scholarly journals Paeonol, an Ingredient of Kamishoyosan, Reduces Intracellular Lipid Accumulation by Inhibiting Glucocorticoid Receptor Activity in 3T3-L1 Cells

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 309
Author(s):  
Masayuki Izumi ◽  
Takashi Yoshida ◽  
Takashi Nakamura ◽  
Minoru Wakamori
Keyword(s):  
Glucocorticoid Receptor ◽  
Promoter Activity ◽  
Metabolic Diseases ◽  
Early Stage ◽  
Dependent Manner ◽  
Triglyceride Accumulation ◽  
Increased Risk ◽  
Intracellular Lipid Accumulation ◽  
Moutan Cortex ◽  
Habitual Intake

Excessive triglyceride accumulation in lipid-metabolizing tissues is associated with an increased risk of a variety of metabolic diseases. Kamishoyosan (KSS) is a Kampo composed of 10 constituent herbs, and contains moutan cortex (MC) and paeonol (PN) as the major ingredient of MC. Here, we demonstrate the molecular mechanism underlying the effect of KSS on the differentiation of mouse preadipocytes (3T3-L1 cells). KSS inhibited the accumulation of triglycerides in a dose-dependent manner in 3T3-L1 cells that were induced to differentiate into adipocytes. We also found that MC and PN were responsible for the anti-adipogenetic effect of KSS and significantly suppressed the expression of CCAAT/enhancer-binding proteins-δ (C/EBP-δ) mRNA 3 days after the induction of differentiation. Thus, PN may contribute to the anti-adipogenetic property of MC in 3T3-L1 cells. In addition, PN inhibited dexamethasone (Dex)-induced glucocorticoid receptor (GR) promoter activity. Taken together, these results suggest that PN suppresses C/EBP-δ expression by inhibiting Dex-induced GR promoter activity at the early stage of differentiation and, consequently, delays differentiation into mature adipocytes. Our results suggest that the habitual intake of Kampo-containing PN contributes to the prevention of the onset of metabolic diseases by decreasing the excessive accumulation of triglycerides in lipid-metabolizing tissues.

scholarly journals Chinese Propolis Prevents Obesity and Metabolism Syndromes Induced by a High Fat Diet and Accompanied by an Altered Gut Microbiota Structure in Mice

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 959
Author(s):  
Yufei Zheng ◽  
Yuqi Wu ◽  
Lingchen Tao ◽  
Xi Chen ◽  
Trevor Joseph Jones ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Liver Weight ◽  
Dependent Manner ◽  
Male Mice ◽  
High Fat ◽  
16S Rrna Analysis ◽  
Triglyceride Accumulation ◽  
Chinese Propolis

The increasing incidence of obesity poses a great threat to public health worldwide. Recent reports also indicate the relevance of obesity in metabolic diseases. Chinese propolis (CP), as a well-studied natural nutraceutical, has shown a beneficial effect on alleviating diabetes mellitus. However, few studies have investigated the effect of CP on weight management and energy balance. We examined the beneficial effects of dietary CP on weight in high-fat diet-fed female and male mice and determined whether CP alters gut microbiota. In this study, dietary CP supplementation reduces body weight and improves insulin resistance in high-fat diet (HFD)-fed mice in a dose-dependent manner. CP treatment also reverses liver weight loss and triglyceride accumulation in association with hepatic steatosis. The 16S rRNA analysis of gut microbiota demonstrated that CP treatment modulates the composition in HFD-fed mice. Our study also suggests that male mice were more sensitive to CP treatment than female mice. Taken together, CP supplementation reduces weight gain and reverses gut microbiome dysbiosis induced by HFD. Further, the effects of CP treatment on metabolic biomarkers and microbiome structure differ by gender.

