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targeted weight loss

Nienke M van Loon, Roelof Ottenhoff, Sander Kooijman, Martina Moeton, Saskia Scheij, Reinout L P Roscam Abbing, Marion J J Gijbels, Johannes H M Levels, Vincenzo Sorrentino, Jimmy F P Berbée, Patrick C N Rensen, Noam Zelcer
OBJECTIVE: The E3 ubiquitin ligase IDOL (inducible degrader of the LDLR [LDL (low-density lipoprotein) receptor]) is a post-transcriptional regulator of LDLR abundance. Model systems and human genetics support a role for IDOL in regulating circulating LDL levels. Whether IDOL plays a broader metabolic role and affects development of metabolic syndrome-associated comorbidities is unknown. APPROACH AND RESULTS: We studied WT (wild type) and Idol ( -/ - ) (Idol-KO) mice in 2 models: physiological aging and diet-induced obesity...
June 14, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Bo Hu, Nan Jiang, Qing Zhou, Sheng Cao, Shunji Gao, Binghong Zhang, Jinling Chen, Ruiqiang Guo
BACKGROUND: The thrombolysis in micro-circulation after acute myocardial infarction has been an unsolved issue, as elimination effect of acute thrombolysis and primary intervention were unsatisfied. Stable cavitation using acoustic phase-change nanoparticles may have potential for thrombolysis. Therefore, we sought to investigate a novel treatment method with dodecafluoropentane (DDFP) nanoparticles for rapid and effective thrombolysis in an in-vitro artificial vascular system, as a mimicking preparation of coronary circulation...
June 11, 2018: International Journal of Cardiology
J Uerlings, Z G Song, X Y Hu, S K Wang, H Lin, Johan Buyse, N Everaert
Dysfunction of the intestinal epithelial barrier under elevated temperatures is assumed to prompt pathological conditions and to eventually impede chickens' growth, resulting in massive economic losses in broiler industries. The aims of this research were to determine the impact of acute heat stress on the intestinal tight junction network of broiler chicks (Gallus domesticus L.) and to elucidate whether adenosine monophosphate-activated protein kinase (AMPK) was involved in the integrated response of the broiler's gastrointestinal tract to heat stress...
June 13, 2018: Poultry Science
Amel Dudakovic, Emily Camilleri, Christopher R Paradise, Rebekah M Samsonraj, Martina Gluscevic, Carlo Alberto Paggi, Dana L Begun, Farzaneh Khani, Oksana Pichurin, Farah S Ahmed, Ranya Elsayed, Mohammed Elsalanty, Meghan E McGee-Lawrence, Marcel Karperien, Scott M Riester, Roman Thaler, Jennifer J Westendorf, Andre J van Wijnen
Epigenetic mechanisms control skeletal development and osteoblast differentiation. Pharmacological inhibition of the histone 3 Lys-27 (H3K27) methyltransferase enhancer of zeste homolog 2 (Ezh2) in wildtype mice enhances osteogenesis and stimulates bone formation. However, conditional genetic loss of Ezh2 early in the mesenchymal lineage (i.e. through excision via Prrx1 promoter-driven Cre) causes skeletal abnormalities due to patterning defects. Here, we addressed the key question whether Ezh2 controls osteoblastogenesis at later developmental stages beyond patterning...
June 13, 2018: Journal of Biological Chemistry
Eun A Kang, Young Min Han, Jeong Min An, Yong Jin Park, Predrag Sikiric, Deok Hwan Kim, Kwang An Kwon, Yoon Jae Kim, Donghwa Yang, Hann Tchah, Ki Baik Hahm
Cancer cachexia, one of the metabolic syndromes caused by cancer, is a devastating and miserable condition encountered in more than 50% of terminal cancer patients presenting with significant weight loss associated with skeletal muscle atrophy and fat loss. Though cachexia may account for up to 20% of cancer deaths, no significant treatment is still lacking and is of urgent unmet medical need in cancer treatment. Therefore, understanding the underlying molecular mechanisms is essential for anticipating therapeutic approaches...
