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دورية أكاديمية

Quantification of Aerosol Hydrofluoroalkane HFA-134a Elimination in the Exhaled Human Breath Following Inhaled Corticosteroids Administration.

المؤلفون: Shin, Hye-Won, Barletta, Barbara, Yoonessi, Leila, Meinardi, Simone, Leu, Szu-Yun, Radom-Aizik, Shlomit, Randhawa, Inderpal, Nussbaum, Eliezer, Blake, Donald R, Cooper, Dan M

المصدر: Clinical and translational science. 8(5)

مصطلحات موضوعية: Humans, Albuterol, Hydrocarbons, Fluorinated, Adrenal Cortex Hormones, Bronchodilator Agents, Aerosols, Aerosol Propellants, Breath Tests, Vital Capacity, Maximal Midexpiratory Flow Rate, Forced Expiratory Volume, Drug Monitoring, Administration, Inhalation, Predictive Value of Tests, Exhalation, Chemistry, Pharmaceutical, Adult, Middle Aged, California, Female, Male, Medication Adherence, Healthy Volunteers, Fluticasone, 1, 1, 1, 2-Tetrafluoroethane, Albuterol inhaler, HFA-134a, aerosol, asthma, bronchodilator, compliance, gas chromatography, hydrofluoroalkane, inhaled corticosteroids, propellant, Asthma, Lung, Clinical Research, Respiratory, Cardiorespiratory Medicine and Haematology, Oncology and Carcinogenesis, Other Medical and Health Sciences, General Clinical Medicine

الوصف: Inhaled corticosteroids (ICS) and β2-agonists are the primary pharmacotherapies of asthma management. However, suboptimal medication compliance is common in asthmatics and is associated with increased morbidity. We hypothesized that exhaled breath measurements of the aerosol used in the inhaled medications might prove useful as surrogate marker for asthma medication compliance. To explore this, 10 healthy controls were recruited and randomly assigned to ICS (Flovent HFA) or short acting bronchodilators (Proventil HFA). Both inhalers contain HFA-134a as aerosol propellant. Exhaled breath sampling and pulmonary function tests were performed prior to the inhaler medication dispersion, immediately after inhalation, then at 2, 4, 6, 8, 24, and 48 hours postadministration. At baseline, mean (SD) levels of HFA-134a in the breath were 252 (156) pptv. Immediately after inhalation, HFA-134a breath levels increased to 300 × 10(6) pptv and were still well above ambient levels 24 hours postadministration. The calculated ratio of forced expiratory volume in 1 second over forced vital capacity did not change over time following inhaler administration. This study demonstrates, for the first time, that breath HFA-134a levels can be used to assess inhaler medication compliance. It may also be used to evaluate how effectively the medicine is delivered.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8p4553j4Test

View record in eScholarship

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DUSP-1 Induced by PGE2 and PGE1 Attenuates IL-1β-Activated MAPK Signaling, Leading to Suppression of NGF Expression in Human Intervertebral Disc Cells

المؤلفون: Takuya Kusakabe, Yasunobu Sawaji, Kenji Endo, Hidekazu Suzuki, Takamitsu Konishi, Asato Maekawa, Kazuma Murata, Kengo Yamamoto

المصدر: International Journal of Molecular Sciences, Vol 23, Iss 371, p 371 (2022)
International Journal of Molecular Sciences; Volume 23; Issue 1; Pages: 371
International Journal of Molecular Sciences

مصطلحات موضوعية: Adult, MAP Kinase Signaling System, QH301-705.5, Interleukin-1beta, interleukin-1β (IL-1β), Catalysis, Article, Dinoprostone, Inorganic Chemistry, Nerve Growth Factor, Humans, mitogen-activated protein kinase (MAPK), Physical and Theoretical Chemistry, Alprostadil, Phosphorylation, RNA, Small Interfering, Biology (General), Intervertebral Disc, Molecular Biology, Protein Kinase Inhibitors, QD1-999, Spectroscopy, prostaglandin E2 (PGE2), Aged, Aged, 80 and over, intervertebral disc (IVD), dual-specificity phosphatase (DUSP)-1, Organic Chemistry, prostaglandin E1 (PGE1), Dual Specificity Phosphatase 1, General Medicine, Middle Aged, nerve growth factor (NGF), Computer Science Applications, Chemistry, lipids (amino acids, peptides, and proteins)

