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https://www.readbyqxmd.com/read/28817671/immunohistochemical-analysis-reveals-variations-in-proteasome-tissue-expression-in-c-elegans
#1
Elisa Mikkonen, Caj Haglund, Carina I Holmberg
The ubiquitin-proteasome system (UPS) plays a crucial part in normal cell function by mediating intracellular protein clearance. We have previously shown that UPS-mediated protein degradation varies in a cell type-specific manner in C. elegans. Here, we use formalin-fixed, paraffin-embedded C. elegans sections to enable studies on endogenous proteasome tissue expression. We show that the proteasome immunoreactivity pattern differs between cell types and within subcellular compartments in adult wild-type (N2) C...
2017: PloS One
https://www.readbyqxmd.com/read/28815409/insulin-like-growth-factor-igf-pathway-targeting-in-cancer-role-of-the-igf-axis-and-opportunities-for-future-combination-studies
#2
Aaron Simpson, Wilfride Petnga, Valentine M Macaulay, Ulrike Weyer-Czernilofsky, Thomas Bogenrieder
Despite a strong preclinical rationale for targeting the insulin-like growth factor (IGF) axis in cancer, clinical studies of IGF-1 receptor (IGF-1R)-targeted monotherapies have been largely disappointing, and any potential success has been limited by the lack of validated predictive biomarkers for patient enrichment. A large body of preclinical evidence suggests that the key role of the IGF axis in cancer is in driving treatment resistance, via general proliferative/survival mechanisms, interactions with other mitogenic signaling networks, and class-specific mechanisms such as DNA damage repair...
August 16, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28813700/regenerative-medicine-approaches-for-age-related-muscle-loss-and-sarcopenia-a-mini-review
#3
Juan Diego Naranjo, Jenna L Dziki, Stephen F Badylak
Sarcopenia is a complex and multifactorial disease that includes a decrease in the number, structure and physiology of muscle fibers, and age-related muscle mass loss, and is associated with loss of strength, increased frailty, and increased risk for fractures and falls. Treatment options are suboptimal and consist of exercise and nutrition as the cornerstone of therapy. Current treatment principles involve identification and modification of risk factors to prevent the disease, but these efforts are of limited value to the elderly individuals currently affected by sarcopenia...
August 17, 2017: Gerontology
https://www.readbyqxmd.com/read/28812967/tanshinone-induced-ers-suppresses-igfii-activation-to-alleviate-ang-ii-mediated-cardiac-hypertrophy
#4
Ya-Fang Chen, Nien-Hung Lee, Pei-Ying Pai, Li-Chin Chung, Chia-Yao Shen, Peramaiyan Rajendran, Yu-Feng Chen, Ray-Jade Chen, Vijaya Padma Viswanadha, Wei-Wen Kuo, Chih-Yang Huang
Cardiomyopathy involves changes in myocardial ultrastructure and cardiac hypertrophy. Angiotensin II (AngII) has previously been shown to stimulate the expression of IGF-2 and IGF-2R in H9c2 cardiomyoblasts and increase of blood pressure, and cardiac hypertrophy. Estrogen receptors (ERs) exert protective effects, such as anti-hypertrophy in cadiomyocytes. Tanshinone IIA (TSN), a main active ingredient from a Chinese medical herb, Salvia miltiorrhiza Bunge (Danshen), was shown to protect cardiomyocytes hypertrophy by different stress signals...
October 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28810619/microrna-503-suppresses-cell-proliferation-and-invasion-in-osteosarcoma-via-targeting-insulin-like-growth-factor-1-receptor
#5
Zili Wang, Chenhuang Zheng, Kunqi Jiang, Jinshen He, Xu Cao, Song Wu
MicroRNAs (miRs) are a class of small non-coding RNAs and have key roles in various cancer types. Recently, miR-503 has been reported to act as a tumor suppressor in osteosarcoma. However, the detailed mechanism of the regulatory role of miR-503 in osteosarcoma cell proliferation and invasion has largely remained elusive. The present study found that miR-503 was significantly downregulated in osteosarcoma tissues compared to that in matched adjacent non-tumorous tissues. In addition, the expression of miR-503 in osteosarcoma of T3-T4 stage was significantly lower when compared with that in T1-T2 stage samples...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28798204/imaging-igf-i-uptake-in-growth-plate-cartilage-using-in-vivo-multiphoton-microscopy
#6
Maria A Serrat, Gabriela Ion
Bones elongate through endochondral ossification in cartilaginous growth plates located at ends of primary long bones. Linear growth ensues from a cascade of biochemical signals initiated by actions of systemic and local regulators on growth plate chondrocytes. Although cellular processes are well defined, there is a fundamental gap in understanding how growth regulators are physically transported from surrounding blood vessels into and through dense, avascular cartilage matrix. Intravital imaging using in vivo multiphoton microscopy is one promising strategy to overcome this barrier by quantitatively tracking molecular delivery to cartilage from the vasculature in real time...