June 13, 2018: Current Pharmaceutical Design
Saranya Sridhar, Alexander Luedtke, Edith Langevin, Ming Zhu, Matthew Bonaparte, Tifany Machabert, Stephen Savarino, Betzana Zambrano, Annick Moureau, Alena Khromava, Zoe Moodie, Ted Westling, Cesar Mascareñas, Carina Frago, Margarita Cortés, Danaya Chansinghakul, Fernando Noriega, Alain Bouckenooghe, Josh Chen, Su-Peing Ng, Peter B Gilbert, Sanjay Gurunathan, Carlos A DiazGranados
Background In efficacy trials of a tetravalent dengue vaccine (CYD-TDV), excess hospitalizations for dengue were observed among vaccine recipients 2 to 5 years of age. Precise risk estimates according to observed dengue serostatus could not be ascertained because of the limited numbers of samples collected at baseline. We developed a dengue anti-nonstructural protein 1 (NS1) IgG enzyme-linked immunosorbent assay and used samples from month 13 to infer serostatus for a post hoc analysis of safety and efficacy...
June 13, 2018: New England Journal of Medicine
Ana I Duarte, Marie Sjögren, Maria S Santos, Catarina R Oliveira, Paula I Moreira, Maria Björkqvist
Neuronal loss alongside altered energy metabolism, are key features of Huntington's disease (HD) pathology. The orexigenic gut-peptide hormone ghrelin is known to stimulate appetite and affect whole body energy metabolism. Liraglutide is an efficient anti-type 2 diabetes incretin drug, with neuroprotective effects alongside anorectic properties. Combining liraglutide with the orexigenic peptide ghrelin may potentially promote brain/cognitive function in HD. The R6/2 mouse model of HD exhibits progressive central pathology, weight loss, deranged glucose metabolism, skeletal muscle atrophy and altered body composition...
June 12, 2018: Scientific Reports
Andrew Siref, Bonnie Balzer, Andrew Hendifar
A 63-year-old white man with no significant previous medical or surgical history presented with painless jaundice after 3 weeks of dark urine, yellow stools, and a 9-pound weight loss. Bilirubin, aspartate transaminase, alanine transaminase, and alkaline phosphatase were elevated, and a computed tomography scan detected a 10-cm, ill-defined mass at the porta hepatis compressing the common bile duct. He underwent endoscopic retrograde cholangiopancreatography with stenting and ultrasound-guided biopsies. Histologic sections showed a neoplastic population of small ovoid cells with a high N:C ratio, nuclear hyperchromasia, "smoky" chromatin and abundant mitotic figures, and characteristic of high-grade neuroendocrine carcinoma (HGNECA)...
June 7, 2018: American Journal of Dermatopathology
Kshitij Verma, Nehal Gupta, Tianzhu Zang, Phumvadee Wangtrakuldee, Sanjay K Srivastava, Trevor M Penning, Paul C Trippier
Aldo-keto reductase 1C3 (AKR1C3) also known as type 5 17 β-hydroxysteroid dehydrogenase is responsible for intratumoral androgen biosynthesis, contributing to the development of castration-resistant prostate cancer (CRPC) and eventual chemotherapeutic failure. Significant upregulation of AKR1C3 is observed in CRPC patient samples and derived CRPC cell lines. As AKR1C3 is a downstream steroidogenic enzyme synthesizing intratumoral testosterone (T) and 5α-dihydrotestosterone (DHT), the enzyme represents a promising therapeutic target to manage CRPC and combat the emergence of resistance to clinically employed androgen deprivation therapy...
