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Regulated expression of matrix metalloproteinases, inflammatory mediators, and endometrial matrix remodeling by 17beta-estradiol in the immature rat uterus

Abstract Background Administration of a single physiological dose of 17beta-estradiol (E2:40 microg/kg) to the ovariectomized immature rat rapidly induces uterine growth and remodeling. The response is characterized by changes in endometrial stromal architecture during an inflammatory-like response that likely involves activated matrix-metalloproteinases (MMPs). While estrogen is known as an inducer of endometrial growth, its role in specific expression of MMP family members in vivo is poorly characterized. E2-induced changes in MMP-2, -3, -7, and -9 mRNA and protein expression were analyzed to survey regulation along an extended time course 0-72 hours post-treatment. Because E2 effects inflammatory-like changes that may alter MMP expression, we assessed changes in tissue levels of TNF-alpha and MCP-1, and we utilized dexamethasone (600 microg/kg) to better understand the role of inflammation on matrix remodeling. Methods Ovariectomized 21 day-old female Sprague-Dawley rats were administered E2 and uterine tissues were extracted and prepared for transmission electron microscopy (TEM), mRNA extraction and real-time RT-PCR, protein extraction and Western blot, or gelatin zymography. In inhibitor studies, pretreatment compounds were administered prior to E2 and tissues were harvested at 4 hours post-hormone challenge. Results Using a novel TEM method to quantitatively assess changes in stromal collagen density, we show that E2-induced matrix remodeling is rapid in onset (< 1 hour) and leads to a 70% reduction in collagen density by 4 hours. Matrix remodeling is MMP-dependent, as pretreatment with batimastat ablates the hormone effect. MMP-3, -7, and -9 and inflammatory markers (TNF-alpha and MCP-1) are transiently upregulated with peak expression at 4 hours post-E2 treatment. MMP-2 expression is increased by E2 but highest expression and activity occur later in the response (48 hours). Dexamethasone inhibits E2-modulated changes in collagen density and expression of MMPs although these effects are variable. Dexamethasone upregulates MMP-3 mRNA but not protein levels, inhibiting E2-induced upregulation of MMP-7, and -9, and MCP-1 mRNA and protein but not inhibiting the hormone-induced increase in TNF-alpha mRNA. Conclusion The data demonstrate that E2-regulated endometrial remodeling is rapid in onset (<1 hour) and peak expression of MMPs and inflammatory mediators correlates temporally with the period of lowest stromal collagen density during uterine tissue hypertrophy.</p

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Test beam performance of a CBC3-based mini-module for the Phase-2 CMS Outer Tracker before and after neutron irradiation

Author: Abbaneo D.
Abbas M.
Adam W.
Agah A.
Agram J.-L.
Ahmad A.
Ahmed I.
Akpinar A.
Albergo S.
Albert E.
Albrecht A.
Alexander J.
Alhusseini M.
Alibordi M.
Allard Y.
Allongue B.
Ally D.
Almeida J.
Anagnostou G.
Andrea J.
Androsov K.
Anguiano J.
Antonello M.
Apparu D.
Ardila L.
Asenov P.
Asghar M. I.
Assiouras P.
Awais A.
Awan M. I. M.
Azzi P.
Azzurri P.
Bacchetta N.
Backhaus M.
Bagliesi G.
Bahinipati S.
Bainbridge R.
Bakshi A.
Baldinelli G.
Balzer M.
Balázs T.
Baradia S.
Barbagli G.
Bardelli G.
Barinoff M.
Bartek R.
Bartosik N.
Bartók M.
Barvich T.
Basnet A.
Basti A.
Batista Lopes J.
Battacharya R.
Baulieu G.
Bean A.
Beaumont W.
Beccherle R.
Becker R.
Behera P. K.
Behera S. C.
Bellan R.
Benecke A.
Benelli G.
Benvenuti D.
Bergamin G.
Bergauer T.
Berger B.
Berry D. R.
Bertl W.
Bevilacqua T.
Bhardwaj A.
Bhattacharya S.
Bianchi F.
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Bilei G. M.
Bisello D.
Biskop H.
Bizzaglia S.
Blanchot G.
Blekman F.
Bloch D.
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Bonnevaux A.
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Publication venue: Institute of Physics Publishing Ltd
Publication date: 05/05/2023
Field of study

The Large Hadron Collider (LHC) at CERN will undergo major upgrades to increase the instantaneous luminosity up to 5–7.5×10

^{34}

^{-2}

^{-1}

. This High Luminosity upgrade of the LHC (HL-LHC) will deliver a total of 3000–4000 fb-1 of proton-proton collisions at a center-of-mass energy of 13–14 TeV. To cope with these challenging environmental conditions, the strip tracker of the CMS experiment will be upgraded using modules with two closely-spaced silicon sensors to provide information to include tracking in the Level-1 trigger selection. This paper describes the performance, in a test beam experiment, of the first prototype module based on the final version of the CMS Binary Chip front-end ASIC before and after the module was irradiated with neutrons. Results demonstrate that the prototype module satisfies the requirements, providing efficient tracking information, after being irradiated with a total fluence comparable to the one expected through the lifetime of the experiment