الوصف: The molecular mechanism of discogenic low back pain (LBP) involves nonphysiological nerve invasion into a degenerated intervertebral disc (IVD), induced by nerve growth factor (NGF). Selective cyclooxygenase (COX)-2 inhibitors are mainly used in the treatment of LBP, and act by suppressing the inflammatory mediator prostaglandin E2 (PGE2), which is induced by inflammatory stimuli, such as interleukin-1β (IL-1β). However, in our previous in vitro study using cultured human IVD cells, we demonstrated that the induction of NGF by IL-1β is augmented by a selective COX-2 inhibitor, and that PGE2 and PGE1 suppress NGF expression. Therefore, in this study, to elucidate the mechanism of NGF suppression by PGE2 and PGE1, we focused on mitogen-activated protein kinases (MAPKs) and its phosphatase, dual-specificity phosphatase (DUSP)-1. IL-1β-induced NGF expression was altered in human IVD cells by MAPK pathway inhibitors. PGE2 and PGE1 enhanced IL-1β-induced DUSP-1 expression, and suppressed the phosphorylation of MAPKs in human IVD cells. In DUSP-1 knockdown cells established using small interfering RNA, IL-1β-induced phosphorylation of MAPKs was enhanced and prolonged, and NGF expression was significantly enhanced. These results suggest that PGE2 and PGE1 suppress IL-1β-induced NGF expression by suppression of the MAPK signaling pathway, accompanied by increased DUSP-1 expression.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b7c9a5ccf41d6c8a632ab8a38c2612f2Test
https://www.mdpi.com/1422-0067/23Test/1/371

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Long noncoding RNA NEAT1 inhibits the acetylation of PTEN through the miR-524-5p /HDAC1 axis to promote the proliferation and invasion of laryngeal cancer cells

المؤلفون: Jiajia Zhang, Yanli Cui, Ping Wang

المصدر: Aging (Albany NY)

الوصف: Long noncoding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) is abnormally expressed in numerous tumors and functions as an oncogene, but the role of NEAT1 in laryngocarcinoma is largely unknown. Our study validated that NEAT1 expression was markedly upregulated in laryngocarcinoma tissues and cells. Downregulation of NEAT1 dramatically suppressed cell proliferation and invasion through inhibiting miR-524-5p expression. Additionally, NEAT1 overexpression promoted cell growth and metastasis, while overexpression of miR-524-5p could reverse the effect. NEAT1 increased the expression of histone deacetylase 1 gene (HDAC1) via sponging miR-524-5p. Mechanistically, overexpression of HDAC1 recovered the cancer-inhibiting effects of miR-524-5p mimic or NEAT1 silence by deacetylation of tensin homolog deleted on chromosome ten (PTEN) and inhibiting AKT signal pathway. Moreover, in vivo experiments indicated that silence of NEAT1 signally suppressed tumor growth. Taken together, knockdown of NEAT1 suppressed laryngocarcinoma cell growth and metastasis by miR-524-5p/HDAC1/PTEN/AKT signal pathway, which provided a potential therapeutic target for laryngocarcinoma.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aa292159c94bfaa2bef039575bf723c2Test
http://europepmc.org/articles/PMC8660614Test

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Comparative clinical outcomes of insulin degludec and insulin glargine 300 U/mL after switching from other basal insulins in real‐world patients with type 1 and type 2 diabetes

المؤلفون: Yukiko Hasegawa, Tetsuya Babazono, Junko Oya, Aki Katamine, Tomoko Nakagami, Yuichiro Kondo

المصدر: Journal of Diabetes Investigation, Vol 12, Iss 11, Pp 1983-1991 (2021)
Journal of Diabetes Investigation

