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https://www.readbyqxmd.com/read/28328298/the-synthetic-progestin-gestodene-affects-functional-biomarkers-in-neonatal-rat-osteoblasts-through-an-estrogen-receptor-related-mechanism-of-action
#1
Juana Enríquez, Gustavo García, Bertha Herrero, Fernando Larrea
BACKGROUND: Clinical studies have shown that gestodene (GDN), a potent third-generation synthetic progestin, affects bone resorption. However, its mode of action in bone cells is not fully understood. The aim of this study was to establish whether GDN affects bone directly or through its bioconversion to other metabolites with different biological activities. METHODS: In this study, we investigated the effects of GDN and its A-ring reduced metabolites on proliferation, differentiation, and mineralization of calvarial osteoblasts isolated from neonatal rat and their capacity to displace [(3)H]-E2 at ER binding sites...
March 22, 2017: Endocrine Research
https://www.readbyqxmd.com/read/28322974/current-modalities-in-cancer-immunotherapy-immunomodulatory-antibodies-cars-and-vaccines
#2
REVIEW
Jason Lohmueller, Olivera J Finn
Successes of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cell therapy in curing patients with otherwise lethal cancers have validated immunotherapy as a treatment for cancer and have inspired excitement for its broader potential. Most promising is the ability of each approach to eliminate bulky and advanced-stage cancers and to achieve durable cures. Despite this success, to date only a subset of cancer patients and a limited number of cancer types respond to these therapies. A major goal now is to expand the types of cancer and number of patients who can be successfully treated...
March 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28322764/cloning-expression-and-functional-characterization-on-vitellogenesis-of-estrogen-receptors-in-scatophagus-argus
#3
Xue-Fan Cui, Yuan Zhao, Hua-Pu Chen, Si-Ping Deng, Dong-Neng Jiang, Tian-Li Wu, Chun-Hua Zhu, Guang-Li Li
Estrogen receptors (Er) play a critical role in vitellogenesis. Three ers (erα, erβ1 and erβ2) and vitellogenins (vtg-A, vtg-B and vtg-C) subtypes were isolated in various fish species, while the contribution of each Er to the regulation of vtgs expression was not analyzed in detail. Here, erα, erβ1 and erβ2 were cloned and all were found to be expressed in female liver in Scatophagus argus. During proteic vitellogenesis stage, erα was simultaneously up-regulated, while erβ1 and erβ2 were not, with three vtgs in female liver...
March 18, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28320163/inhibition-of-17-beta-estradiol-on-neuronal-excitability-via-enhancing-girk1-mediated-inwardly-rectifying-potassium-currents-and-girk1-expression
#4
Yuwen Zhang, Yian Huang, Guoxiang Wang, Xin Wang, Yun Wang
BACKGROUND: Catamenial epilepsy is a common central nervous system disease in female, which is influenced by the 17-β-estradiol (estrogen) level during the menstrual cycle. Low level (<0.05ng/ml) of estrogen normally accompanies with the perimenstrual classification of catamenial epilepsy, however, without clear mechanism. In previous studies, estrogen has been demonstrated to possess widely regulatory effects on potassium channels. Here, the effect of 17-β-estradiol on modulating inwardly rectifying K(+) (Kir) currents was investigated in cultured hippocampal neurons...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28303768/diffuse-edema-suggestive-of-cytokine-release-syndrome-in-a-metastatic-lung-carcinoma-patient-treated-with-pembrolizumab
#5
Elie El Rassy, Tarek Assi, Jamale Rizkallah, Joseph Kattan
Immune checkpoint inhibitors (ICIs) are actually being indicated more commonly in the management of chemoresistant cancer patients in view of their favorable toxicity profile in comparison to cytotoxic chemotherapy. In this paper, we report, to our knowledge, the first case suggestive of cytokine release syndrome secondary to pembrolizumab in a patient with metastatic lung squamous cell carcinoma. In view of the quick approvals of ICI and the absence of sufficient knowledge of the corresponding toxicity profile, the occurrence of any clinical or biological sign or symptom in patients receiving ICI requires further investigation...