August 10, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28796787/the-quinic-acid-derivative-kz-41-prevents-glucose-induced-caspase-3-activation-in-retinal-endothelial-cells-through-an-igf-1-receptor-dependent-mechanism
#7
Hui He, Rebecca L Weir, Jordan J Toutounchian, Jayaprakash Pagadala, Jena J Steinle, Jerome Baudry, Duane D Miller, Charles R Yates
Retinal microaneurysms, an early disease manifestation of diabetic retinopathy, are associated with retinal endothelial cell (REC) death and macular edema. We previously demonstrated that a quinic acid (QA) analog, KZ-41, promoted REC survival by blunting stress-induced p38 MAPK activation. Herein, we sought to expand our understanding of the pro-survival signal transduction pathways actuated by KZ-41. Using human RECs exposed to high glucose (25 mM, 72 hours), we demonstrated that KZ-41 blocks caspase-3 activation by triggering phosphorylation of the PI3K regulatory subunit (p85; Tyr458) and its downstream target Akt (Ser473)...
2017: PloS One
https://www.readbyqxmd.com/read/28796250/p53-mediated-mir-18-repression-activates-hsf2-for-igf-iir-dependent-myocyte-hypertrophy-in-hypertension-induced-heart-failure
#8
Chih-Yang Huang, Pei-Ying Pai, Chia-Hua Kuo, Tsung-Jung Ho, Jing-Ying Lin, Ding-Yu Lin, Fu-Jen Tsai, V Vijaya Padma, Wei-Wen Kuo, Chih-Yang Huang
Hypertension-induced cardiac hypertrophy and attenuated cardiac function are the major characteristics of early stage heart failure. Cardiomyocyte death in pathological cardiac conditions is the primary cause of heart failure and mortality. Our previous studies found that heat shock factor 1 (HSF1) protected cardiomyocytes from death by suppressing the IGF-IIR signaling pathway, which is critical for hypertensive angiotensin II-induced cardiomyocyte apoptosis. However, the role of heat shock factor 2 (HSF2) in hypertension-induced cardiac hypertrophy is unknown...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28782619/differential-responses-of-mechanosensitive-osteocyte-proteins-in-forelimbs-and-hindlimbs-in-hindlimb-unloaded-rats
#9
Corinne E Metzger, Jessica E Brezicha, Jon P Elizondo, S Anand Narayanan, Harry A Hogan, Susan A Bloomfield
Osteocytes are believed to be the primary mechanosensors of bone tissue, signaling to osteoblasts and osteoclasts by releasing specific proteins. Sclerostin, interleukin-6 (IL-6), and insulin-like growth factor-I (IGF-I) are osteocyte proteins that signal to osteoblasts. This study's goals are to determine if osteocyte protein response to mechanical unloading is restricted to the unloaded bone using the hindlimb unloading (HU) rodent model. We also examined tumor necrosis factor-α (TNF-α) due to its interactions with all three osteocyte proteins...
August 3, 2017: Bone
https://www.readbyqxmd.com/read/28771323/synthetic-advances-in-insulin-like-peptides-enable-novel-bioactivity
#10
Fa Liu, Pengyun Li, Vasily Gelfanov, John Mayer, Richard DiMarchi
Insulin is a miraculous hormone that has served a seminal role in the treatment of insulin-dependent diabetes for nearly a century. Insulin resides within in a superfamily of structurally related peptides that are distinguished by three invariant disulfide bonds that anchor the three-dimensional conformation of the hormone. The additional family members include the insulin-like growth factors (IGF) and the relaxin-related set of peptides that includes the so-called insulin-like peptides. Advances in peptide chemistry and rDNA-based synthesis have enabled the preparation of multiple insulin analogues...
August 3, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28770685/insulin-igf-signaling-and-life-history-traits-in-response-to-food-availability-and-perceived-density-in-the-cnidarian-hydra-vulgaris
#11
Flóra Sebestyén, Szilárd Póliska, Rita Rácz, Judit Bereczki, Kinga Lénárt, Zoltán Barta, Ádám Z Lendvai, Jácint Tökölyi
Insulin/insulin-like growth factor signaling (IIS) is thought to be a central mediator of life history traits, but the generality of its role is not clear. Here, we investigated mRNA expression levels of three insulin-like peptide genes, the insulin-like receptor htk7, as well as several antioxidant genes, and the heat-shock protein hsp70 in the freshwater cnidarian Hydra vulgaris. Hydra polyps were exposed to a combination of different levels of food and perceived population density to manipulate life history traits (asexual reproduction and oxidative stress tolerance)...