June 11, 2018: Molecular Cancer Therapeutics
Gary W Liu, Alexander N Prossnitz, Diana G Eng, Yilong Cheng, Nithya Subrahmanyam, Jeffrey W Pippin, Robert J Lamm, Chayanon Ngambenjawong, Hamidreza Ghandehari, Stuart J Shankland, Suzie H Pun
Polymeric drug carriers can alter the pharmacokinetics of their drug cargoes, thereby improving drug therapeutic index and reducing side effects. Understanding and controlling polymer properties that drive tissue-specific accumulation is critical in engineering targeted drug delivery systems. For kidney disease applications, targeted drug delivery to renal cells that reside beyond the charge- and size-selective glomerular filtration barrier could have clinical potential. However, there are limited reports on polymer properties that might enhance kidney accumulation...
June 2, 2018: Biomaterials
Amilcare Barca, Francesca Gatti, Daniela Spagnolo, Stefania Ippati, Carla Vetrugno, Tiziano Verri
In excitable tissues, the endogenous dipeptide carnosine (CAR, β-Ala-l-His) sustains homeostatic responses to various challenges. By eliciting hypoglycemic effects via actions on the autonomic nervous system and protection of pancreatic beta-cells, CAR is also relevant in diabetes. We investigated the expression of genes involved in CAR biosynthesis, degradation, and membrane transport pathways, in the pancreas and brains of mice treated with streptozotocin (STZ) and then exposed to dietary CAR. We induced hyperglycemia by STZ intraperitoneal injections; then, STZ-treated mice received drinking water with or without CAR for two weeks...
June 9, 2018: International Journal of Molecular Sciences
Jodie M Dodd, Andrea R Deussen, Cecelia M O'Brien, Danielle A J M Schoenaker, Amanda Poprzeczny, Adrienne Gordon, Suzanne Phelan
Context: Many international clinical guidelines recommend that overweight and obese women lose weight prior to pregnancy to reduce the risk of adverse pregnancy outcomes. Women who have recently given birth and plan future pregnancies are an important target population for preconception weight-loss interventions. Objective: A systematic review to evaluate postpartum dietary and/or physical activity interventions to promote weight loss and improve health in a subsequent pregnancy was conducted...
June 7, 2018: Nutrition Reviews
Shachi Pranjal Vyas, Ritobrata Goswami
T helper cell subsets play a critical role in providing protection against offending pathogens by secreting specific cytokines. However, unrestrained T helper cell responses can promote chronic inflammation-mediated inflammatory diseases. Dysregulated T helper cell responses have been suggested to be involved in the pathogenesis of multiple inflammatory diseases, including allergic airway inflammation, rheumatoid arthritis, and inflammatory bowel disease (IBD) among others. Aberrant pro-inflammatory responses induced by Th1, Th2, and Th17 subsets are known to trigger IBD...
2018: Frontiers in Immunology
Simon Hohenester, Simon Christiansen, Jutta M Nagel, Ralf Wimmer, Renate Artmann, Gerald Denk, Monika Bischoff, Gert Bischoff, Christian Rust
Background The prevalence of obesity-related non-alcoholic fatty liver disease (NAFLD) is rising. NAFLD may result in non-alcoholic steatohepatitis (NASH), progressing to liver cirrhosis. Weight loss is recommended to treat obesity-related NASH. Lifestyle intervention may improve NASH. However, pertinent trials have so far focused on overweight patients, while patients with obesity are at highest risk of developing NAFLD. Furthermore, reports of effects on liver fibrosis are scarce. We evaluated the effect of lifestyle intervention on NAFLD in a real-life cohort of morbidly obese patients...
June 7, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Mohamed El Amraoui, Naoufal Hjira
Salmonelloses are bacterial infections of the faecal peril; they are endemic in some regions of the world. They can colonize almost any organ hematogenously, hence, severe forms may be observed. We report a case of typhoid fever in a 16-year old young adolescent with no medical history, sexually transmitted diseases or sexual intercourses, presenting with necrotic scrotal ulcerations evolving over the past 3 weeks in a context of fever, diarrhoea, weight loss and alteration of the general state. Paraclinical assessment showed 7g/dl hypochromic microcyticanemia with target cells in blood smear and normal hemoglobin electrophoresis, biologic inflammatory syndrome, malabsorption syndrome, cytolysis and hepatic cholestasis 20 times above the normal, hepatosplenomegaly, normal viral serologic testing (HBV, HCV, HIV, EBV and CMV) and positive testing for salmonella...
