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Multifunctional Applications of Engineered Extracellular Vesicles in the Treatment of Cancer.
Abstract Extracellular vesicles (EVs) are key players of intercellular communication in the physiological and pathological setting. In cancer, EVs mediate complex signaling mechanisms between cancer cells and the tumor microenvironment (TME), and can influence tumor progression and the response to existing therapies. Importantly, EVs can be loaded with therapeutic agents and modified to display tumor-targeting molecules. In the field of nanomedicine, EVs have been engineered to serve as therapeutic delivery vehicles for several anticancer agents, including antibodies, chemotherapy, compounds, CRISPR/Cas9 (clustere...
Source: Endocrinology - February 12, 2021 Category: Endocrinology Authors: Kugeratski FG, McAndrews KM, Kalluri R Tags: Endocrinology Source Type: research

Recombinant Thrombomodulin Attenuates Preeclamptic Symptoms by Inhibiting High Mobility Group Box 1 in Mice.
Abstract Preeclampsia (PE) is a common gestational complication that involves systemic endothelial dysfunction and inflammatory responses primarily due to placental damage. Recombinant thrombomodulin (rTM), a novel anti-coagulant clinically used for disseminated intravascular coagulation, is reported to have a unique anti-inflammatory endothelial repair function by inhibiting proinflammatory mediator high mobility group box 1 (HMGB1). Despite the severe patient outcomes, there are currently no effective therapeutic to treat PE. Here, we verified the efficacy of rTM as a novel therapeutic agent for PE using a murin...
Source: Endocrinology - January 6, 2021 Category: Endocrinology Authors: Oda H, Nagamatsu T, Schust DJ, Cabral H, Miyazaki T, Iriyama T, Kawana K, Osuga Y, Fujii T Tags: Endocrinology Source Type: research

GPR120 regulates pancreatic polypeptide secretion from male mouse islets via PLC-mediated calcium mobilization.
In this study, GPR120-IRES-EGFP knockin (KI) mouse was generated to identify GPR120-expressing cells with enhance green fluorescence proteins (EGFP). EGFP-positive cells collected from the KI mouse islets by flow cytometry had significantly higher expression of pancreatic polypeptide (PP) evidenced by RT-qPCR. Single cell RT-PCR and immunocytochemical double staining also demonstrated the co-expression of GPR120 with PP in mouse islets. GPR120 specific agonist, TUG-891, significantly increased plasma PP levels in mice. TUG-891 significantly increased PP levels in islet medium in vitro, which was markedly attenuated by GPR1...
Source: Endocrinology - September 1, 2020 Category: Endocrinology Authors: Zhao YF, Li XC, Liang XY, Zhao YY, Xie R, Zhang LJ, Zhang XC, Chen C Tags: Endocrinology Source Type: research

The autophagy gene Atg16L1 is necessary for endometrial decidualization.
Abstract Uterine receptivity is critical for establishing and maintaining pregnancy. For the endometrium to become receptive, stromal cells must differentiate into decidual cells capable of secreting factors necessary for embryo survival and placental development. Although there are multiple reports of autophagy induction correlated with endometrial stromal cell decidualization, the role of autophagy in decidualization remained elusive. To determine the role of autophagy in decidualization, we utilized two genetic models carrying mutations to the autophagy gene Atg16L1. Although the hypomorphic Atg16L1 mouse was f...
Source: Endocrinology - December 25, 2019 Category: Endocrinology Authors: Oestreich AK, Chadchan SB, Popli P, Medvedeva A, Rowen MN, Stephens CS, Xu R, Lydon JP, Demayo FJ, Jungheim ES, Moley KH, Kommagani R Tags: Endocrinology Source Type: research

PKC-delta mediates mineralocorticoid receptor activation by angiotensin II to modulate smooth muscle cell function.
Abstract Angiotensin II (AngII) and the mineralocorticoid receptor(MR) ligand aldosterone, both contribute to cardiovascular disorders, including hypertension and adverse vascular remodeling.We previously demonstrated that AngII activates MR-mediated gene transcription in human vascular smooth muscle cells(SMC) yet the mechanism and the impact on SMC function are unknown.Using a MR responsive element-driven transcriptional reporter assay, we confirm that AngII induces MR transcriptional activity in multiple vascular SMC and endothelial cells, but not in Cos1 nor HEK293 cells.AngII activation of MR was blocked by t...
Source: Endocrinology - August 1, 2019 Category: Endocrinology Authors: Lu Q, Davel AP, McGraw AP, Rao SP, Newfell BG, Jaffe IZ Tags: Endocrinology Source Type: research

Dihydrotestosterone increases cytotoxic activity of macrophages on prostate cancer cells via TRAIL.
Abstract Although androgen depravation therapy (ADT) and immunotherapy are potential treatment options in men with metastatic prostate cancer (CaP), androgen has conventionally been proposed to be a suppressor of the immune response. However, we herein report that dihydrotestosterone (DHT) activates macrophages. When the murine macrophage cell line (RAW 264.7), human monocyte (THP-1), and human peripheral blood monocytes were cultured with androgen-resistant CaP cell lines, DHT increased cytotoxicity of macrophages in a concentration-dependent manner. Further studies revealed that DHT induced M1 polarization and i...
Source: Endocrinology - June 10, 2019 Category: Endocrinology Authors: Lee GT, Kim JH, Kwon SJ, Stein MN, Hong JH, Nagaya N, Billakanti S, Kim MM, Kim WJ, Kim IY Tags: Endocrinology Source Type: research

