Human Liver MSCs Retain Their Basic Cellular Properties in Chronically Inflamed Liver Tissue.

Every 25th death worldwide is associated with liver pathology. The development of novel approaches to liver diseases therapy and protocols for maintaining the vital functions of patients on the liver transplant waiting list are urgently needed. Resident mesenchymal stem cells (MSCs) play a significant role in supporting liver tissue integrity and improve the liver condition after infusion.

Impact of antiphospholipid syndrome on placenta and uterine NK cell function: insights from a mouse model.

Antiphospholipid syndrome (APS) is associated with recurrent pregnancy morbidity, yet the underlying mechanisms remain elusive. We performed multifaceted characterization of the biological and transcriptomic signatures of mouse placenta and uterine natural killer (uNK) cells in APS. Histological analysis of APS placentas unveiled placental abnormalities, including disturbed angiogenesis, occasional necrotic areas, fibrin deposition, and nucleated red blood cell enrichment.

Complexity of synovial fluid-derived monocyte-macrophage-lineage cells in knee osteoarthritis.

Synovial fluid (SF)-derived monocyte-macrophage (MON-Mϕ)-lineage cells in knee osteoarthritis (KOA) remain poorly understood. We analyzed SF samples from 420 patients with KOA with effusion. The MON-Mϕ cells accounted for 47.

[Ectopic biliary varices as a cause of portal biliopathy and mechanical jaundice syndrome].

The authors consider ectopic biliary varices as a possible cause of portal biliopathy in extrahepatic portal hypertension. The main diagnostic methods including ultrasound CT, MRI, endoscopic ultrasonography, cholangioscopy, difficulties of differential diagnosis and clinical manifestations of portal biliopathy are presented. Various treatment options including portosystemic shunting and endoscopic biliary decompression are discussed.

Infection of Human Macrophage-Like Cells by African Swine Fever Virus.

Background: The African swine fever (ASF) virus (ASFV) and ASF-like viral sequences were identified in human samples and sewage as well as in different water environments. Pigs regularly experience infections by the ASFV. The considerable stability of the virus in the environment suggests that there is ongoing and long-term contact between humans and the ASFV.

Determining Thrombogenicity: Using a Modified Thrombin Generation Assay to Detect the Level of Thrombotic Event Risk in Lupus Anticoagulant-Positive Patients.

The aim of this study was to determine the thrombogenicity of lupus anticoagulant (LA) antibodies using a modified thrombin generation assay (TGA) with the addition of activated protein C (APC) in a group of 85 patients with LA-positive samples. Of these, 58 patients had clinical manifestations of antiphospholipid syndrome (APS) according to the Sydney criteria classification, i.e.

Transcriptional Readthrough Interrupts Boundary Function in Drosophila.

In higher eukaryotes, distance enhancer-promoter interactions are organized by topologically associated domains, tethering elements, and chromatin insulators/boundaries. While insulators/boundaries play a central role in chromosome organization, the mechanisms regulating their functions are largely unknown. In the studies reported here, we have taken advantage of the well-characterized bithorax complex (BX-C) to study one potential mechanism for controlling boundary function.

Advanced virtual screening enables the discovery of a host-targeting and broad-spectrum antiviral agent.

We employed an advanced virtual screening (AVS) approach to identify potential inhibitors of human dihydroorotate dehydrogenase (DHODH), a validated target for development of broad-spectrum antivirals. We screened a library of 495118 compounds and identified 495 compounds that exhibited better binding scores than the reference ligands involved in the screening. From the top 100 compounds, we selected 28 based on their consensus docking scores and structural novelty.

Antiphospholipid antibody-mediated NK cell cytotoxicity.

Antiphospholipid syndrome (APS) is an autoimmune thrombophilia that is characterised by thrombosis and obstetric complications in the presence of antiphospholipid antibodies (aPL). Pregnancy complications remain a challenging problem for patients with APS, especially during the first trimester. Although natural killer (NK) cells constitute up to 70% of decidual lymphocytes during the first trimester, their contribution to early pregnancy loss in APS is largely unknown.

High-temperature mass spectrometric study and modeling of ceramics based on the Al O -SiO -ZrO system.

Rationale: Materials based on the Al O -SiO -ZrO system are promising for a wide range of high-temperature technological applications, such as thermal barrier coatings in the aviation and space industry or advanced materials in nuclear power reactors. Experimental studies of the ceramics based on this system by the Knudsen effusion mass spectrometric (KEMS) method are of significant interest in designing technological processes for the synthesis and exploitation of the Al O -SiO -ZrO materials.

