Metabolic Mode of Alginate-Encapsulated Human Mesenchymal Stromal Cells as a Background for Storage at Ambient Temperature.

Human mesenchymal stromal cells (MSCs) are attractive for both medical practice and biomedical research. Nonfreezing short-term storage may provide safe and simple transportation and promote the practical use of MSCs. We aimed to determine the duration of efficient storage at ambient temperature (22°C) of human dermal MSCs in different three-dimensional organization and to investigate the role of cell metabolic mode in the resistance to the ambient storage damaging factors.

Inflammation remains a dynamic component of portal hypertension in regressive alcohol-related cirrhosis.

Background: Portal hypertension (PH) resulting from static and dynamic intrahepatic changes drives liver-related complications even after removing the underlying aetiological factor.

Objective: We investigated the impact of inflammation on the dynamic component of PH during disease regression in animal models of toxin-induced cirrhosis and patients with alcohol-related cirrhosis.

Methods: In mice, cirrhosis was induced via toxin application for 12 weeks followed by toxin-withdrawal allowing for one or 2 weeks of regression.

War exposure and changes in eating behaviours in Ukrainian school-aged children: A cross-sectional online survey.

The war in Ukraine has exposed children to extremely high levels of acute and chronic stressors, which can impact their eating behaviour (EB). We aimed to determine the prevalence of war-induced, stress-related disruptions in EB of Ukrainian children. We conducted a cross-sectional online survey among parents of 5- to 17-year-old children, who had experienced the war in Ukraine in February-May 2023.

Portal hypertension and its prognostic implications in patients with Wilson's disease.

Background And Aims: Wilson's disease may progress to cirrhosis and clinically significant portal hypertension (CSPH). We aimed to assess the prevalence and prognostic impact of CSPH-related features on hepatic decompensation and transplant-free survival in patients with Wilson's disease.

Methods And Results: About 137 patients with Wilson's disease (Leipzig score ≥4), followed for a median observation period of 9.

Theory-based cryopreservation mode of mesenchymal stromal cell spheroids.

Cryopreservation of spheroids requires development of new improved methods. The plasma membranes permeability coefficients for water and cryoprotectants determine time characteristics of mass transfer through the cell membranes, and therefore the optimal modes of cells cryopreservation. Here we proposed an approach to cryopreservation of multicellular spheroids which considers their generalized characteristics as analogues of the membranes' permeability coefficients of the individual cells.

Topical Application of Autologous Plasma-Derived Plasminogen Accelerates Healing of Chronic Foot Ulcers in Type 2 Diabetes Patients.

Plasminogen (Pg) is currently considered a master regulator of wound healing, but the molecular mechanisms of its efficacy in improving impaired closure of chronic skin ulcers in type 2 diabetes patients remain unclear. Here, we investigated wound healing effects of autologous plasma-derived Pg in diabetes patients with chronic foot ulcers and evaluated Pg-induced changes in levels of key protein markers related to wound repair. Type 2 diabetes patients with chronic wounds of lower extremities were included in the study and received topical applications of Pg in a dose of 1.

The resilience of Ukrainian scientists.

We have asked Ukrainian scientists how they have been able to persist in pursuing their research since the beginning of the full-scale invasion of Ukraine by the Russian Federation in February of 2022. We thank the scientists who were willing to share their thoughts and experiences; the views expressed are those of the contributors alone.

STAT3 is a genetic modifier of TGF-beta induced EMT in KRAS mutant pancreatic cancer.

Oncogenic mutations in KRAS are among the most common in cancer. Classical models suggest that loss of epithelial characteristics and the acquisition of mesenchymal traits are associated with cancer aggressiveness and therapy resistance. However, the mechanistic link between these phenotypes and mutant KRAS biology remains to be established.

Transcriptomic signatures of progressive and regressive liver fibrosis and portal hypertension.

Persistent liver injury triggers a fibrogenic program that causes pathologic remodeling of the hepatic microenvironment (i.e., liver fibrosis) and portal hypertension.

Evaluation of potential hepatic recompensation criteria in patients with PBC and decompensated cirrhosis.

Background: Aetiological therapy improves liver function and may enable hepatic recompensation in decompensated cirrhosis.

Aims: We explored the potential for recompensation in patients with decompensated primary biliary cholangitis (PBC) - considering a biochemical response to ursodeoxycholic acid (UDCA) according to Paris-II criteria as a surrogate for successful aetiological treatment.

Methods: Patients with PBC were retrospectively included at the time of first decompensation.

FXR-FGF19 signaling in the gut-liver axis is dysregulated in patients with cirrhosis and correlates with impaired intestinal defence.

