-0 (02-0) caused cell elongation in SCL-ASC, mimicking what happens to SCs in vivo when they trans-differentiate towards the repair phenotype. 02-0 treatment also led to increased cell migration and cell proliferation in both uASC and SCL-ASC, consistent with a pro-regenerative role of mPRs. The effect was more rapid and evident in SCL-ASC. Lastly, we analyzed the effect of mPR activation on neutrophin production and release in uASC and SCL-ASC. A significant increase was observed in the expression and release of the brain derived neurotrophic factor (BDNF), whose role in promoting neurogenesis is well established. Our results support the hypothesis that mPRs have an important role in the modulation of uASC and SCL-ASC physiology and their activation may promote nerve regeneration.
OR02-02 Possible Age and Time-Of-Day Differences in the Hypothalamo-Pituitary-Testicular, and Adrenal, Response to Total Overnight Sleep Restriction
Authors: Liu Peter Y , Takahashi Paul , Yang Rebecca , Iranmanesh Ali , Veldhuis Johannes D 
Published: May 2020

Abstract
Introduction: In young men, sleep restriction decreases testosterone and increases afternoon cortisol, leading to anabolic-catabolic imbalance, insulin resistance and metabolic, neurocognitive, reproductive, and other adverse effects. Age-related differences in the hypothalamo-pituitary-testicular/adrenal response to sleep restriction could expose older individuals to greater or lesser risk, but this possibility has not been previously studied.
Subjects and Methods: Thirty-five healthy young and older men aged 18-30y (n=17) and 60-80y (n=18), underwent blood sampling in the Mayo Clinic Center for Clinical and Translational Science every 10 minutes for 24 hours from 6PM-6PM under two conditions in random order spaced at least 3 weeks apart: awake (no sleep) or sleep (from 10PM to 6AM). Blood was assayed for LH, testosterone (T) and cortisol (F), and then analyzed by automated mathematical deconvolution and with cross approximate entropy statistics to determine hormone secretion and hormone synchrony, respectively. Statistical significance was construed by repeated measures ANOVA using a full factorial model that included age, sleep and the interaction.
Results: Sleep deprivation had multiple effects on 24-hour (6PM-6PM) Te secretion with significant reductions in mean concentrations, basal, total and pulsatile secretion, and pulse frequency (each P&lt;0.05), in the absence of detectable changes in LH. These effects were most apparent in older men and differed according to age for some parameters: pulsatile Te secretion (P=0.03) and T pulse frequency (P=0.02). Time-of-day analyses revealed that sleep restriction significantly reduced Te in the morning (6AM-9AM) and afternoon (3PM-6PM), reduced LH in the morning, and increased F in the afternoon, particularly in older men. Cross-approximate entropy statistics showed that sleep restriction enforced greater LH-Te and Te-LH joint synchrony in the morning (P&lt;0.05 for each), but not in the afternoon.
Conclusion: Sleep restriction decreases morning LH secretion, morning and afternoon Te secretion, and increases afternoon F secretion, especially in older men. This combination of findings could plausibly cause metabolic and reproductive ill-health when accumulated over decades of life, and may explain how chronic sleep loss contributes to metabolic and reproductive diseases that are more prevalent in older men. These preliminary data also suggest a time-of-day dependent uncoupling of the regulatory control of the testicular axis, and of cortisol secretion. Direct verification by interventions that manipulate hormones during the morning and late afternoon in appropriately matched cohorts of young and older men are now required.
SAT-591 Lack of Adipose-Specific Hexose-6-Phosphate Dehydrogenase Improves Fat Metabolic Phenotype and Increases Insulin Sensitivity in Mice
Authors: Wang Jian , Wang Xinxiang , Kim Samuel , Liu Xiwen , Friedman Theodore C , Jiang Meisheng , Liu Yanjun 
Published: May 2020