Methods: Samples of ceramics in the Al O -SiO -ZrO system, including the Al O -ZrO and SiO -ZrO binaries, were prepared by solid-state synthesis.

Phenotypic and functional characterisation of synovial fluid-derived neutrophils in knee osteoarthritis and knee infection.

Objective: An increase in the number of neutrophils (NEUs) has long been associated with infections in the knee joints; however, their impact on knee osteoarthritis (KOA) pathophysiology remains largely unexplored.

Design: This study compared the phenotypic and functional characteristics of synovial fluid (SF)-derived NEUs in KOA and knee infection (INF).

Results: KOA NEUs were characterised by a lower expression of CD11b, CD54, and CD64 and higher expression of CD62L, TLR2, and TLR4 compared with INF NEUs.

Determination of Thrombogenicity Levels of Various Antiphospholipid Antibodies by a Modified Thrombin Generation Assay in Patients with Suspected Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is a hypercoagulable state accompanied by the presence of heterogeneous antiphospholipid antibodies (aPL), which nonspecifically affect hemostasis by the presence of lupus anticoagulans (LA), anticardiolipin antibodies (aCL), antibodies against β2-glycoprotein-I (anti-β2GPI), but also non-criteria antibodies such as antibodies against β2-glycoprotein-I domain I (anti-DI), anti-phosphatidylserine/prothrombin (anti-PS/PT), anti-annexin V, and many others. The main target of the antibodies is the activated protein C (APC) system, the elimination of which can manifest itself as a thrombotic complication. The aim of this study was to determine the thrombogenicity of antibodies using a modified protein C-activated thrombin generation assay (TGA) on a group of 175 samples suspected of APS.

Resistance of Human Liver Mesenchymal Stem Cells to FAS-Induced Cell Death.

Mesenchymal stem cells (MSCs) have a pronounced therapeutic potential in various pathological conditions. Though therapeutic effects of MSC transplantation have been studied for a long time, the underlying mechanisms are still not clear. It has been shown that transplanted MSCs are rapidly eliminated, presumably by apoptosis.

[Ectopic duodenal varices as a cause of difficult diagnosis of bleeding in extrahepatic portal hypertension].

Bleeding from ectopic varicose veins is a rare life-threatening cause of upper gastrointestinal hemorrhage. Alberti first described duodenal varices in 1931. According to the literature, incidence of duodenal varicose veins in patients with portal hypertension is 1-3% of all varicose veins.

Towards a Better Characterisation of Leukemic Cells in Chronic Lymphocytic Leukaemia: Cell-Size Heterogeneity Reflects Their Activation Status and Migratory Abilities.

Chronic lymphocytic leukaemia (CLL) is a genetically, morphologically and phenotypically heterogeneous chronic disease with clinical variability between patients. Whether the significant heterogeneity of cell size within the CLL population contributes to the heterogeneous features of this disease has not been investigated. The present study aimed to characterise the phenotypic and functional properties of two subpopulations of typical CLL cells that differ in cell size: small (s-CLL) and large (l-CLL) CLL cells delineated by forward scatter cytometry.

Transmigration of Neutrophils From Patients With Familial Mediterranean Fever Causes Increased Cell Activation.

Familial Mediterranean fever (FMF) is caused by pyrin-encoding gene mutations and characterized by the self-limiting periods of intense inflammation, which are mainly mediated by a massive influx of polymorphonuclear neutrophils (PMNs) into the inflamed sites. Perturbation of actin polymerization by different pathogens was shown to activate the pyrin inflammasome. Our aim was to test whether cytoskeletal dynamics in the absence of pathogens may cause abnormal activation of PMNs from FMF patients.

Current Promising Biomarkers and Methods in the Diagnostics of Antiphospholipid Syndrome: A Review.

Antiphospholipid syndrome (APS) is a hypercoagulation condition associated with the incidence of heterogenic antiphospholipid antibodies (aPLs), which non-specifically affect hemostasis processes. APS is clinically manifested by recurrent arterial and venous thromboses and reproduction losses. The aPL antibodies, which may induce clinical manifestations of APS, include criteria antibodies anti-cardiolipin, anti-β2-glycoprotein-I, and lupus anticoagulant, but also non-criteria antibodies, for example anti-β2-glycoprotein-I domain I, anti-phosphatidylserine/prothrombin, anti-annexin V, and many others.

Deciphering the complex circulating immune cell microenvironment in chronic lymphocytic leukaemia using patient similarity networks.

