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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

Reduced expression of mismatch repair genes MSH6/MSH2 directly promotes pituitary tumor growth via the ATR-Chk1 pathway.
Conclusion: Reduction of MSH6 and MSH2 expression at the mRNA and protein levels could be involved in direct PA proliferation by promoting cell-cycle progression or decreasing the rate of apoptosis through interference with the function of the ATR-Chk1 pathway. PMID: 29342268 [PubMed - as supplied by publisher]
Source: The Journal of Clinical Endocrinology and Metabolism - January 12, 2018 Category: Endocrinology Authors: Uraki S, Ariyasu H, Doi A, Kawai S, Takeshima K, Morita S, Fukai J, Fujita K, Furuta H, Nishi M, Sugano K, Inoshita N, Nakao N, Yamada S, Akamizu T Tags: J Clin Endocrinol Metab Source Type: research

miR-92a Corrects CD34+ Cell Dysfunction in Diabetes by Modulating Core Circadian Genes Involved in Progenitor Differentiation
In this study, we examine expression of the clock genes Clock, Bmal, Per1, Per2, Cry1, and Cry2 in CD34+ cells of diabetic and nondiabetic origin and determine the small encoding RNA (miRNA) profile of these cells. The degree of diabetic retinopathy (DR) was assessed. As CD34+ cells acquired mature endothelial markers, they exhibit robust oscillations of clock genes. siRNA treatment of CD34+ cells revealed Per2 as the only clock gene necessary to maintain the undifferentiated state of CD34+ cells. Twenty-five miRNAs targeting clock genes were identified. Three of the miRNAs (miR-18b, miR-16, and miR-34c) were found only in...
Source: Diabetes - November 24, 2015 Category: Endocrinology Authors: Bhatwadekar, A. D.; Yan, Y.; Stepps, V.; Hazra, S.; Korah, M.; Bartelmez, S.; Chaqour, B.; Grant, M. B. Tags: Complications Source Type: research

Tissue-type plasminogen activator deficiency delays bone repair: roles of osteoblastic proliferation and vascular endothelial growth factor
Further development in research of bone regeneration is necessary to meet the clinical demand for bone reconstruction. Recently, we reported that plasminogen is crucial for bone repair through enhancement of vessel formation. However, the details of the role of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) in the bone repair process still remain unknown. Herein, we examined the effects of plasminogen activators on bone repair after a femoral bone defect using tPA-deficient (tPA–/–) and uPA-deficient (uPA–/–) mice. Bone repair of the femur was delayed in tPA&n...
Source: AJP: Endocrinology and Metabolism - August 1, 2014 Category: Endocrinology Authors: Kawao, N., Tamura, Y., Okumoto, K., Yano, M., Okada, K., Matsuo, O., Kaji, H. Tags: Articles Source Type: research

Caveolin-1/PTRF upregulation constitutes a mechanism for mediating p53-induced cellular senescence: implications for evidence-based therapy of delayed wound healing in diabetes
A heightened state of oxidative stress and senescence of fibroblasts constitute potential therapeutic targets in nonhealing diabetic wounds. Here, we studied the underlying mechanism mediating diabetes-induced cellular senescence using in vitro cultured dermal fibroblasts and in vivo circular wounds. Our results demonstrated that the total antioxidant capacity and mRNA levels of thioredoxinreductase and glucose-6-phosphate dehydrogenase as well as the ratio of NADPH/NADP were decreased markedly in fibroblasts from patients with type 2 diabetes (DFs). Consistent with this shift in favor of excessive reactive oxygen species,...
Source: AJP: Endocrinology and Metabolism - October 15, 2013 Category: Endocrinology Authors: Bitar, M. S., Abdel-Halim, S. M., Al-Mulla, F. Tags: Articles Source Type: research