Duffy antigen / receptor for chemokines correlates with inflammatory reaction in rats with venous hypertension: implication for the pathogenesis of primary chronic venous disease

VASA ◽  
2014 ◽  
Vol 43 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Weibin Huang ◽  
Weiwei Qin ◽  
Lei Lv ◽  
Haoyv Deng ◽  
Hao Zhang ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Early Stage ◽  
Antigen Receptor ◽  
Venous Hypertension ◽  
Skin Tissue ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Dependent Manner ◽  
Time Points ◽  
Duffy Antigen

Background: Duffy antigen / receptor for chemokines (DARC) possesses high affinity for several chemokine subgroups of CC and CXC. Although DARC has been shown to play a role in many inflammatory diseases, its effect on chronic venous disease (CVD) remains unidentified. We explored whether the expression of DARC in skin tissue was activated under venous hypertension as well as the relationships between DARC and inflammation. Materials and methods: The inflammation in a rat model of venous hypertension caused by a femoral arterial-venous fistula (AVF) was studied. At specified intervals the pressure in the femoral veins was recorded within 42 days. Hindlimb skin specimens were harvested at different time points. The expressions of DARC, interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1) in skin tissue were examined. Mononuclear cells infiltrated in skin tissue were detected. Results: Femoral venous pressures in AVF groups increased significantly at different time points (P < 0.01). DARC was expressed in skin tissue and its expression level increased significantly in AVF groups from the 7nd day on and was enhanced in a time-dependent manner within 42 days (P < 0.05). Meanwhile, both MCP-1 and IL-8 had higher levels, accompanied by increased mononuclear cells infiltrating into skin tissue (P < 0.05). Conclusions: A rat AVF model which can maintain venous hypertension for at least 42 days is competent for researching the pathogenesis of CVD. DARC, which plays a role in the inflammation of skin tissue under venous hypertension, may become a new molecular target for diagnosis and treatment of CVD at a very early stage.

scholarly journals Glucolipotoxicity and GLP-1 secretion

2021 ◽  
Vol 9 (1) ◽  
pp. e001905
Author(s):  
Jung-Hee Hong ◽  
Dae-Hee Kim ◽  
Moon-Kyu Lee
Keyword(s):  
Glucose Transporter ◽  
Cell Function ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Gene Expressions ◽  
Simultaneous Treatment ◽  
L Cells ◽  
Triglyceride Accumulation

IntroductionThe concept of glucolipotoxicity refers to the combined, deleterious effects of elevated glucose and/or fatty acid levels.Research design and methodsTo investigate the effects of chronic glucolipotoxicity on glucagon-like peptide-1-(7-36) amide (GLP-1) secretion, we generated glucolipotoxic conditions in human NCI-H716 enteroendocrine cells using either 5 or 25 mM glucose with or without 500 µM palmitate for 72 hours. For in vivo study, we have established a chronic nutrient infusion model in the rat. Serial blood samples were collected for 2 hours after the consumption of a mixed meal to evaluate insulin sensitivity and β-cell function.ResultsChronic glucolipotoxic conditions decreased GLP-1 secretion and the expressions of pCREB, pGSK3β, β-catenin, and TCF7L2 in NCI-H716 cells. Glucolipotoxicity conditions reduced glucose transporter expression, glucose uptake, and nicotinamide-adenine dinucleotide phosphate (NADPH) levels in L-cells, and increased triglyceride accumulation. In contrast, PPARα and ATP levels were reduced, which correlated well with decreased levels of SUR1 and Kir6.2, cAMP contents and expressions of pCAMK2, EPAC and PKA. We also observed an increase in reactive oxygen species production, UCP2 expression and Complex I activity. Simultaneous treatment with insulin restored the GLP-1 secretion. Glucolipotoxic conditions decreased insulin secretion in a time-dependent manner in INS-1 cells, which was recovered with exendin-4 cotreatment. Glucose and SMOFlipid infusion for 6 hours decreased GLP-1 secretion and proglucagon mRNA levels as well as impaired the glucose tolerance, insulin and C-peptide secretion in rats.ConclusionThese results provide evidence for the first time that glucolipotoxicity could affect GLP-1 secretion through changes in glucose and lipid metabolism, gene expressions, and proglucagon biosynthesis and suggest the interrelationship between glucolipotoxicities of L-cells and β-cells which develops earlier than that of L-cells.