March 2017: Immunotherapy
https://www.readbyqxmd.com/read/28290507/inhibitory-interneuron-circuits-at-cortical-and-spinal-levels-are-associated-with-individual-differences-in-corticomuscular-coherence-during-isometric-voluntary-contraction
#6
Ryosuke Matsuya, Junichi Ushiyama, Junichi Ushiba
Corticomuscular coherence (CMC) is an oscillatory synchronization of 15-35 Hz (β-band) between electroencephalogram (EEG) of the sensorimotor cortex and electromyogram of contracting muscles. Although we reported that the magnitude of CMC varies among individuals, the physiological mechanisms underlying this variation are still unclear. Here, we aimed to investigate the associations between CMC and intracortical inhibition (ICI) in the primary motor cortex (M1)/recurrent inhibition (RI) in the spinal cord, which probably affect oscillatory neural activities...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28284859/molecular-mechanisms-of-3-3-4-4-5-pentachlorobiphenyl-induced-epithelial-mesenchymal-transition-in-human-hepatocellular-carcinoma-cells
#7
Li Song, Linlin Guo, Zhuoyu Li
Polychlorinated biphenyls (PCBs) are classic persistent organic pollutants (POPs). Many studies have found a positive association between the progression of hepatocellular carcinoma (HCC) and PCBs exposure. However, the influence of PCBs on epithelial-mesenchymal transition (EMT) of HCC remains to be unclear. In this study, we explored the effect of PCB126 on EMT in HCC cells and its underlying mechanisms. The data showed that PCB126, exposing both Bel-7402 and SMMC-7721 cells for 48h, promoted EMT that was demonstrated by E-cadherin repression, up-regulation of N-cadherin and vimentin, and morphological alteration...
March 8, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28284154/contribution-of-g-protein-coupled-estrogen-receptor-1-gper-to-17%C3%AE-estradiol-induced-developmental-toxicity-in-zebrafish
#8
Graciel Diamante, Norma Menjivar-Cervantes, Man Sin Leung, David C Volz, Daniel Schlenk
Exposure to 17β-estradiol (E2) influences the regulation of multiple signaling pathways, and E2-mediated disruption of signaling events during early development can lead to malformations such as cardiac defects. In this study, we investigated the potential role of the G-protein estrogen receptor 1 (GPER) in E2-induced developmental toxicity. Zebrafish embryos were exposed to E2 from 2h post fertilization (hpf) to 76 hpf with subsequent transcriptional measurements of heart and neural crest derivatives expressed 2 (hand2), leucine rich repeat containing 10 (lrrc10), and gper at 12, 28 and 76 hpf...
March 2, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28283550/the-effects-of-%C3%AE-adrenergic-receptor-drugs-on-embryonic-ventricular-cell-proliferation-and-differentiation-and-their-impact-on-donor-cell-transplantation
#9
Tiam Feridooni, Adam Hotchkiss, Mark Baguma-Nibasheka, Feixiong Zhang, Brittney Allen, Sarita Chinni, Kishore B S Pasumarthi
The beta-adrenergic receptors (β-ARs) and catecholamines are present in rodents as early as embryonic day 10.5 (E10.5). However, it is not known whether β-AR signaling plays any role in proliferation and differentiation of ventricular cells in the embryonic heart. Here, we characterized the expression profiles of β-AR subtypes and established dose response curves for a nonselective β-AR agonist isoproterenol (ISO) in the developing mouse ventricular cells. Further, we investigated the effects of ISO on cell cycle activity and differentiation of cultured E11...
March 10, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28283388/psoralidin-a-prenylated-coumestan-as-a-novel-anti-osteoporosis-candidate-to-enhance-bone-formation-of-osteoblasts-and-decrease-bone-resorption-of-osteoclasts
#10
Yuankun Zhai, Yingying Li, Yanping Wang, Jiawei Cui, Kun Feng, Xijian Kong, Li Chen
Traditional Chinese medicines (TCM) have been proven to prevent osteoporosis, but their clinical applications are not widely recognized due to their complicated ingredients. Psoralidin, a prenylated coumestan, has been reported to prevent bone loss of ovariectomized rats, but detailed mechanisms are still not clear. In current study, we found that both psoralidin and coumestrol promoted osteoblast proliferation and differentiation, as evidenced by improvements in cell proliferation and alkaline phosphatase activity; increased formation of ALP colonies and calcified nodules; enhanced secretion of collagen-I, BMP-2, osteocalcin and osteopontin; and stimulation of the expression of IGF-1, β-catenin, Runx-2, Osterix, and OPG, as well as the mRNA ratio of OPG/RANKL, while significantly decreasing the expression of RANKL...