مصطلحات موضوعية: Insulin degludec, Male, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Insulins, Insulin Glargine, Type 2 diabetes, 030204 cardiovascular system & hematology, Body Mass Index, chemistry.chemical_compound, 0302 clinical medicine, Japan, Drug Substitution, Insulin glargine 300 U/mL, General Medicine, Articles, Middle Aged, Insulin, Long-Acting, Treatment Outcome, Clinical Science and Care, Female, Original Article, medicine.drug, Adult, medicine.medical_specialty, 030209 endocrinology & metabolism, Real‐world clinical setting, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Aged, Retrospective Studies, Glycated Hemoglobin, Type 1 diabetes, Insulin glargine, business.industry, Insulin, medicine.disease, RC648-665, Endocrinology, Diabetes Mellitus, Type 1, Logistic Models, Basal (medicine), chemistry, Diabetes Mellitus, Type 2, Glycated hemoglobin, business

الوصف: Aims/Introduction To evaluate and compare the efficacy of insulin degludec (IDeg) and insulin glargine 300 U/mL (Gla300) 6 months after switching from other basal insulins by assessing the changes in glycated hemoglobin (HbA1c), body mass index (BMI), and insulin doses in patients with type 1 and type 2 diabetes in a real‐world clinical setting. Materials and Methods A total of 307 patients with type 1 diabetes and 294 patients with type 2 diabetes with HbA1c >7.0% were studied. Adjusted mean changes in HbA1c, BMI, and insulin doses were compared between IDeg (IDeg group) and Gla300 (Gla300 group) switchers. Multivariable logistic regression analyses were carried out to examine whether the IDeg or Gla300 group was associated with HbA1c or insulin dose reduction and BMI gain. Results HbA1c was significantly decreased in both the IDeg and Gla300 groups. Adjusted mean changes in HbA1c (approximately −0.3% and −0.5% in type 1 diabetes and type 2 diabetes patients, respectively) and BMI were similar between both groups. The mean change in insulin dose was slightly larger for dose reduction in the IDeg group than in the Gla300 group. Multivariable logistic regression models showed that the IDeg group was significantly associated with insulin dose reduction after adjusting for basal insulin type, insulin dose, and number of basal insulin injections at baseline and other confounding factors. Conclusions The current study suggested that IDeg and Gla300 have similar effects in reducing HbA1c and gaining BMI after switching from other basal insulins in Japanese patients with type 1 diabetes and type 2 diabetes. IDeg selection was associated with insulin dose reduction.
Insulin degludec and insulin glargine 300 U/mL showed similar values of reduction in glycated hemoglobin with body mass index almost unchanged 6 months after switching from other basal insulins in both type 1 and type 2 diabetes patients. Switching to insulin degludec was significantly associated with a reduction of basal and total insulin doses in both type 1 and type 2 diabetes patients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cd8e343952d329f98d4b6977a3a8fce5Test
https://doaj.org/article/33e2f17798204034beea375b21f2d506Test

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Novel glycoproteins identify preclinical atherosclerosis among women with previous preeclampsia regardless of type 1 diabetes status

المؤلفون: Marga Giménez, Eva López, Irene Vinagre, Eva Meler, Antonio J. Amor, Ignacio Conget, Verónica Perea, Maite Valverde, Laura Codina, Maria J. Barahona, Núria Alonso, Xavier Urquizu