scholarly journals Adjuvant brachytherapy for FIGO stage I serous or clear cell endometrial cancer

2021 ◽  
pp. ijgc-2020-002217
Author(s):  
Elizabeth B Jeans ◽  
William G Breen ◽  
Trey C Mullikin ◽  
Brittany A Looker ◽  
Andrea Mariani ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Clear Cell ◽  
Early Stage ◽  
Figo Stage ◽  
Stage I ◽  
High Dose ◽  
Vaginal Cuff ◽  
Locoregional Failure ◽  
Platinum Based Chemotherapy ◽  
Increased Risk

ObjectivesOptimal adjuvant treatment for early-stage clear cell and serous endometrial cancer remains unclear. We report outcomes for women with surgically staged International Federation of Gynecology and Obstetrics (FIGO) stage I clear cell, serous, and mixed endometrial cancers following adjuvant vaginal cuff brachytherapy with or without chemotherapy.MethodsFrom April 1998 to January 2020, women with FIGO stage IA–IB clear cell, serous, and mixed endometrial cancer underwent surgery and adjuvant vaginal cuff brachytherapy. Seventy-six patients received chemotherapy. High-dose rate vaginal cuff brachytherapy was planned to a total dose of 21 gray in three fractions using a multichannel vaginal cylinder. The primary objective was to determine the effectiveness of adjuvant vaginal cuff brachytherapy and to identify surgicopathological risk factors that could portend towards worse oncological outcomes.ResultsA total of 182 patients were included in the analysis. Median follow-up was 5.3 years (2.3–12.2). Ten-year survival was 73.3%. Five-year cumulative incidence (CI) of vaginal, pelvic, and para-aortic relapse was 1.4%, 2.1%, and 0.9%, respectively. Five-year locoregional failure, any recurrence, peritoneal relapse, and other distant recurrence was 4.4%, 11.6%, 5.3%, and 6.7%, respectively. On univariate analysis, locoregional failure was worse for larger tumors (per 1 cm) (HR 1.9, 95% CI 1.2 to 3.0, p≤0.01). Any recurrence was worse for tumors of at least 3.5 cm (HR 3.8, 95% CI 1.3 to 11.7, p=0.02) and patients with positive/suspicious cytology (HR 4.4, 95% CI 1.5 to 12.4, p≤0.01). Ten-year survival for tumors of at least 3.5 cm was 56.9% versus 86.6% for those with smaller tumors (HR 2.9, 95% CI 1.4 to 5.8, p≤0.01). Ten-year survival for positive/suspicious cytology was 50.9% versus 77.4% (HR 2.2, 95% CI 0.9 to 5.4, p=0.09). Multivariate modeling demonstrated worse locoregional failure, any recurrence, and survival with larger tumors, as well as any recurrence with positive/suspicious cytology. Subgroup analysis demonstrated improved outcomes with the use of adjuvant chemotherapy in patients with large tumors or positive/suspicious cytology.ConclusionAdjuvant vaginal cuff brachytherapy alone without chemotherapy is an appropriate treatment for women with negative peritoneal cytology and small, early-stage clear cell, serous, and mixed endometrial cancer. Larger tumors or positive/suspicious cytology are at increased risk for relapse and worse survival, and should be considered for additional upfront adjuvant treatments, such as platinum-based chemotherapy.

scholarly journals Thrombomodulin is upregulated in the kidneys of women with pre-eclampsia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cleo C. L. van Aanhold ◽  
Manon Bos ◽  
Katrina M. Mirabito Colafella ◽  
Marie-Louise P. van der Hoorn ◽  
Ron Wolterbeek ◽  
...  
Keyword(s):  
Glomerular Filtration ◽  
Early Stage ◽  
Vascular Inflammation ◽  
Angiogenesis Inhibitor ◽  
Serum Levels ◽  
Dependent Manner ◽  
Glomerular Filtration Barrier ◽  
Soluble Thrombomodulin ◽  
Filtration Barrier ◽  
Glomerular Endothelium