Abstract
Lack of adipose-specific hexose-6-phosphate dehydrogenase improves fat metabolic phenotype and increases insulin sensitivity in mice.
ABSTRACT
Increased glucocorticoids (GCs) production in adipose tissue promotes the development of visceral obesity and the MS. The action of GCs in adipose tissue is tightly regulated by 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) coupled with hexose-6-phosphate dehydrogenase (H6PDH). However, the phenotypic consequences of reduction of fat-specific GC action caused by inactivation of H6PDH specifically in adipose tissue have not been explored. To better understand the physiological effects of adipose H6PDH, we generated a tissue-specific animal model of adipocyte-specific H6PDH deletion under the control of the murine adipocyte-specific adiponectin promoter (H6PDHAcKO mice). H6PDHAcKO mice exhibited complete absence of H6PDH expression and decreased GC production with reduction of 11β-HSD1 in adipose tissue. These mice had decreased abdominal fat mass with decreased adipose lipogenic gene expression associated with reduction of their transcription factor C/EBPs mRNA levels. Moreover, H6PDHAcKO mice also decreased adipose lipolysis and reduced plasma FFA levels. In addition, H6PDHAcKO mice decreased fasting glucose levels and increase tolerance to glucose and insulin. These data suggest that H6PDHAcKO mice may provide a good model for study the potential contribution of fat-specific H6PDH inhibition to improve the metabolic phenotype in vivo.
SUN-664 Effects of Acute Hyperglycemia on Monocytes in Type 2 Diabetes
Authors: Zhang Rong Mei , Oh Jisu , Lin Xiaobo , Arbelaez Ana Maria , Bernal-Mizrachi Carlos , Stone Pam 
Published: May 2020

Abstract
Background: Type 2 diabetes is linked to accelerated atherosclerosis, however the mechanisms behind this association are unclear. Inadequate glycemic control is an important contributor for cardiovascular disease (CVD). Episodic hyperglycemia as a surrogate for glycemic variability (GV) promotes monocyte adhesion and increases proinflammatory monocytes within plaques of patients with diabetes. Monocytes are precursors to macrophages which play a vital role in atherosclerosis and are capable of delivering cholesterol content to plaques. Therefore, elucidating the mechanism by which acute hyperglycemia promotes proatherogenic monocytes in diabetes can lead to novel therapies slowing atherosclerosis progression in these patients. Methods: To assess the effects of acute hyperglycemia on monocyte cholesterol metabolism, we isolated monocytes from 28 patients with Type 2 diabetes cultured for 2 and 6 hours in normoglycemic (90mg/dL) or hyperglycemic media (300mg/dL). Cholesterol content was measured by lipid extraction and fluorometric cholesterol oxidase assay. Cholesterol uptake was assessed by incubating monocytes with Dil-oxidized LDL (Dil-OxLDL). Cholesterol synthesis was performed by incubating monocytes with 2-14C-Acetate in both glycemic conditions for 6 hours followed by lipid saponification, and separated via TLC on silica gel plates. Cholesterol efflux was assessed by labeling cells with 3H-Cholesterol-OxLDL in both glycemic conditions for 6 hours followed by APO-A1 or HDL stimulation for 4 hours. Results: Acute hyperglycemia for 2 and 6 hours induced foamy monocytes with increased total cholesterol content (22 and 32%, respectively), cholesterol ester (40% and 43%, respectively), and free cholesterol content (14% and 25%, respectively) due to enhanced DiI-OxLDL uptake. There was no significant increase in monocyte cholesterol synthesis or cholesterol efflux after stimulation with HDL or APO A-1. Conclusions: Increased monocyte cholesterol content during acute hyperglycemia is a potential mechanism promoting atherosclerosis in patients with Type 2 diabetes.
SUN-655 Helicobacter Pylori Infection Is Not Associated with Diabetes Among a Cohort of Diabetic Patients in Alexandria City, Egypt
Authors: Amara Mohamed Fahmy 
Published: May 2020