Background And Aims: Experimental studies linked dysfunctional Farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling to liver disease. This study investigated key intersections of the FXR-FGF19 pathway along the gut-liver axis and their link to disease severity in patients with cirrhosis.

Methods: Patients with cirrhosis undergoing hepatic venous pressure gradient measurement (cohort-I n = 107, including n = 53 with concomitant liver biopsy; n = 5 healthy controls) or colonoscopy with ileum biopsy (cohort-II n = 37; n = 6 controls) were included.

Oncogenic dependency plays a dominant role in the immune response to cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest human malignancies. Advanced PDAC is considered incurable. Nearly 90% of pancreatic cancers are caused by oncogenic KRAS mutations.

STAT3 is a genetic modifier of TGF-beta induced EMT in KRAS mutant pancreatic cancer.

Oncogenic mutations in KRAS are among the most common in cancer. Classical models suggest that loss of epithelial characteristics and the acquisition of mesenchymal traits are associated with cancer aggressiveness and therapy resistance. However, the mechanistic link between these phenotypes and mutant KRAS biology remains to be established.

Hypothermic organ perfusion in the 2020s: mixing the benefits of low temperatures and dynamic flow outside the body.

The cold chain supply of donor organs for transplantation has been an integral part of the delivery of transplant clinical services over the past five decades. Within the technologies used for this, hypothermic machine perfusion (HMP) was a concept, which was attractive to maintain organs under optimal conditions outside the body, and many early research studies on HMP were reported. However, it took the arrival of important new concepts to ensure that HMP was logistically feasible and valuable from an organ physiology perspective within the clinical pathways.

Assessment of portal hypertension severity using machine learning models in patients with compensated cirrhosis.

Background & Aims: In individuals with compensated advanced chronic liver disease (cACLD), the severity of portal hypertension (PH) determines the risk of decompensation. Invasive measurement of the hepatic venous pressure gradient (HVPG) is the diagnostic gold standard for PH. We evaluated the utility of machine learning models (MLMs) based on standard laboratory parameters to predict the severity of PH in individuals with cACLD.

Splenectomy ameliorates portal pressure and anemia in animal models of cirrhotic and non-cirrhotic portal hypertension.

Purpose: Portal hypertension (PH)-associated splenomegaly is caused by portal venous congestion and splanchnic hyperemia. This can trigger hypersplenism, which favors the development of cytopenia. We investigated the time-dependent impact of splenectomy on portal pressure and blood cell counts in animal models of non-cirrhotic and cirrhotic PH.

Distinct prognostic value of different portal hypertension-associated features in patients with primary biliary cholangitis.

Background: Primary biliary cholangitis (PBC) may progress to cirrhosis and clinically significant portal hypertension (CSPH). This study assesses different features of CSPH and their distinct prognostic impact regarding decompensation and survival in patients with PBC.

Methods: Patients with PBC were identified during a database query of our digital patient reporting system.

Distinct structural and dynamic components of portal hypertension in different animal models and human liver disease etiologies.

Background And Aims: Liver fibrosis is the static and main (70%-80%) component of portal hypertension (PH). We investigated dynamic components of PH by a three-dimensional analysis based on correlation of hepatic collagen proportionate area (CPA) with portal pressure (PP) in animals or HVPG in patients.

Approach And Results: Different animal models (bile duct ligation: n = 31, carbon tetrachloride: n = 12, thioacetamide: n = 12, choline-deficient high-fat diet: n = 12) and patients with a confirmed single etiology of cholestatic (primary biliary cholangitis/primary sclerosing cholangitis: n = 16), alcohol-associated (n = 22), and metabolic (NASH: n = 19) liver disease underwent CPA quantification on liver specimens/biopsies.

Nuclear receptors in liver fibrosis.

Nuclear receptors are ligand-activated transcription factors that regulate gene expression of a variety of key molecular signals involved in liver fibrosis. The primary cellular driver of liver fibrogenesis is activated hepatic stellate cells. Different nuclear receptors regulate the hepatic expression of pro-inflammatory and pro-fibrogenic cytokines that promote the transformation of hepatic stellate cells into fibrogenic myofibroblasts.

KRAS drives immune evasion in a genetic model of pancreatic cancer.

Immune evasion is a hallmark of KRAS-driven cancers, but the underlying causes remain unresolved. Here, we use a mouse model of pancreatic ductal adenocarcinoma to inactivate KRAS by CRISPR-mediated genome editing. We demonstrate that at an advanced tumor stage, dependence on KRAS for tumor growth is reduced and is manifested in the suppression of antitumor immunity.