المصدر: Nutrition, Metabolism and Cardiovascular Diseases. 31:3407-3414

الوصف: Background and aims Information regarding inflammation and cardiovascular disease (CVD) risk in type 1 diabetes (T1D) or preeclampsia (PE) is scarce. We assessed differences in inflammation markers according to the presence of both conditions and their association with atherosclerosis. Methods and results We recruited 112 women without CVD and last pregnancy ≥5 years previously (n = 28 per group): a)T1D and PE; b)T1D without PE; c)PE without T1D; and d)Controls (without T1D or PE). Groups were matched by several CVD risk factors, and diabetes duration and retinopathy in T1D. Carotid intima-media thickness (IMT) and plaque presence (IMT ≥1.5 mm) were assessed by ultrasonography. Inflammatory markers included classical variables (leucocytes and high-sensitivity C-reactive protein [hsCRP]) and glycoproteins by nuclear magnetic resonance (1H-NMR) spectroscopy (GlycA, GlycB, GlycF and the height/width [H/W] ratios of GlycA and GlycB). The age of the participants was 44.9 ± 7.8 years, and 20.5% harbored plaque. There were no differences in inflammatory markers among the four study groups. Overall, in multivariate-adjusted models, all 1H-NMR-glycoproteins (except GlycB) were positively associated with IMT measures (IMT of bulb and maximum-IMT of any carotid segment; p Conclusions High 1H-NMR-glycoprotein concentrations have a negative impact on carotid atherosclerosis among women with preeclampsia, regardless of T1D status.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fcedeb23bc8d78ef283a973fbc8f4f2fTest
https://doi.org/10.1016/j.numecd.2021.08.041Test

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SphK1‐driven autophagy potentiates focal adhesion paxillin‐mediated metastasis in colorectal cancer

المؤلفون: Zhihai Liang, Er-Dan Wei, Li-Ye Zhu, Shi-Quan Liu, Lan Lin, Shibo Luo, Jie-An Huang, Jiangni Wu, Xinze Qiu, Mengbin Qin, Da Chen, Zhenhua Fu

المصدر: Cancer Medicine
Cancer Medicine, Vol 10, Iss 17, Pp 6010-6021 (2021)

مصطلحات موضوعية: Adult, Male, Cancer Research, autophagy, Colorectal cancer, sphingosine kinase 1, Mice, Nude, Vimentin, colorectal cancer, macromolecular substances, environment and public health, Metastasis, Focal adhesion, Mice, medicine, Animals, Humans, Radiology, Nuclear Medicine and imaging, Neoplasm Metastasis, metastases, neoplasms, Paxillin, RC254-282, Research Articles, Cancer Biology, Aged, Aged, 80 and over, paxillin, Focal Adhesions, biology, Chemistry, Autophagy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Middle Aged, medicine.disease, digestive system diseases, Phosphotransferases (Alcohol Group Acceptor), Oncology, Sphingosine kinase 1, Cancer research, biology.protein, Immunohistochemistry, Female, Colorectal Neoplasms, Research Article

الوصف: Invasion and metastasis are the main causes of colorectal cancer (CRC)‐related death. Accumulating evidence suggested that sphingosine kinase 1 (SphK1) promoted the metastasis of CRC and autophagy played an important role in SphK1 promoting the metastasis of malignancy. However, the mechanism by which SphK1‐driven autophagy promotes invasion and metastasis in CRC remains to be clarified. In the present study, immunohistochemical detection showed the expression of SphK1 and paxillin was higher in human CRC tissues than those of normal colorectal mucosal tissues, they were both associated with TNM staging, lymphatic, and distance metastasis. In addition, study of in situ tumor transplantation model in nude mice showed that the suppression of SphK1 inhibited the growth of colonic orthotopic implantation tumors and the expression of paxillin, p‐paxillin, LC3 in the tumor. So, SphK1 may promote CRC metastasis via inducing the expression of paxillin expression and its phosphorylation, in vivo. Furthermore, results of CCK8 assay, transwell and wound healing assays showed that SphK1 promoted the viability, invasion, and metastasis of CRC cells. Transmission electron microscopy detection showed that SphK1 is the key factor in autophagy induction in CRC cells. Moreover, western blot examination indicated that the expression of LC3Ⅱ/Ⅰ, paxillin, p‐paxillin, MMP‐2, and vimentin was enhanced in SphK1‐overexpressed CRC cells and suppressed in SphK1 knockdown CRC cells, meanwhile, the expression of E‐cadherin was suppressed in SphK1‐overexpressed CRC cells and enhanced in SphK1 knockdown CRC cells. Suppression of autophagy by 3MA reversed the expression of paxillin and its phosphorylation in SphK1‐overexpressed CRC cells, indicated that SphK1‐driven autophagy induced the expression of paxillin and its phosphorylation in CRC cells. Together, these findings reveal that SphK1‐driven autophagy may promote the invasion and metastasis of CRC via promoting the expression of focal adhesion paxillin and its phosphorylation.
SphK1‐driven autophagy may promote the invasion and metastasis of CRC via promoting of the expression of focal adhesion paxillin and its phosphorylation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2b6b2bae84bdf5ef70cc291fbe7798e5Test
http://europepmc.org/articles/PMC8419751Test

