Hepatic hypoxia

AIMS: Kidney disease often leads to anemia due to a defect in the renal production of the erythroid growth factor erythropoietin (EPO), which is produced under the positive regulation of hypoxia-inducible transcription factors (HIFs). Chemical compounds that inhibit HIF-prolyl hydroxylases (HIF-PHs), which suppress HIFs, have been developed to reactivate renal EPO production in renal anemia patients. Currently, multiple HIF-PH inhibitors, in addition to conventional recombinant EPO reagents, are used for renal anemia treatment...

Emerging evidence indicates the presence of vascular abnormalities and ischemia in biliary atresia (BA), although specific mechanisms remain undefined. This study examined both human and experimental BA. Structural and hemodynamic features of hepatic arteries were investigated by Doppler ultrasound, indocyanine green angiography, microscopic histology, and invasive arterial pressure measurement. Opal multiplex immunohistochemistry, western blot, and RT-PCR were applied to assess Notch3 expression and the phenotype of hepatic arterial smooth muscle cells (HASMCs)...

PURPOSE: Liver function of intensive care patients is routinely monitored by static blood pathology. For specific indications, liver specific cytochrome activity may be measured by the commercially available maximum liver function capacity (LiMAx) test via quantification of the cytochrome P450 1A2 (CYP1A2) dependent C-methacetin metabolism. Sedation with the volatile anesthetic isoflurane was suspected to abrogate the correlation of LiMAx test with global liver function. We hypothesized that isoflurane has a CYP1A2-activity and LiMAx test result decreasing effect...

AIM: Precision liver resection is considered the gold standard in liver surgery. Therefore, optimizing the resection of lesions and minimizing unnecessary time of liver ischemia and hypoxia have become focal points. METHODS: A total of 96 patients with primary liver cancer admitted to Cangzhou People's Hospital from January 2017 and December 2019 were included in this retrospective study, and divided into two groups according to the different surgical treatment, with 50 cases in the control group (conventional hepatic resection) and 46 cases in the observation group (precision liver resection)...

6-Gingerol, the main bioactive compound of ginger, has antioxidant, anti-inflammatory, anti-cancer and neuroprotective effects. However, it is unclear whether 6-Gingerol has protective effects against hepatic ischemia/reperfusion (I/R) injury. In this study, the mouse liver I/R injury model and the mouse AML12 cell hypoxia/reoxygenation (H/R) model were established by pretreatment with 6-Gingerol at different concentrations to explore the potential effects of 6-Gingerol. Serum transaminase levels, liver necrotic area, cell viability, inflammatory response, and cell apoptosis were used to assess the effect of 6-Gingerol on hepatic I/R or cell H/R injury...

Early allograft dysfunction (EAD) is a functional hepatic insufficiency within a week of orthotopic liver transplantation (OLT) and is associated with morbidity and mortality. The etiology of EAD is multifactorial and largely driven by ischemia reperfusion injury (IRI), a phenomenon characterized by oxygen scarcity followed by paradoxical oxidative stress and inflammation. With the expanded use of marginal allografts more susceptible to IRI, the incidence of EAD may be increasing. This necessitates an in-depth understanding of the innate molecular mechanisms underlying EAD and interventions to mitigate its impact...

The celiacomesenteric trunk (CMT), an exceedingly rare anatomic variant uniting the celiac artery and superior mesenteric artery (SMA), holds significant clinical and surgical implications. Despite its rarity, understanding these implications is crucial for effective management. This report outlines the case of a 99-year-old female presenting with septic shock and abdominal pain, with imaging revealing an incidental CMT. This paper aims to elucidate the surgical implications associated with CMT through a comprehensive case review and literature search...

In hepatocellular carcinoma (HCC), classical cancer stem cells (CSC) markers were shared by normal stem cells, targeting which may hinder hepatic regeneration and cause liver failure. Additionally, the spatial structure of CSC still remained elusive. To address these limitations, we undertook a comprehensive study combining single-cell data (56,022 cells from 20 samples) and spatial data (38,191 spots from eight samples) to obtain CSC signature and uncover its spatial structure. Utilizing the CytoTRACE algorithm, we discretely identified CSC, which displayed upregulated proliferation pathways regulated by HIF1A...

BACKGROUND: Positron Emission Tomography (PET) with combined [18 F]-FDG and [11 C]-acetate (dual-tracer) is used for the management of hepatocellular carcinoma (HCC) patients, although its prognostic value and underlying molecular mechanism remain poorly understood. We hypothesized that radiotracer uptake might be associated with tumor hypoxia and validated our findings in public and local human HCC cohorts. METHODS: Twelve orthotopic HCC xenografts were established using MHCC97L cells in female nude mice, with 5 having undergone hepatic artery ligation (HAL) to create tumor hypoxia in vivo...

Gilthead seabream (Sparus aurata) is an important species in Mediterranean aquaculture. Rapid intensification of its production and sub-optimal husbandry practices can cause stress, impairing overall fish performance and raising issues related to sustainability, animal welfare, and food safety. The advent of next-generation sequencing technologies has greatly revolutionized the study of fish stress biology, allowing a deeper understanding of the molecular stress responses. Here, we characterized for the first time, using RNA-seq, the different hepatic transcriptome responses of gilthead seabream to common aquaculture challenges, namely overcrowding, net handling, and hypoxia, further integrating them with the liver proteome and metabolome responses...

BACKGROUND: Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). However, the mechanisms underlying immune and metabolic derangement in patients with advanced HBV-ACLF are unclear. AIM: To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic disorders...