Serpina3n, dominantly expressed in female osteoblasts, suppresses the phenotypes of differentiated osteoblasts in mice.
In conclusion, we first found Serpina3n as the most female osteoblast-dominant gene. Serpina3n exerts a suppression of the osteoblast phenotypes such as Col1a1 expression and ALP activity in differentiated osteoblasts, which might partly explain sex differences of the osteoblast phenotypes in mice. PMID: 30304388 [PubMed - as supplied by publisher]
Source: Endocrinology - October 9, 2018 Category: Endocrinology Authors: Ishida M, Kawao N, Okada K, Tatsumi K, Sakai K, Nishio K, Kaji H Tags: Endocrinology Source Type: research

Mechanism of Telapristone acetate (CDB4124) on Progesterone receptor action in breast cancer cells.
In conclusion, TPA decreases PR occupancy on chromatin, recruits co-regulators such as TRPS1 to the PR complex thereby regulates PR target gene expression and associated cellular responses. PMID: 30203004 [PubMed - as supplied by publisher]
Source: Endocrinology - September 6, 2018 Category: Endocrinology Authors: Davaadelger B, Murphy AR, Clare SE, Lee O, Khan SA, Kim JJ Tags: Endocrinology Source Type: research

Alpha7 Nicotinic Acetylcholine Receptor Regulates the Function and Viability of Enteroendocrine L Cells In Vitro.
Abstract Enteroendocrine L cells secrete the incretin hormone glucagon-like peptide-1 (GLP-1) and they also express the α7 nicotinic acetylcholine receptor (α7nAChR) that might regulate GLP-1 secretion. Here, GTS-21, a selective α7nAChR agonist, was used to examine the impact of α7nAChR activation in L-cell lines, mouse intestinal primary cell cultures, and C57BL/6 mice. GTS-21 stimulated GLP-1 secretion in vitro and this effect was attenuated by an α7nAChR antagonist or by α7nAChR-specific siRNA. Under in vitro cell culture conditions of glucotoxicity, GTS-21 restored GLP-1 secretion and improved L-cell via...
Source: Endocrinology - July 9, 2018 Category: Endocrinology Authors: Wang D, Meng Q, Leech CA, Yepuri N, Zhang L, Holz GG, Wang C, Cooney RN Tags: Endocrinology Source Type: research

miR-122 Regulates LHR Expression in Rat Granulosa Cells by Targeting Insig1 mRNA.
We present evidence showing that mRNA and protein levels of Insig1 undergo a time-dependent increase following the treatment of rat granulosa cells with FSH, which leads to a decrease in LRBP levels. Furthermore, overexpression of miR-122 using an adenoviral vector (AdmiR-122) abolished FSH-induced increases in Insig1 mRNA and protein. We further confirmed the role of Insig1 by showing that inhibition of Insig1 using a specific siRNA (siInsig1) prior to FSH treatment resulted in the abrogation of LHR upregulation. Silencing of Insig1 also reversed FSH-mediated decreases in SREBP and LRBP activation. These results show that...
Source: Endocrinology - March 19, 2018 Category: Endocrinology Authors: Menon B, Guo X, Garcia N, Gulappa T, Menon KMJ Tags: Endocrinology Source Type: research

cGMP/PKG-I pathway-mediated GLUT1/4 regulation by NO (nitric oxide) in female rat granulosa cells.
The objective of the present study was to determine the cellular and molecular mechanism by which NO regulates GLUT expression and glucose uptake in granulosa cells. Our results indicated that NO increased GLUT1/GLUT4 expression and translocation in cells, as well as glucose uptake. These changes were accompanied by upregulation of cGMP level and PKG-I protein content. The results of siRNA analysis showed that knockdown of PKG-I significantly attenuated gene expression, translocation and glucose uptake. Moreover, the PKG-I inhibitor also blocked the above processes. Furthermore, NO induced CREB phosphorylation, and CREB si...
Source: Endocrinology - December 28, 2017 Category: Endocrinology Authors: Tian Y, Heng D, Xu K, Liu W, Weng X, Hu X, Zhang C Tags: Endocrinology Source Type: research

Identification of Estrogen-Related Receptor Alpha Agonists in the Tox21 Compound Library.
This study is the first comprehensive analysis in discovering potential endocrine disrupters which affect the ERRα signaling pathway. PMID: 29216352 [PubMed - as supplied by publisher]
Source: Endocrinology - December 4, 2017 Category: Endocrinology Authors: Lynch C, Zhao J, Huang R, Kanaya N, Bernal L, Hsieh JH, Auerbach SS, Witt KL, Merrick BA, Chen S, Teng CT, Xia M Tags: Endocrinology Source Type: research

Notch signaling regulates differentiation and steroidogenesis in female mouse ovarian granulosa cells.
Abstract The Notch pathway is a highly conserved juxtacrine signaling mechanism that is important for many cellular processes during development, including differentiation and proliferation. While Notch is important during ovarian follicle formation and early development, its functions during the gonadotropin-dependent stages of follicle development are largely unexplored. We observed positive regulation of Notch activity and expression of Notch ligands and receptors following activation of the LH-receptor in prepubertal mouse ovary. JAG1, the most abundantly expressed Notch ligand in mouse ovary, revealed a strik...
Source: Endocrinology - November 8, 2017 Category: Endocrinology Authors: Prasasya RD, Mayo KE Tags: Endocrinology Source Type: research

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