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MMP‐7 affects peritoneal ultrafiltration associated with elevated aquaporin‐1 expression via MAPK/ERK pathway in peritoneal mesothelial cells

المؤلفون: Jun Ai, Gong Nirong, Daming Zuo, Fen Zhang, Zhuojun Zheng, Zhiwen Xiao, Qiaomu Yang, Yue Yin, Jia Zhou

المصدر: Journal of Cellular and Molecular Medicine

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, MAPK/ERK pathway, MAP Kinase Signaling System, Cell osmotic pressure, Cellular homeostasis, Matrix metalloproteinase, Epithelium, Cell Line, 03 medical and health sciences, Peritoneal cavity, 0302 clinical medicine, Osmotic Pressure, medicine, Extracellular, Humans, matrix metalloproteinases‐7, peritoneal membrane dysfunction, Peritoneal Cavity, Cells, Cultured, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Aquaporin 1, Chemistry, Epithelial Cells, Original Articles, Cell Biology, Middle Aged, Cell biology, 030104 developmental biology, medicine.anatomical_structure, aquaporin‐1, Matrix Metalloproteinase 7, 030220 oncology & carcinogenesis, Peritoneal Absorption, ultrafiltration failure, Molecular Medicine, Original Article, Female, extracellular signal‐regulated kinase, Peritoneal Dialysis, Mesothelial Cell, Homeostasis

الوصف: Peritoneal membrane dysfunction and the resulting ultrafiltration failure are the major disadvantages of long‐term peritoneal dialysis (PD). It becomes increasingly clear that mesothelial cells play a vital role in the pathophysiological changes of the peritoneal membrane. Matrix metalloproteinases (MMPs) function in the extracellular environment of cells and mediate extracellular matrix turnover during peritoneal membrane homeostasis. We showed here that dialysate MMP‐7 levels markedly increased in the patients with PD, and the elevated MMP‐7 level was negatively associated with peritoneal ultrafiltration volume. Interestingly, MMP‐7 could regulate the cell osmotic pressure and volume of human peritoneal mesothelial cells. Moreover, we provided the evidence that MMP‐7 activated mitogen‐activated protein kinases (MAPKs)‐extracellular signal‐regulated kinase 1/2 (ERK) pathway and subsequently promoted the expression of aquaporin‐1 (AQP‐1) resulting in the change of cell osmotic pressure. Using a specific inhibitor of ERK pathway abrogated the MMP‐7‐mediating AQP‐1 up‐regulation and cellular homeostasis. In summary, all the findings indicate that MMP‐7 could modulate the activity of peritoneal cavity during PD, and dialysate MMP‐7 might be a non‐invasive biomarker and an alternative therapeutic target for PD patients with ultrafiltration failure.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f61f848708457c8b4035d75baa6936e2Test
https://doi.org/10.1111/jcmm.16697Test

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Quantification of glycoproteins by nuclear magnetic resonance associated with preclinical carotid atherosclerosis in patients with type 1 diabetes

المؤلفون: Jesús Blanco, Sabina Ruiz, Monserrat Cofán, Marga Giménez, Irene Vinagre, Emilio Ortega, Verónica Perea, Ignacio Conget, Adriana Pané, Tonet Serés-Noriega, Enric Esmatjes, Alex Mesa, Antonio J. Amor