BACKGROUND: Obesity is associated with extensive white adipose tissue (WAT) expansion and remodeling. Healthy WAT expansion contributes to the maintenance of energy balance in the liver, thereby ameliorating obesity-related hepatic steatosis. Tissue-resident mesenchymal stromal cell populations, including PDGFRβ + perivascular cells, are increasingly recognized pivotal as determinants of the manner in which WAT expands. However, the full array of regulatory factors controlling WAT stromal cell functions remains to be fully elucidated...

BACKGROUND AND AIM: Respiratory complications in liver cirrhosis can occur due to various mechanisms, such as ascites causing restricted lung expansion and opening of intrapulmonary vascular shunts due to high portal pressures. We aimed to study the effects of the liver dysfunction on the lungs by evaluating arterial blood gas (ABG) and pulmonary function test (PFT) of all study subjects. SUBJECTS AND METHODS: A cross-sectional study was done between August 2020 and September 2022...

Non-alcoholic fatty liver disease (NAFLD) has a high global prevalence and affects approximately one-third of adults, owing to high-fat dietary habits and a sedentary lifestyle. The role of hypoxia-inducible factor 2α (HIF-2α) in NAFLD progression remains unknown. This study aimed to investigate the effects of chronic hypoxia on NAFLD progression by examining the role of hypoxia-inducible factor 2α (HIF-2α) activation and that of hepatic stellate cell (HSC)-derived myofibroblasts through glutaminolysis...

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and is highly metastatic. Our prior studies have demonstrated the critical role of axon guidance pathway genes in PDAC and the connection between neuronal development and the tumor microenvironment. A recent study newly identified 20 neuronal development genes [disks large homolog 2 ( DLG2 ), neuron-glial-related cell adhesion molecule ( NRCAM ), neurexin3 ( NRXN3 ), mitogen-activated protein kinase 10 ( MAPK10 ), platelet-derived growth factor D ( PDGFD ), protein kinase C epsilon ( PRKCE ), potassium calcium-activated channel subfamily M alpha 1 ( KCNMA1 ), polycystic kidney and hepatic disease 1 ( PKHD1 ), neural cell adhesion molecule 1 ( NCAM1 ), neuregulin-1 ( NRG1 ), zinc finger protein 667 ( ZNF667 ), cystic fibrosis transmembrane conductance regulator ( CFTR ), acyl-CoA medium-chain synthetase-3 ( ACSM3 ), complement 6 ( C6 ), protein tyrosine phosphatase receptor type M ( PTPRM ), hypoxia-inducible factor 1 alpha ( HIF1A ), adenylyl cyclase 5 ( ADCY5 ), adherens junctions-associated protein 1 ( AJAP1 ), neurobeachin ( NBEA ), sodium voltage-gated channel alpha subunit 9 ( SCN9A )] that are associated with perineural invasion and poor prognosis of PDAC...

Hepatic ischemia reperfusion (I/R) injury is a common clinical complication. X-box binding protein 1 (XBP1), as a critical regulator of the endoplasmic reticulum stress, has been implicated in a variety of diseases. In this study, we aimed to investigate the effects and the underlying mechanism of XBP1 in the progression of hepatic I/R injury. Hepatocyte-specific XBP1 knockout mice, multiple viral delivery systems and specific pharmacological inhibitors were applied in vivo in a partial hepatic I/R injury mouse model and in vitro in a cell model of hypoxia-reoxygenation (H/R) injury...

Colorectal cancer metastasizes predominantly to the liver but also to the lungs and the peritoneum. The presence of extra-hepatic metastases limits curative (surgical) treatment options and is associated with very poor survival. The mechanisms governing multi-organ metastasis formation are incompletely understood. Here, we tested the hypothesis that the site of tumor growth influences extra-hepatic metastasis formation. To this end, we implanted murine colon cancer organoids into the primary tumor site (i.e...

Type-1 Diabetes Mellitus (T1DM) manifests due to pancreatic beta cell destruction, causing insulin deficiency and hyperglycaemia. Current therapies are inadequate for brittle diabetics, necessitating pancreatic islet transplants, which however, introduces its own set of challenges such as paucity of donors, rigorous immunosuppression and autoimmune rejection. Organoid technology represents a significant stride in the field of regenerative medicine and bypasses donor-based approaches. Hence this article focuses on strategies enhancing the in vivo engraftment of islet organoids (IOs), namely vascularization, encapsulation, immune evasion, alternative extra-hepatic transplant sites and 3D bioprinting...

BACKGROUND: Transplantation of mesenchymal stem cells (MSCs) is a newly developed strategy for treating acute liver failure (ALF). Nonetheless, the low survival rate of MSCs after transplantation and their poor homing to damaged tissues limit the clinical application of MSCs. The research assessed whether hypoxic preconditioning (HPC) can improve the biological activity of human amniotic mesenchymal stem cells (hA-MSCs), promote their homing ability to the liver of mice with ALF, and influence liver tissue repair...

Liver sinusoidal endothelial cells (LSECs) have an important role in hepatic ischemia‑reperfusion injury (I/R), but the specific molecular mechanism of action is unknown. LSEC proliferation is regulated and fenestration is maintained via the Sentrin/SUMO‑specific protease 1 (SENP1)/hypoxia‑inducible factor‑1α (HIF‑1α) signaling axis under hypoxic conditions. In the present study, a hypoxia‑reoxygenation (H‑R) injury model was established using mouse LSECs to explore the relationship between SENP1 and H‑R injury in vitro , and the specific underlying mechanism was identified, revealing new targets for the clinical attenuation of hepatic I/R injury...