August 2017: Zoological Science
https://www.readbyqxmd.com/read/28768911/a-ccr2-myeloid-cell-niche-required-for-pancreatic-%C3%AE-cell-growth
#12
Kristin Mussar, Stephanie Pardike, Tobias M Hohl, Gary Hardiman, Vincenzo Cirulli, Laura Crisa
Organ-specific patterns of myeloid cells may contribute tissue-specific growth and/or regenerative potentials. The perinatal stage of pancreas development marks a time characterized by maximal proliferation of pancreatic islets, ensuring the maintenance of glucose homeostasis throughout life. Ontogenically distinct CX3CR1+ and CCR2+ macrophage populations have been reported in the adult pancreas, but their functional contribution to islet cell growth at birth remains unknown. Here, we uncovered a temporally restricted requirement for CCR2+ myeloid cells in the perinatal proliferation of the endocrine pancreatic epithelium...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28768896/the-effects-of-graded-levels-of-calorie-restriction-xi-evaluation-of-the-main-hypotheses-underpinning-the-life-extension-effects-of-cr-using-the-hepatic-transcriptome
#13
Davina Derous, Sharon E Mitchell, Lu Wang, Cara L Green, Yingchun Wang, Luonan Chen, Jing-Dong J Han, Daniel E L Promislow, David Lusseau, Alex Douglas, John R Speakman
Calorie restriction (CR) may extend longevity by modulating the mechanisms involved in aging. Different hypotheses have been proposed for its main mode of action. We quantified hepatic transcripts of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months, and evaluated the responses relative to these various hypotheses. Of the four main signaling pathways implied to be linked to the impact of CR on lifespan (insulin/insulin like growth factor 1 (IGF-1), nuclear factor-kappa beta (NF-ĸB), mechanistic target of rapamycin (mTOR) and sirtuins (SIRTs)), all the pathways except SIRT were altered in a manner consistent with increased lifespan...
July 31, 2017: Aging
https://www.readbyqxmd.com/read/28758175/next-generation-sequencing-of-progressive-colorectal-liver-metastases-after-portal-vein-embolization
#14
Eve Simoneau, Jarred Chicoine, Sarita Negi, Ayat Salman, Anthoula Lazaris, Mazen Hassanain, Nicole Beauchemin, Stephanie Petrillo, David Valenti, Ramila Amre, Peter Metrakos
Portal vein embolization (PVE) can be required to stimulate liver regeneration before hepatectomy for colorectal liver metastasis (CRCLM), however PVE may also trigger CRCLM progression in patients initially exhibiting chemotherapy response. Using RNA-seq, we aimed to determine the molecular networks involved in metastatic progression in this context. A prospective study including all CRCLM patients undergoing PVE prior to hepatectomy was conducted. Paired biopsies of metastatic lesions were obtained prior to and after PVE and total RNA was isolated and used to prepare Illumina rRNA-depleted TruSeq stranded cDNA libraries for HiSeq 100 bp paired-end sequencing...
July 31, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28753565/enhanced-response-of-melanoma-cells-to-mek-inhibitors-following-unbiased-igf-1r-down-regulation
#15
Naida Suleymanova, Caitrin Crudden, Claire Worrall, Anica Dricu, Ada Girnita, Leonard Girnita
Due to its ability to compensate for signals lost following therapeutic MAPK-inhibition, insulin-like growth factor type 1 receptor (IGF-1R) co-targeting is a rational approach for melanoma treatment. However IGF-1R conformational changes associated with its inhibition can preferentially activate MAPK-pathway in a kinase-independent manner, through a process known as biased signaling. We explored the impact of biased IGF-1R signaling, on response to MAPK inhibition in a panel of skin melanoma cell lines with differing MAPK and p53 mutation statuses...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28747084/mir-615-5p-depresses-natural-killer-cells-cytotoxicity-through-repressing-igf-1r-in-hepatocellular-carcinoma-patients
#16
Mai Atef Rahmoon, Rana Ahmed Youness, Asmaa Ibrahim Gomaa, Mohamed Tarif Hamza, Imam Waked, Hend Mohamed El Tayebi, Ahmed Ihab Abdelaziz
miR-615-5p was characterized by our group as a tumour suppressor. IGF-1 R activates a downstream signalling pathway, well characterized in liver cells, however, its role in immunity especially Natural Killer cells (NKs) remains vague. This study aimed at investigating the regulatory role of miR-615-5p on IGF signalling and its impact on NKs cytotoxicity in HCC. Our results showed an upregulation in miR-615-5p and IGF-1 R in NKs of 130 HCC patients compared to 35 controls. Forcing the expression of miR-615-5p, repressed IGF-IR, attenuated NKs cytotoxicity, decreased CD56(dim), increased CD56(bright) NK subsets and reduced the cytotoxic markers NKG2D, TNF-α and perforins...