المصدر: Nutrition, Metabolism and Cardiovascular Diseases. 31:2099-2108

مصطلحات موضوعية: Adult, Carotid Artery Diseases, Male, Proteomics, Proton Magnetic Resonance Spectroscopy, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), 030209 endocrinology & metabolism, Inflammation, Disease, 030204 cardiovascular system & hematology, Carotid Intima-Media Thickness, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, Nuclear magnetic resonance, Predictive Value of Tests, medicine, Humans, In patient, Risk factor, Glycoproteins, chemistry.chemical_classification, Type 1 diabetes, Nutrition and Dietetics, business.industry, Carotid ultrasonography, Middle Aged, medicine.disease, Cross-Sectional Studies, Diabetes Mellitus, Type 1, chemistry, Asymptomatic Diseases, Female, Inflammation Mediators, medicine.symptom, Cardiology and Cardiovascular Medicine, Glycoprotein, business, Biomarkers

الوصف: Background and aims Glycoproteins play a key role in inflammatory and cardiometabolic processes. Their implication in atherosclerosis in type 1 diabetes (T1D) is unknown. We assessed the relationships between classic inflammatory markers, glycoproteins measured by nuclear magnetic resonance (1H-NMR), and preclinical atherosclerosis in these patients. Methods and results We selected patients with T1D, without cardiovascular disease (CVD), with: age ≥40 years, nephropathy (micro/macroalbuminuria), or ≥10 years of evolution with another risk factor. The presence of plaque (intima-media thickness >1.5 mm) was determined by ultrasonography. Concentrations of high-sensitive C-reactive protein (hsCRP), circulating leukocytes (classical inflammation markers) and 1H-NMR-glycoproteins (GlycA, GlycB, GlycF, and the height/width [H/W] ratios of GlycA and GlycB) were determined. We included 189 patients (58% male, age 47.0 [40.7–55.2] years). Thirty-five percent presented plaques (22%, ≥2 plaques). There was no association between hsCRP or leukocytes and atherosclerosis. However, in age- and sex-adjusted models, GlycA, GlycF, and the H/W ratios of GlycA and GlycB gradually increased with the number of plaques (0, 1, ≥2 plaques) only in patients without statins (p Conclusion In T1D individuals without lipid-lowering treatment, 1H-NMR-glycoproteins were independently associated with the presence and amount of carotid atherosclerosis, unlike other classical inflammatory markers. Further studies are needed to ascertain their utility as CVD biomarkers.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f07679a8dcf78fc872d100407689d8ffTest
https://doi.org/10.1016/j.numecd.2021.03.021Test

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Metabolomics Profiling of Patients With A−β+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis

المؤلفون: Kelly Rogers Keene, Farook Jahoor, Ruchi Gaba, Sanjeet Patel, Surya N. Mulukutla, Rasmus Bennet, Eunice I. Caducoy, Paras B. Mehta, Ashok Balasubramanyam, Åke Lernmark, W. Frank Peacock, Jean W. Hsu

المصدر: Diabetes

الوصف: When stable and near-normoglycemic, patients with “A−β+” ketosis-prone diabetes (KPD) manifest accelerated leucine catabolism and blunted ketone oxidation, which may underlie their proclivity to develop diabetic ketoacidosis (DKA). To understand metabolic derangements in A−β+ KPD patients during DKA, we compared serum metabolomics profiles of adults during acute hyperglycemic crises, without (n = 21) or with (n = 74) DKA, and healthy control subjects (n = 17). Based on 65 kDa GAD islet autoantibody status, C-peptide, and clinical features, 53 DKA patients were categorized as having KPD and 21 type 1 diabetes (T1D); 21 nonketotic patients were categorized as having type 2 diabetes (T2D). Patients with KPD and patients with T1D had higher counterregulatory hormones and lower insulin-to-glucagon ratio than patients with T2D and control subjects. Compared with patients withT2D and control subjects, patients with KPD and patients with T1D had lower free carnitine and higher long-chain acylcarnitines and acetylcarnitine (C2) but lower palmitoylcarnitine (C16)-to-C2 ratio; a positive relationship between C16 and C2 but negative relationship between carnitine and β-hydroxybutyrate (BOHB); higher branched-chain amino acids (BCAAs) and their ketoacids but lower ketoisocaproate (KIC)-to-Leu, ketomethylvalerate (KMV)-to-Ile, ketoisovalerate (KIV)-to-Val, isovalerylcarnitine-to-KIC+KMV, propionylcarnitine-to-KIV+KMV, KIC+KMV-to-C2, and KIC-to-BOHB ratios; and lower glutamate and 3-methylhistidine. These data suggest that during DKA, patients with KPD resemble patients with T1D in having impaired BCAA catabolism and accelerated fatty acid flux to ketones—a reversal of their distinctive BCAA metabolic defect when stable. The natural history of A−β+ KPD is marked by chronic but varying dysregulation of BCAA metabolism.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2758a0d78c43e7f8562a1a2ccfb706d0Test
https://doi.org/10.2337/db21-0066Test