AbstractThe endothelial glycoprotein thrombomodulin regulates coagulation, vascular inflammation and apoptosis. In the kidney, thrombomodulin protects the glomerular filtration barrier by eliciting crosstalk between the glomerular endothelium and podocytes. Several glomerular pathologies are characterized by a loss of glomerular thrombomodulin. In women with pre-eclampsia, serum levels of soluble thrombomodulin are increased, possibly reflecting a loss from the glomerular endothelium. We set out to investigate whether thrombomodulin expression is decreased in the kidneys of women with pre-eclampsia and rats exposed to an angiogenesis inhibitor. Thrombomodulin expression was examined using immunohistochemistry and qPCR in renal autopsy tissues collected from 11 pre-eclamptic women, 22 pregnant controls and 11 hypertensive non-pregnant women. Further, kidneys from rats treated with increasing doses of sunitinib or sunitinib in combination with endothelin receptor antagonists were studied. Glomerular thrombomodulin protein levels were increased in the kidneys of women with pre-eclampsia. In parallel, in rats exposed to sunitinib, glomerular thrombomodulin was upregulated in a dose-dependent manner, and the upregulation of glomerular thrombomodulin preceded the onset of histopathological changes. Selective ETAR blockade, but not dual ETA/BR blockade, normalised the sunitinib-induced increase in thrombomodulin expression and albuminuria. We propose that glomerular thrombomodulin expression increases at an early stage of renal damage induced by antiangiogenic conditions. The upregulation of this nephroprotective protein in glomerular endothelial cells might serve as a mechanism to protect the glomerular filtration barrier in pre-eclampsia.

scholarly journals De-escalation of radiation therapy in patients with stage I, node-negative, HER2-positive breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jose G. Bazan ◽  
Sachin R. Jhawar ◽  
Daniel Stover ◽  
Ko Un Park ◽  
Sasha Beyer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Local Therapy ◽  
Adjuvant Radiation ◽  
Her2 Positive ◽  
Node Negative ◽  
Risk Of Death ◽  
Her2 Breast Cancer ◽  
Neoadjuvant Systemic Therapy ◽  
Increased Risk

AbstractIn the modern era, highly effective anti-HER2 therapy is associated with low local-regional recurrence (LRR) rates for early-stage HER2+ breast cancer raising the question of whether local therapy de-escalation by radiation omission is possible in patients with small-node negative tumors treated with lumpectomy. To evaluate existing data on radiation omission, we used the National Cancer Database (NCDB) to test the hypothesis that RT omission results in equivalent overall survival (OS) in stage 1 (T1N0) HER2+ breast cancer. We excluded patients that received neoadjuvant systemic therapy. We stratified the cohort by receipt of adjuvant radiation. We identified 6897 patients (6388 RT; 509 no RT). Patients that did not receive radiation tended to be ≥70 years-old (odds ratio [OR] = 3.69, 95% CI: 3.02–4.51, p < 0.0001), to have ≥1 comorbidity (OR = 1.33, 95% CI: 1.06–1.68, p = 0.0154), to be Hispanic (OR = 1.49, 95% CI: 1.00–2.22, p = 0.049), and to live in lower income areas (OR = 1.32, 95% CI: 1.07–1.64, p = 0.0266). Radiation omission was associated with a 3.67-fold (95% CI: 2.23–6.02, p < 0.0001) increased risk of death. While other selection biases that influence radiation omission likely persist, these data should give caution to radiation omission in T1N0 HER2+ breast cancer.

scholarly journals The use of an in-vitro batch fermentation (human colon) model for investigating mechanisms of TMA production from choline, l-carnitine and related precursors by the human gut microbiota