March 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28255267/17beta-estradiol-attenuates-tnf-%C3%AE-induced-premature-senescence-of-nucleus-pulposus-cells-through-regulating-the-ros-nf-%C3%AE%C2%BAb-pathway
#11
Pei Li, Yibo Gan, Yuan Xu, Liyuan Wang, Bin Ouyang, Chengmin Zhang, Lei Luo, Chen Zhao, Qiang Zhou
BACKGROUND: Accelerated cellular senescence within the nucleus pulposus (NP) region is a common feature of disc degeneration. Our previous work indicated that TNF-α promoted NP cell senescence. Although the intervertebral disc has been reported to be an estrogen-sensitive tissue, it is unclear whether estrogen can inhibit premature senescence of NP cells. OBJECTIVE: To investigate whether 17beta-estradiol (E2) can attenuate TNF-α-induced premature senescence of NP cells and the potential mechanism behind this regulatory process...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28254356/reviewing-the-management-of-obstructive-left-colon-cancer-assessing-the-feasibility-of-the-one-stage-resection-and-anastomosis-after-intraoperative-colonic-irrigation
#12
Gavish Kumar Awotar, Guoxin Guan, Wei Sun, Hongliang Yu, Ming Zhu, Xinye Cui, Jie Liu, Jiaxi Chen, Baoshun Yang, Jianyu Lin, Zeyong Deng, Jianwei Luo, Chen Wang, Osman Abdifatah Nur, Panjak Dhiman, Pixu Liu, Fuwen Luo
BACKGROUND: The management of obstructive left colon cancer (OLCC) remains debatable with the single-stage procedure of primary colonic anastomosis after cancer resection and on-table intracolonic lavage now being supported. PATIENTS AND METHODS: Patients with acute OLCC who were admitted between January 2008 and January 2015 were distributed into 5 different groups. Group ICI underwent emergency laparotomy for primary anastomosis following colonic resection and intraoperative colonic lavage; Group HP underwent emergency Hartmann's Procedure; Group CON consisted of patients treated by conservative management with subsequent elective open cancer resection; Group COL were colostomy patients; and Group INT consisted of patients who had interventional radiology followed by open elective colon cancer resection...
January 18, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28253279/demineralized-bone-matrix-used-for-direct-pulp-capping-in-rats
#13
Qian Liu, Yanhong Ma, Junlan Wang, Xuefang Zhu, Yanjing Yang, Yufeng Mei
OBJECTIVES: To evaluate the wound healing process following direct pulp capping with demineralized bone matrix (DBM) and calcium hydroxide (Ca(OH)2). METHODS: Fifty 8-weeks-old SPF Wistar male rats were divided into two groups: one was the DBM treated group, and the other was the Ca(OH)2 treated group. Pulpotomy was performed on the maxillary first molar of one side of each rat, and the another side was left as the blank control. Rats were sacrificed after each observation period (1, 3, 7, 14 and 28 days) and specimen slices were made...
2017: PloS One
https://www.readbyqxmd.com/read/28246107/comprehensive-meta-analysis-of-key-immune-related-adverse-events-from-ctla-4-and-pd-1-pd-l1-inhibitors-in-cancer-patients
#14
Guillermo De Velasco, Youjin Je, Dominick Bossé, Mark M Awad, Patrick A Ott, Raphael B Moreira, Fabio A B Schutz, Joaquim Bellmunt, Guru Sonpavde, F Stephen Hodi, Toni K Choueiri
Immune-related adverse events (irAEs) have been described with immune checkpoint inhibitors (ICIs), but the incidence and relative risk (RR) of irAEs associated with these drugs remains unclear. We selected five key irAEs from treatments with approved cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors (ipilimumab, nivolumab or pembrolizumab, and atezolizumab, respectively) to better characterize their safety profile. We performed a meta-analysis of randomized phase II/III immunotherapy trials, with non-ICI control arms, conducted between 1996 and 2016...
February 28, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28244646/17%C3%AE-oestradiol-promotes-differentiation-of-human-embryonic-stem-cells-into-dopamine-neurons-via-cross-talk-between-insulin-like-growth-factors-1-and-oestrogen-receptor-%C3%AE
#15
Hong Li, Chenyue Ding, Zhi-Liang Ding, Mingfa Ling, Ting Wang, Wei Wang, Boxian Huang
Human embryonic stem cells (hESCs) can self-renew and differentiate into all cell lineages. E2 is known to exhibit positive effects on embryo development. Although the importance of E2 in many physiological processes has been reported, to date few researchers have investigated the effects of E2 on hESCs differentiation. We studied the effects of E2 on dopamine (DA) neuron induction of hESCs and its related signalling pathways using the three-stage protocol. In our study, 0.1 μM E2 were applied to hESCs-derived human embryoid bodies (hEBs) and effects of E2 on neural cells differentiation were investigated...