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Parathyroid hormone receptor stimulation induces human adipocyte lipolysis and browning

المؤلفون: Niels Jessen, Bjørn Richelsen, Steen B. Pedersen, Peter Breining, Jacob B. Hansen, Mads Kjolby

المصدر: Breining, P, Pedersen, S B, Kjolby, M, Hansen, J B, Jessen, N & Richelsen, B 2021, ' Parathyroid hormone receptor stimulation induces human adipocyte lipolysis and browning ', European Journal of Endocrinology, vol. 184, no. 5, pp. 687-697 . https://doi.org/10.1530/EJE-20-0713Test

مصطلحات موضوعية: Adult, Male, endocrine system, medicine.medical_specialty, Adipose Tissue, Brown/metabolism, Lipolysis, Endocrinology, Diabetes and Metabolism, Receptor expression, Parathyroid hormone, Adipose tissue, Parathyroid Hormone/pharmacology, 030209 endocrinology & metabolism, White adipose tissue, Lipolysis/drug effects, Adipose Tissue/drug effects, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Adipose Tissue, Brown, Receptor, Parathyroid Hormone, Type 1/metabolism, Adipocyte, Internal medicine, Brown adipose tissue, Adipocytes, medicine, Humans, Uncoupling Protein 1, Receptor, Parathyroid Hormone, Type 1, Aged, Chemistry, Thermogenesis/drug effects, Thermogenesis, Uncoupling Protein 1/metabolism, General Medicine, Middle Aged, Thermogenin, Cross-Sectional Studies, medicine.anatomical_structure, Adipose Tissue, Parathyroid Hormone, 030220 oncology & carcinogenesis, Female, hormones, hormone substitutes, and hormone antagonists, Adipocytes/drug effects

الوصف: Objective Activation of brown adipose tissue is a promising strategy to treat and prevent obesity and obesity-related disorders. Activation of uncoupling protein 1 (UCP1) leads to uncoupled respiration and dissipation of stored energy as heat. Induction of UCP1-rich adipocytes in white adipose tissue, a process known as ‘browning’, serves as an alternative strategy to increase whole body uncoupling capacity. Here, we aim to assess the association between parathyroid hormone (PTH) receptor expression and UCP1 expression in human adipose tissues and to study PTH effects on human white and brown adipocyte lipolysis and UCP1 expression. Design A descriptive study of human neck adipose tissue biopsies substantiated by an interventional study on human neck-derived adipose tissue cell models. Methods Thermogenic markers and PTH receptor gene expression are assessed in human neck adipose tissue biopsies and are related to individual health records. PTH-initiated lipolysis and thermogenic gene induction are assessed in cultured human white and brown adipocyte cell models. PTH receptor involvement is investigated by PTH receptor silencing. Results PTH receptor gene expression correlates with UCP1 gene expression in the deep-neck adipose tissue in humans. In cell models, PTH receptor stimulation increases lipolysis and stimulates gene transcription of multiple thermogenic markers. Silencing of the PTH receptor attenuates the effects of PTH indicating a direct PTH effect via this receptor. Conclusion PTH 1 receptor stimulation by PTH may play a role in human adipose tissue metabolism by affecting lipolysis and thermogenic capacity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b9393d6212f2abdcb21a7db48ea58f29Test
https://doi.org/10.1530/eje-20-0713Test

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