2021 ◽  
Author(s):  
Priscilla Day-Walsh ◽  
Emad Shehata ◽  
Shikha Saha ◽  
George M. Savva ◽  
Barbora Nemeckova ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Human Colon ◽  
Human Studies ◽  
Bacterial Strains ◽  
Increased Risk ◽  
Carnitine Metabolism ◽  
Registration Number ◽  
Vitro Model

Abstract Purpose Plasma trimethylamine-N-oxide (TMAO) levels have been shown to correlate with increased risk of metabolic diseases including cardiovascular diseases. TMAO exposure predominantly occurs as a consequence of gut microbiota-dependent trimethylamine (TMA) production from dietary substrates including choline, carnitine and betaine, which is then converted to TMAO in the liver. Reducing microbial TMA production is likely to be the most effective and sustainable approach to overcoming TMAO burden in humans. Current models for studying microbial TMA production have numerous weaknesses including the cost and length of human studies, differences in TMA(O) metabolism in animal models and the risk of failing to replicate multi-enzyme/multi-strain pathways when using isolated bacterial strains. The purpose of this research was to investigate TMA production from dietary precursors in an in-vitro model of the human colon. Methods TMA production from choline, l-carnitine, betaine and γ-butyrobetaine was studied over 24–48 h using an in-vitro human colon model with metabolite quantification performed using LC–MS. Results Choline was metabolised via the direct choline TMA-lyase route but not the indirect choline–betaine-TMA route, conversion of l-carnitine to TMA was slower than that of choline and involves the formation of the intermediate γ-BB, whereas the Rieske-type monooxygenase/reductase pathway for l-carnitine metabolism to TMA was negligible. The rate of TMA production from precursors was choline > carnitine > betaine > γ-BB. 3,3-Dimethyl-1-butanol (DMB) had no effect on the conversion of choline to TMA. Conclusion The metabolic routes for microbial TMA production in the colon model are consistent with observations from human studies. Thus, this model is suitable for studying gut microbiota metabolism of TMA and for screening potential therapeutic targets that aim to attenuate TMA production by the gut microbiota. Trial registration number NCT02653001 (http://www.clinicaltrials.gov), registered 12 Jan 2016.

scholarly journals Phenotype of the Aging-Dependent Spontaneous Onset of Hearing Loss in DBA/2 Mice

2021 ◽  
Vol 8 (3) ◽  
pp. 49
Author(s):  
Min-Soo Seo ◽  
Byeonghyeon Lee ◽  
Kyung-Ku Kang ◽  
Soo-Eun Sung ◽  
Joo-Hee Choi ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Early Stage ◽  
Auditory Brainstem ◽  
Dependent Manner ◽  
Intrinsic Properties ◽  
Hearing Ability ◽  
Brainstem Response ◽  
Long Term Observation ◽  
Spontaneous Onset

DBA/2 mice are a well-known animal model for hearing loss developed due to intrinsic properties of these animals. However, results on the phenotype of hearing loss in DBA/2 mice have been mainly reported at an early stage in mice aged ≤7 weeks. Instead, the present study evaluated the hearing ability at 5, 13, and 34 weeks of age using DBA/2korl mice. Auditory brainstem response test was performed at 8–32 KHz at 5, 13, and 34 weeks of age, and hearing loss was confirmed to be induced in a time-dependent manner. In addition, histopathological evaluation at the same age confirmed the morphological damage of the cochlea. The findings presented herein are the results of the long-term observation of the phenotype of hearing loss in DBA/2 mice and can be useful in studies related to aging-dependent hearing loss.

scholarly journals Paternal smoking is associated with an increased risk of pregnancy loss in a dose-dependent manner: a systematic review and meta-analysis

F&S Reviews ◽  
2021 ◽  
Author(s):  
Nadia A. du Fossé ◽  
Marie-Louise P. van der Hoorn ◽  
Nina H. Buisman ◽  
Jan M.M. van Lith ◽  
S askia le Cessie ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pregnancy Loss ◽  
Meta Analysis ◽  
Dependent Manner ◽  
Increased Risk ◽  
Dose Dependent ◽  
Paternal Smoking
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