2018: Pan African Medical Journal
J Bábíčková, J Čonka, L Janovičová, M Boriš, B Konečná, R Gardlík
The aim of this study was to investigate the potential of extracellular DNA as a prognostic and/or therapeutic target in inflammatory bowel disease. Fifty male C57BL/6J mice were used in the experiment. Acute colitis was induced by intake of 2% dextran sulphate sodium (DSS) for seven days followed by three days of water intake. DNase I was injected intravenously on days 3 and 7. Plasmatic levels of extracellular DNA (ecDNA) were measured on days 6 and 10. Weight loss, stool consistency and liquid intake were monitored throughout the experiment...
2018: Folia Biologica (Praha)
Yuanwei Liang, Wei Huang, Delong Zeng, Xiaoting Huang, Leung Chan, Chaoming Mei, Pengju Feng, Choon-Hong Tan, Tianfeng Chen
Chemical drug design based on the biochemical characteristics of cancer cells has become an important strategy for discovery of novel anticancer drugs to enhance the cancer targeting effects and biocompatibility, and decrease toxic side effects. Camptothecin (CPT) demonstrated strong anticancer activity in clinical trials but also notorious adverse effects. In this study, we presented a smart targeted delivery system (Biotin-ss-CPT) that consists of cancer-targeted moiety (biotin), a cleavable disulfide linker (S-S bond) and the active drug CPT...
November 2018: Drug Delivery
Zhantong Wang, Orit Jacobson, Rui Tian, Ronnie C Mease, Dale Kiesewetter, Gang Niu, Martin G Pomper, Xiaoyuan Chen
Several radioligands targeting prostate-specific membrane antigen (PSMA) have been clinically introduced as a new class of radiotheranostics for the treatment of prostate cancer. Among them, (((R)-1-carboxy-2-mcercaptoethyl)carbamoyl)-L-glutamic acid (MCG) has been successfully labeled with radioisotopes for prostate cancer imaging. The aim of this study is to conjugate MCG with an albumin binding moiety to further improve the in vivo pharmacokinetics. METHODS: MCG was conjugated with an Evans blue (EB) derivative for albumin binding and a DOTA chelator...
June 4, 2018: Bioconjugate Chemistry
Cheng Zhang, Wei Rong, Guang-Hao Zhang, Ai-Hua Wang, Chang-Zhe Wu, Xiao-Lin Huo
Our previous study revealed that early application of electrical field stimulation (EFS) with the anode at the lesion and the cathode distal to the lesion reduced injury potential, inhibited secondary injury and was neuroprotective in the dorsal corticospinal tract after spinal cord injury (SCI). The objective of this study was to further evaluate the effect of EFS on protection of anterior horn motoneurons and their target musculature after SCI and its mechanism. Rats were randomized into three equal groups...
May 2018: Neural Regeneration Research
Marina Boix-Castejón, María Herranz-López, Alberto Pérez Gago, Mariló Olivares-Vicente, Nuria Caturla, Enrique Roche, Vicente Micol
TRIAL DESIGN: Plant-derived polyphenols have shown potential to alleviate obesity-related pathologies by a multi-targeted mechanism in animal models and human intervention studies. A dietary supplement based on a combination of Lippia citriodora (LC) and Hibiscus sabdariffa (HS) polyphenolic extracts was assayed in a double blind and placebo-controlled intervention study with 54 overweight subjects. METHODS: Blood pressure, body weight, height, triceps, biceps and abdominal skinfold thickness, and arm and abdominal circumferences were taken at the baseline, 30 and 60 days of the intervention period...
June 4, 2018: Food & Function
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