Zobrazení zdroje stránky Enevoldsensamuelsen8687

The prevalence and outcomes of patients who had re-activation of coronavirus disease 2019 (COVID-19) after discharge remain poorly understood. We included 126 consecutively confirmed cases of COVID-19 with 2-month follow-up data after discharge in this retrospective study. The upper respiratory specimen using a reverse-transcription polymerase chain reaction test of three patients (71 years [60-76]) were positive within 11-20 days after their discharge, with an event rate of 19.8 (95%CI 2.60-42.1) per 1,000,000 patient-days. Moreover, all re-positive patients were asymptomatic. Our findings suggest that few recovered patients may still be virus carriers even after reaching the discharge criteria.Treatments against influenza A viruses (IAV) have to be updated regularly due to antigenic drift and drug resistance. Poly (ADP-ribose) polymerases (PARPs) are considered effective therapeutic targets of acute lung inflammatory injury. This study aimed to explore the effects of PARP-1 inhibitor olaparib on IAV-induced lung injury and the underlying mechanisms. Male wild-type C57BL/6 mice were intranasally infected with IAV strain H1N1 to mimic pneumonia experimentally. [https://www.selleckchem.com/products/pf-562271.html PF-562271] Olaparib at different doses was intraperitoneally injected 2 days before and 5 consecutive days after virus stimulation. On day 6 post-infection, lung tissues as well as bronchoalveolar lavage fluid (BALF) were sampled for histological and biochemical analyses. Olaparib increased the survival rate of IAV mice dose-dependently. Olaparib remarkably reduced IAV mRNA expression, myeloperoxidase (MPO) level, and inflammatory cell infiltration in IAV lungs. Moreover, olaparib significantly reduced the level of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-6, and IL-4 and increased IL-10 in IAV lungs. Also, olaparib efficiently reduced IL-6, monocyte chemotactic protein (MCP)-1, granulocyte colony-stimulating factor (G-CSF), TNF-α, chemokine (C-X-C motif) ligand (CXCL)1, CXCL10, chemokine (C-C motif) ligand (CCL)3, and regulated on activation, normal T cell expressed and secreted (RANTES) release in IAV BALF. Olaparib decreased PARylated protein content and p65, IκBα phosphorylation in IAV lung tissues. This study successfully constructed the pneumonia murine model using IAV. Olaparib decreased IAV-induced mortality in mice, lung injury, and cytokine production possibly via modulation of PARP-1/NF-κB axis.Triple negative breast cancer (TNBC) is the most severe type of breast cancer due to the lack of specific targets and rapid metastasis, which result in the poor prognosis. Recently, phosphatidylinositol 3-kinase (PI3K)/Akt pathway has emerged as a potential target for the treatment of TNBC. In our research interest to discover phytochemicals targeting TNBC, we have investigated wikstromol from Wikstroemia indica using the human TNBC MDA-MB-231 cells. The results showed wikstromol at 10 μM inhibited cell growth of MDA-MB-231 cells which was confirmed by MTT assay. Further DAPI staining has revealed wikstromol at 10 μM induced apoptosis of cancer cells, which was associated with the activation of caspase-3 following down-regulation of Bcl-2 as well as up-regulation of Bax, cleaved PARP and phosphorylated p53. Meanwhile, it was observed at 0.1 μM wikstromol suppressed the migration of the cancer cells via decreasing transcription of NF-κB and reducing activity and secretion of downstream MMP-9. In addition, p-PI3K and p-Akt were down-regulated in MDA-MB-231 cells in the presence of wikstromol at 0.1 μM, which indicated inactivation of PI3K/Akt pathway was involved in these inhibitory effects.Taurine is a free amino acid rich in neutrophils, and neutrophils play an important role in the forefront defense against infection. Upon neutrophil activation, taurine reacts with hypochlorous acid (HOCl/OCl-) produced by the myeloperoxidase (MPO) system and gets converted to taurine chloramine (Tau-Cl). Neutrophils have three types of granules, of which the primary granule MPO, secondary granule lactoferrin, and tertiary granule matrix metalloproteinase (MMP)-9 are released into the extracellular space by a process called degranulation. MPO produces hypochlorous acid to kill microorganisms, and the released MPO forms neutrophil extracellular traps (NETs) with released chromatin. Excessive secretion of MPO causes oxidative damage to the surrounding tissues. Lactoferrin exerts antioxidant activity, prevents pro-inflammatory pathway activation, sepsis, and tissue damages, and delays neutrophil apoptosis. Our experimental results show that neutrophils released small amount of granules in an inactive state, and phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionine-leucyl-phenylalanine induced neutrophil degranulation. Tau-Cl inhibited the PMA-induced degranulation of MPO and formation of NETs. While Tau-Cl increased the degranulation of lactoferrin, it had no effect on MMP-9 degranulation. MPO negatively regulated the production of macrophage inflammatory protein (MIP)-2, which stimulates the degranulation and migration of neutrophils. Tau-Cl abrogated MIP-2 expression, suggestive of its inhibitory effect on MPO release. The increase in the intracellular level of MPO may negatively regulates MIP-2 expression, thereby contributing to the further regulation of neutrophil degranulation and migration. Here, we suggest that Tau-Cl selectively inhibits MPO degranulation and stimulates lactoferrin degranulation from neutrophils, thereby protecting inflamed tissues from oxidative damage induced by excessively released MPO.In irreparable radial head fractures, especially if primary stabilizers of the elbow are damaged, the prosthetic replacement prevents instability and stiffness. Concerns have arisen over the use of bipolar press-fit prostheses due to the frequent finding of osteolysis and the risk of instability if compared to monopolar implants. Our aim was to assess midterm clinical and radiological outcomes of bipolar implants and the influence of osteolysis on proximal pain. Seventeen patients with irreparable fractures of the radial head, treated in acute with the same prosthetic model (rHEAD recon SBI/Stryker) between January 2015 and December 2018, were enrolled. Clinical assessment was performed using MEPS and DASH scores; a radiographic study was done to identify heterotopic ossifications and periprosthetic osteolysis. Outcomes at the last follow-up, according to MEPS, were excellent in 10 cases, good in 5 and fair in 2; none of the patients had severe pain or instability. In 3 cases, it was necessary to remove the implant, mainly because of early loosening.