February 28, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28240737/fatty-acid-synthase-regulates-estrogen-receptor-%C3%AE-signaling-in-breast-cancer-cells
#16
J A Menendez, R Lupu
Fatty acid synthase (FASN), the key enzyme for endogenous synthesis of fatty acids, is overexpressed and hyperactivated in a biologically aggressive subset of sex steroid-related tumors, including breast carcinomas. Using pharmacological and genetic approaches, we assessed the molecular relationship between FASN signaling and estrogen receptor alpha (ERα) signaling in breast cancer. The small compound C75, a synthetic slow-binding inhibitor of FASN activity, induced a dramatic augmentation of estradiol (E2)-stimulated, ERα-driven transcription...
February 27, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28228726/current-diagnosis-and-management-of-immune-related-adverse-events-iraes-induced-by-immune-checkpoint-inhibitor-therapy
#17
REVIEW
Vivek Kumar, Neha Chaudhary, Mohit Garg, Charalampos S Floudas, Parita Soni, Abhinav B Chandra
The indications of immune checkpoint inhibitors (ICIs) are set to rise further with the approval of newer agents like tremelimumab and atezolimumab for use in patients with advanced stage mesothelioma and urothelial carcinoma respectively. More frequent use of ICIs has improved our understanding of their unique side effects, which are known as immune-related adverse events (irAEs). The spectrum of irAEs has expanded beyond more common manifestations such as dermatological, gastrointestinal and endocrine effects to rarer presentations involving nervous, hematopoietic and urinary systems...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28223073/immunotherapy-comes-of-age-immune-aging-checkpoint-inhibitors
#18
REVIEW
Rawad Elias, Theodoros Karantanos, Elizabeth Sira, Kevan L Hartshorn
Immune checkpoint inhibitors (ICIs) are based on the understanding that there are multilayered checks and balances which can be manipulated to unleash already existing, but paralyzed, immune responses to cancer. These agents are safer and more efficacious than classic cytotoxic drugs making them a very attractive therapeutic option, especially in older adults. Current available data do not suggest significant age-associated differences in the clinical profile of ICIs. It must be noted, however, that there is still relatively little information on the use of ICIs in adults over 75years of age and aging is associated with a decline in the immune system or "immunosenescence" which theoretically can reduce the efficacy of these immune based therapies...
February 17, 2017: Journal of Geriatric Oncology
https://www.readbyqxmd.com/read/28219710/unique-effect-of-4-hydroxyestradiol-and-its-methylation-metabolites-on-lipid-and-cholesterol-profiles-in-ovariectomized-female-rats
#19
Pan Wang, Bao-Ting Zhu
Animal studies have shown that endogenous estrogens such as 17β-estradiol (E2) can modulate lipid profiles in vivo, and this effect is generally thought to be mediated by the estrogen receptors (ERs). The present study sought to test a hypothesis that some of the endogenous estrogen metabolites that have very weak estrogenic activity may exert some of their modulating effects on lipid metabolism in an ER-independent manner. Using ovariectomized female rats as an in vivo model, we found that 4-hydroxyestradiol (4-OH-E2) has a markedly stronger effect in reducing the adipocyte size and serum cholesterol level in rats compared to E2, despite the weaker estrogenic activity of 4-OH-E2...
April 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28215489/the-role-of-estrogen-receptor-subtypes-for-induction-of-delayed-effects-on-the-estrous-cycle-and-female-reproductive-organs-in-rats
#20
Miwa Takahashi, Ryohei Ichimura, Kaoru Inoue, Tomomi Morikawa, Kazunori Kuwata, Gen Watanabe, Midori Yoshida
It has been reported that neonatal exposure to estrogens at relatively low doses can induce early onset anovulation as a delayed effect in female rats. Dysfunction of kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) was proposed to be a trigger for this effect. To determine the roles of estrogen receptor (ER) subtypes in the induction of delayed effects, we conducted a series of experiments using Donryu rats to examine whether neonatal injection of an ERα agonist (PPT), an ERβ agonist (DPN) or an ERα antagonist (ICI) could induce delayed effects...
February 16, 2017: Reproductive Biology
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