Abstract
Abstract: Helicobacter Pylori infection is one of the most common bacterial infections in Egypt. A mounting body of evidence suggests the association of H Pylori infection with diabetes. H.Pylori is implicated in increasing insulin resistance and promoting chronic inflammation, resulting in the development of diabetes. This study aimed to estimate the prevalence of H.Pylori infection among a cohort of patients with diabetes in Alexandria city, Egypt and the possible role of this condition in the control of the glycemic profile. We also investigated the correlation between H.pylori infection and the presence of diabetes-related complications (diabetic nephropathy and retinopathy). The study was conducted on 300 subjects classified into three groups; Group (I): 100 patients with type 2 diabetes, Group (II): 100 subjects with type 1 diabetes, Group (III): 100 non-diabetic control subjects. Participants were subjected to detailed history taking and thorough clinical examination. Routine laboratory investigations were done, including HbA1c and fasting plasma glucose. Stool antigen test, on- site Helicobacter Pylori Ag Rapid Test-cassette was done. The mean duration of diabetes in type 2 diabetes was 8.18±5.87 years, while the mean duration in type 1 was 4.88± 3.02 years, which was statistically significante (p&lt; 0.05). The results of the presented study showed that there was no significant difference in the prevalence of Helicobacter Pylori infection between type 1 and type 2 patients with diabetes (31% Vs 38%, p=0.298), moreover; after adjustment for age, there was no significant difference in the prevalence of Helicobacter Pylori infection among either group with diabetes (Group 1 and group 2) compared to the control group, (p= 0.756 and 0.066) respectively. There was no statistically significant association between the presence of Helicobacter Pylori infection in both type 1 and type 2 diabetes, and an elevated HbA1c level above 6.5%.(p= 0.772 and p=0.524) respectively. The prevalence of diabetic nephropathy in patients with type 2 and type 1 diabetes was 5% and 3% respectively, which was non-statistically significant (p=0.721). While the prevalence of diabetic retinopathy was 11% among patients with type 2 compared to 1% among patients with type 1 diabetes, which was statistically significant (p=0.003). There was no statistically significant correlation between Helicobacter Pylori infection and the presence of diabetic nephropathy or diabetic retinopathy. Helicobacter Pylori infection was not associated with diabetes and did not affect the HbA1c level. Helicobacter Pylori infection was not correlated to the presence of either diabetic nephropathy or diabetic retinopathy among both patients with type 2 and type 1 diabetes.
Nothing to Disclose: MA, MM, AH
No Sources of Research Support
SAT-656 Both Neutrophil and Monocyte Ratios to High Density Lipoprotein Cholesterol Are Superior Biomarkers of Metabolic Syndrome
Authors: Ramakrishnan Neeraj , Jialal Ganesh , Jialal Ishwarlal 
Published: May 2020

Abstract
Metabolic Syndrome (MetS) continues to be a significant problem globally, affecting nearly 35% of adults in the USA. Whilst there is no ideal biomarker that captures this disorder high sensitivity C-reactive protein (hsCRP) is the most widely accepted measure.We examined the ratios between the phagocytes, neutrophils(PMN)and monocytes, to high density lipoprotein (HDL) and adiponectin, two anti-inflammatory proteins, in patients with nascent MetS without the confounding of T2DM, ASCVD, smoking or lipid therapy to determine if they were valid biomarkers of MetS. Patients with nascent MetS(n=58) and matched controls(n=44) were recruited from Sacramento County. Patients with diabetes, cardiovascular diseases, inflammation (hsCRP &gt;10mg/L or leukocytosis), smoking, anti-inflammatory and hypolipidemic drug therapies were excluded. Fasting blood samples were obtained for complete blood counts, basic metabolic panel, lipid profile, insulin adiponectin, leptin and chemerin. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from glucose and insulin levels. Ratios of PMN and monocytes to HDL-C and Adiponectin were calculated and compared statistically. PMN: HDL-C and Monocyte: HDL-C, increased in patients with MetS compared to controls (p&lt;0.0001 and p=0.001 respectively).Also the PMN: Adiponectin and monocyte: Adiponectin ratios were significantly increased in MetS (p=0.006 and 0.02 respectively). All ratios increased with increasing severity of MetS (p=0.01). Receiver Operating Characteristic (ROC) curve analysis showed that both the PMN/HDL-C and monocyte: HDL-C area under the curve(AUC)(0.85 and 0.84 respectively) significantly added to the CRP AUC(0.75), p=0.01 for both. Neither leukocyte: Adiponectin AUC was significant compared to hsCRP. Also both ratios to HDL-C correlated with cardio-metabolic features of MetS, hsCRP and insulin resistance(HOMA-IR) (p&lt;0.05). Whilst the PMN:HDL-C ratio correlated with leptin, and chemerin the monocyte: HDL-C ratio correlated significantly with chemerin only (p&lt;0.05) Our cross-sectional study indicates that ratios of neutrophils and monocytes to HDL-C are significantly increased in patients with nascent MetS, increase with severity of MetS, correlate positively with inflammation and insulin resistance and both ratios appear to be better predictors of MetS than hsCRP. In conclusion, they provide a cost-effective measure of Metabolic Syndrome and should be confirmed in larger data bases and prospective studies.