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Based on this finding, (R)-LMI was selected for pharmacological characterization. We have found that (R)-LMI is a CRF antagonist, inhibiting (1) the CRF-stimulated accumulation of cAMP in HEK 293 cells expressing the CRF1R, (2) the production of interleukins by adipocytes and (3) the proliferation rate of RAW 264.7 cells. (R)-LMI likely blocked agonist actions by interacting with the N-domain of CRF1R as suggested by data using a constitutively active chimera of CRF1R. We propose that (R)-LMI can be used as an optimal lead compound in the rational design of novel CRF antagonists.Creatine is an amino acid derivative synthesized from arginine, glycine and methionine. It serves as the substrate for the creatine kinase system, which is vital for maintaining ATP levels in tissues with high and fluctuating energy demand. There exists evidence that the creatine kinase system operates in both the endometrial and myometrial layers of the uterus. While use and regulation of this system in the uterus are not well understood, it is likely to be important given uterine tissues undergo phases of increased energy demand during certain stages of the female reproductive cycle, pregnancy, and parturition. This review discusses known adaptations of creatine metabolism in the uterus during the reproductive cycle (both estrous and menstrual), pregnancy and parturition, highlighting possible links to fertility and the existing knowledge gaps. Specifically, we discuss the adaptations and regulation of uterine creatine metabolite levels, cell creatine transport, de novo creatine synthesis, and creatine kinase expression in the various layers and cell types of the uterus. Finally, we discuss the effects of dietary creatine on uterine metabolism. In summary, there is growing evidence that creatine metabolism is up-regulated in uterine tissues during phases where energy demand is increased. While it remains unclear how important these adaptations are in the maintenance of healthy uterine function, furthering our understanding of uterine creatine metabolism may uncover strategies to combat poor embryo implantation and failure to conceive, as well as enhancing uterine contractile performance during labor.

Subarachnoid hemorrhage (SAH) is a devastating neurological injury, further complicated by few available methods to objectively predict outcomes. With the recent shift in focus to neuroinflammation as a potential cause of adverse outcomes following SAH, we investigated the inflammasome-derived enzyme, caspase-1, as a potential biomarker for poor functional outcome.

SAH patients were recruited from a regional stroke referral center. Cerebrospinal fluid (CSF) samples from 18 SAH subjects were collected via an external ventricular drain and obtained as close as possible to admission (within 72h). For control subjects, we collected CSF from 9 patients undergoing lumbar puncture with normal CSF. Caspase-1 activity was measured using commercially available luminescence assays. SAH subjects were categorized at hospital discharge into those with good outcomes (Glasgow Outcome Scale, GOS, of 4-5) and poor outcomes (GOS of 1-3).

CSF analysis demonstrated a nearly seven-fold increase in caspase-1 activity in SAH patients compared to controls (p < 0.0001). Within the SAH group, 10 patients (55.6%) had good outcomes and 8 patients (44.4%) had poor outcomes. Mean caspase-1 activity in the poor outcome group was approximately three-times higher than the good outcome group (p = 0.001). Caspase-1 activity was significantly correlated with GOS score (r = - 0.705, p = 0.001). Receiver operating characteristic curve analysis showed that caspase-1 activity can accurately differentiate between patients with good versus poor functional outcome (area under the curve 0.944, p = 0.002).

Inflammasome-derived caspase-1 activity is elevated in the CSF of SAH patients compared to controls and higher levels correlate with worse functional outcome.

Inflammasome-derived caspase-1 activity is elevated in the CSF of SAH patients compared to controls and higher levels correlate with worse functional outcome.

Mesenchymal stem cells (MSCs) in synovial fluid increase after traumatic meniscus injuries. selleck kinase inhibitor However, MSC kinetics in synovial fluid may differ for knees with degenerative meniscus injuries. Furthermore, the combination of surgical repair and synovial MSC transplantation has been found to improve clinical symptoms in patients with degenerative meniscus injury, and in this treatment, only the operation procedure without MSC transplantation might increase MSCs in synovial fluid; if so, soluble factors in synovial fluid will be involved. The purpose is this study was to examine whether MSCs exist in synovial fluid of knees with degenerative meniscus injury, to investigate whether MSCs in synovial fluid increase after harvest of synovium and meniscus repair, and to explore what soluble factors in synovial fluids affect the number of MSCs in synovial fluid.

Subjects were 7 patients with degenerative meniscus injury who underwent meniscal repair and synovial MSC transplantation. Synovial fluid (Pre) was aspirateynovium and meniscus repair. Both CGRP and HGF in synovial fluid can possibly induce MSCs from synovium into synovial fluid. Graphical abstract.

MSCs in synovial fluid were hardly seen in knees with degenerated meniscus injury. They significantly increased 2 weeks after harvest of synovium and meniscus repair. Both CGRP and HGF in synovial fluid can possibly induce MSCs from synovium into synovial fluid. Graphical abstract.To assess the feasibility and the safety of the ultra-minimally invasive (U-MIS) approaches in gynecology, we compared our experience in percutaneous assisted hysterectomy (PSS-H) with a series of 3 mm mini-laparoscopy hysterectomy (m-LPS-H). 126 patients affected by benign and malignant gynecological conditions were considered eligible for minimally invasive hysterectomy 80 patients received PSS approach and 46 m-LPS approach. For both groups, we evaluated intra and perioperative outcomes, post-operative pain and cosmetic outcomes. The baseline characteristics were comparable between the two study groups. As well, no differences were reported in the clinical indications for hysterectomy, principally fibroids/adenomyosis, endometrial hyperplasia and early stage endometrial cancer. The median operative time was 88.5 (40-190) minutes for PSS-H group and 95.0 (42-231) minutes in m-LPS-H group (p = 0.131). No differences were detected in median estimated blood loss (p = 0.104) as well, in the uterine manipulator usage (p = 0.