July 27, 2017: Growth Factors
https://www.readbyqxmd.com/read/28744224/downregulated-translation-initiation-signaling-predisposes-low-birth-weight-neonatal-pigs-to-slower-rates-of-muscle-protein-synthesis
#17
Ying Chen, Sydney R McCauley, Sally E Johnson, Robert P Rhoads, Samer W El-Kadi
Low-birth-weight (LBWT) neonates experience restricted muscle growth in their perinatal life. Our aim was to investigate the mechanisms that contribute to slower skeletal muscle growth of LBWT neonatal pigs. Twenty-four 1-day old male LBWT (816 ± 55 g) and normal-birth-weight (NBWT; 1,642 ± 55 g) littermates (n = 12) were euthanized to collect blood and longissimus dorsi (LD) muscle subsamples. Plasma glucose, insulin, and insulin-like growth factor-I (IGF-I) were lower in LBWT compared with NBWT pigs. Muscle IGF-I mRNA expression were lower in LBWT than NBWT pigs...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28743112/microrna-302b-3p-suppresses-cell-proliferation-through-akt-pathway-by-targeting-igf-1r-in-human-gastric-cancer
#18
Bo Guo, Zhenghao Zhao, Zhen Wang, Qian Li, Xiaofei Wang, Wenjing Wang, Tusheng Song, Che Huang
BACKGROUND/AIMS: MiR-302b is a major microRNA found in human embryonic stem cells and induced pluripotent stem cells. However, its function in gastric cancer progression remains unclear. METHODS: Quantitative reverse transcription-PCR was performed to detect the expression levels of miR-302b-3p in gastric cancer tissues. MTT, colony formation, and flow cytometer analyses were conducted to explore the function of miR-302b-3p in MKN-45/SGC-7901 cells. A dual-luciferase reporter was used to validate the bioinformatics-predicted target gene of miR-302b-3p...
July 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28741071/a-multicenter-observational-study-of-lanreotide-depot-autogel-lan-in-patients-with-acromegaly-in-the-united-states-2-year-experience-from-the-soda-registry
#19
Roberto Salvatori, Murray B Gordon, Whitney W Woodmansee, Adriana G Ioachimescu, Don W Carver, Beloo Mirakhur, David Cox, Mark E Molitch
PURPOSE: This analysis evaluates the 2-year effectiveness and safety of lanreotide depot/autogel (LAN), as well as treatment convenience and acromegaly symptom relief, from the Somatuline(®) Depot for Acromegaly (SODA) registry, a post-marketing, open-label, observational, multicenter, United States registry study. METHODS: Patients with acromegaly treated with LAN were eligible for enrollment. Demographics, LAN dose, extended dosing interval (EDI) (interval of injections ≥42 days), insulin-like growth factor 1 (IGF-1), growth hormone (GH), glycated hemoglobin, adverse events (AEs), injection convenience, and symptom data were collected...
July 24, 2017: Pituitary
https://www.readbyqxmd.com/read/28740570/quercetin-reverses-rat-liver-preneoplastic-lesions-induced-by-chemical-carcinogenesis
#20
Gabriela Carrasco-Torres, Hugo Christian Monroy-Ramírez, Arturo Axayacatl Martínez-Guerra, Rafael Baltiérrez-Hoyos, María de Los Ángeles Romero-Tlalolini, Saúl Villa-Treviño, Xariss Sánchez-Chino, Verónica Rocío Vásquez-Garzón
Quercetin is a flavonoid widely studied as a chemopreventive agent in different types of cancer. Previously, we reported that quercetin has a chemopreventive effect on the liver-induced preneoplastic lesions in rats. Here, we evaluated if quercetin was able not only to prevent but also to reverse rat liver preneoplastic lesions. We used the modified resistant hepatocyte model (MRHM) to evaluate this possibility. Treatment with quercetin was used 15 days after the induction of preneoplastic lesions. We found that quercetin reverses the number of preneoplastic lesions and their areas...
2017: Oxidative Medicine and Cellular Longevity
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