The tissue microenvironment in chronic lymphocytic leukaemia (CLL) plays a key role in the pathogenesis of CLL, but the complex blood microenvironment in CLL has not yet been fully characterised. Therefore, immunophenotyping of circulating immune cells in 244 CLL patients and 52 healthy controls was performed using flow cytometry and analysed by multivariate Patient Similarity Networks (PSNs). Our study revealed high inter-individual heterogeneity in the distribution and activation of bystander immune cells in CLL, depending on the bulk of the CLL cells.

[Self-expanding nitinol stents for bleeding from esophageal varices in patients with portal hypertension].

Blakemore probe-obturator was previously preferable for primary hemostasis in patients with bleeding from esophageal varices. Currently, Danis self-expanding nitinol stent became an effective alternative. According to some manufacturers, Danis stent has some advantages over balloon tamponade.

High CXCR3 on Leukemic Cells Distinguishes from in Chronic Lymphocytic Leukemia: Evidence from CD5 and CD5 Clones.

Despite the shared pattern of surface antigens, neoplastic cells in chronic lymphocytic leukemia (CLL) are highly heterogeneous in CD5 expression, a marker linked to a proliferative pool of neoplastic cells. To further characterize CD5 and CD5 neoplastic cells, we assessed the chemokine receptors (CCR5, CCR7, CCR10, CXCR3, CXCR4, CXCR5) and adhesion molecules (CD54, CD62L, CD49d) on the CD5 and CD5 subpopulations, defined by CD5/CD19 coexpression, in peripheral blood of CLL patients ( = 60) subgrouped according to the mutational status ( , = 24; , = 36). CD5 subpopulation showed a high percentage of CXCR3 ( < 0.

17β-Estradiol Promotes Proinflammatory and Procoagulatory Phenotype of Innate Immune Cells in the Presence of Antiphospholipid Antibodies.

Antiphospholipid syndrome (APS) is the most common cause of acquired thrombophilia and recurrent spontaneous miscarriages associated with extended persistence of antiphospholipid antibodies (aPL). How circulating aPL and high-17β-estradiol (E2) environment contribute to the pregnancy complications in APS is poorly defined. Therefore, we aimed to analyse whether E2 could be responsible for the immune cell hyperactivation in aPL- positive (lupus anticoagulant, anti-cardiolipin, anti-β2-glycoprotein) in women.

Hypomethylation of IL1RN and NFKB1 genes is linked to the dysbalance in IL1β/IL-1Ra axis in female patients with type 2 diabetes mellitus.

Inflammation has received considerable attention in the pathogenesis of type 2 diabetes mellitus (T2DM). Supporting this concept, enhanced expression of interleukin (IL)-1β and increased infiltration of macrophages are observed in pancreatic islets of patients with T2DM. Although IL-1 receptor antagonist (IL-1Ra) plays a major role in controlling of IL-1β-mediated inflammation, its counteraction effects and epigenetic alterations in T2DM are less studied.

Anti-domain 1 β2 glycoprotein antibodies increase expression of tissue factor on monocytes and activate NK Cells and CD8+ cells in vitro.

Background: β2-Glycoprotein I (β2GPI) represents the major antigenic target for antiphospholipid antibodies (aPL), with domain 1 (D1) being identified as a risk factor for thrombosis and pregnancy complications in APS. We aimed to analyse the ability of aPL, and particularly anti-D1 β2GPI, to stimulate prothrombotic and proinflammatory activity of immune cells in vitro.

Methods: Peripheral blood mononuclear cells (PBMCs) from 11 healthy individuals were incubated with: (1) "anti-D1(+)"-pooled plasma derived from patients suspected of having APS contained anticardiolipin antibodies (aCL), lupus anticoagulant (LA), anti-β2GPI and anti-D1 β2GPI; (2) "anti-D1(-)"-pooled plasma from patients suspected of having APS contained aCL, LA, anti-β2GPI, and negative for anti-D1 β2GPI; (3) "seronegative"-negative for aPL.

Mesenchymal Stem Cells in the Adult Human Liver: Hype or Hope?

Chronic liver diseases constitute a significant economic, social, and biomedical burden. Among commonly adopted approaches, only organ transplantation can radically help patients with end-stage liver pathologies. Cell therapy with hepatocytes as a treatment for chronic liver disease has demonstrated promising results.

Environmental Triggers of Autoreactive Responses: Induction of Antiphospholipid Antibody Formation.

Antiphospholipid antibodies (aPLs) comprise a diverse family of autoantibodies targeted against proteins with the affinity toward negatively charged phospholipids or protein-phospholipid complexes. Their clinical significance, including prothrombotic potential of anti-cardiolipin antibodies (aCLs), anti-β2-glycoprotein I antibodies (aβ2-GPIs), and lupus anti-coagulant (LA), is well-established. However, the ontogeny of these pathogenic aPLs remains less clear.