c-Kit cells that intercalate with crypt Lgr5 cells are distinctively multipotent in colonic epithelium renewal and repair.

The colonic crypts are principally composed by Lgr5 stem cells and deep crypt secretory (DCS) cells. c-Kit-expressing cells mark DCS cells and supply Wnt3, EGF, and Notch signals to support their neighboring crypt bottom-intermingled Lgr5 cells. However, the role of c-Kit cells beyond supporting Lgr5 cells in colonic epithelium remains unexplored.

RBM39 promotes hepatocarcinogenesis by regulating RFX1's alternative splicing and subsequent activation of integrin signaling pathway.

Alternative splicing (AS) is crucial for tumor cells as it regulates protein expression and produces various protein isoforms, which can have diverse or even opposing roles in tumor growth and metastasis. Despite its significance, the role of AS and related splicing factors, particularly splicing-related messenger ribonucleoproteins (mRNPs), in hepatocarcinogenesis, is poorly understood. High-throughput transcriptome sequencing of HCC patients revealed that the spliceosome pathway might play a significant role in HCC development.

Targeting FDFT1 Reduces Cholesterol and Bile Acid Production and Delays Hepatocellular Carcinoma Progression Through the HNF4A/ALDOB/AKT1 Axis.

Targeting cholesterol metabolism is a novel direction for tumor therapy. Unfortunately, the current use of statins for hepatocellular carcinoma (HCC) is controversial. Herein, farnesyl-diphosphate farnesyltransferase 1 (FDFT1) is identified as a novel target for treating HCC and a potential alternative to statins.

Perfluorohexane nanodroplet-assisted mechanical high intensity focused ultrasound cavitation: A strategy for hepatocellular carcinoma treatment.

The activation of immune-stimulatory molecules is critical for effective antitumor immunotherapy. Mechanical high-intensity focused ultrasound (mHIFU) sustains this activation in tumor cell debris through cavitation. To enhance cavitation, perfluorohexane nanodroplets (NDs-PFH) were utilized in this study to lower the cavitation threshold during mHIFU ablation.

The Lactate-Primed KAT8‒PCK2 Axis Exacerbates Hepatic Ferroptosis During Ischemia/Reperfusion Injury by Reprogramming OXSM-Dependent Mitochondrial Fatty Acid Synthesis.

Recipients often suffer from hyperlactatemia during liver transplantation (LT), but whether hyperlactatemia exacerbates hepatic ischemia-reperfusion injury (IRI) after donor liver implantation remains unclear. Here, the role of hyperlactatemia in hepatic IRI is explored. In this work, hyperlactatemia is found to exacerbate ferroptosis during hepatic IRI.

Inhibition of IRE-1α Alleviates Pyroptosis and Metabolic Dysfunction-Associated Steatohepatitis by Suppressing Gasdermin D.

Objectives: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for cirrhosis and hepatocellular carcinoma, for which there is currently no effective treatment. This study aimed to investigate the regulatory mechanism between endoplasmic reticulum stress (ER stress) and pyroptosis in the liver under the context of MASH.

Methods And Results: Pyroptosis was examined in both in vivo and in vitro ER stress models.

Integrated Single-Cell and Spatial Transcriptome Reveal Metabolic Gene SLC16A3 as a Key Regulator of Immune Suppression in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers, usually diagnosed at an advanced stage. Metabolic reprogramming plays a significant role in HCC progression, probably related to immune evasion, yet the key gene is unclear. In this study, six metabolism-related genes with prognostic implications were screened.

Prognostic Implications of MRI-assessed Intratumoral Fat in Hepatocellular Carcinoma: An Asian and European Cohort Study.

Background The clinicopathologic-radiologic and prognostic characteristics of intratumoral fat in hepatocellular carcinoma (HCC) are critical for personalized treatment but remain understudied. Purpose To investigate the clinicopathologic-radiologic associations and prognostic implications of MRI-assessed intratumoral fat in HCCs. Materials and Methods This retrospective cohort study included consecutive adult patients who underwent resection for solitary HCCs and preoperative contrast-enhanced MRI from two tertiary-care hospitals in East Asia (March 2011 to December 2021) and Western Europe (September 2012 to December 2019).

UBAP2 contributes to radioresistance by enhancing homologous recombination through SLC27A5 ubiquitination in hepatocellular carcinoma.

Radiotherapy stands as an effective method in the clinical treatment of hepatocellular carcinoma (HCC) patients. However, both primary and acquired radioresistance limit its clinical application in HCC. Therefore, investigating the mechanism of radioresistance may provide other options for treating HCC.

Peripheral Injection of hUC-MSCs in the Treatment of Acute Liver Failure: A Pre-Clinical Cohort Study in Rhesus Monkeys.

Background: Using a toxin-induced lethal acute liver failure (ALF) monkey model, we have recently shown that early peripheral infusion of human umbilical cord mesenchymal stem cells (hUC-MSCs) can alleviate liver damage and improve animal survival by suppressing the activation of circulating monocytes and the subsequent cytokine storm. Here, we explored whether the administration of hUC-MSCs could still improve ALF when the cytokine storm is fully developed.

Method: We treated ALF monkeys with peripheral delivery of hUC-MSCs at 48 hr after toxin challenge.

Suppression of STK39 weakens the MASLD/MASH process by protecting the intestinal barrier.

STK39 is reportedly a critical negative regulator of intestinal barrier. Pharmacological targeting of STK39 is expected to protect the intestinal barrier and thereby weaken metabolic dysfunction-associated steatohepatitis (MASH); Proximal colon biopsy tissues from patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and those without MASLD were analyzed for STK39 expression. Wildtype (WT) mice and systemic STK39 gene knockout (STK39) male mice were fed a normal diet or a high-fat methionine-choline deficient diet (HFMCD) for 8 weeks.

Novel prognostic biomarkers in nasopharyngeal carcinoma unveiled by mega-data bioinformatics analysis.

Nasopharyngeal carcinoma (NPC) is commonly diagnosed at an advanced stage with a high incidence rate in Southeast Asia and Southeast China. However, the limited availability of NPC patient survival data in public databases has resulted in less rigorous studies examining the prediction of NPC survival through construction of Kaplan-Meier curves. These studies have primarily relied on small samples of NPC patients with progression-free survival (PFS) information or data from head and neck squamous cell carcinoma (HNSCC) studies almost without NPC patients.

Apparent diffusion coefficient and tissue stiffness are associated with different tumor microenvironment features of hepatocellular carcinoma.

Objectives: To investigate associations between tissue diffusion, stiffness, and different tumor microenvironment features in resected hepatocellular carcinoma (HCC).

Methods: Seventy-two patients were prospectively included for preoperative magnetic resonance (MR) diffusion-weighted imaging and MR elastography examination. The mean apparent diffusion coefficient (ADC) and stiffness value were measured on the central three slices of the tumor and peri-tumor area.

Whole-Genome DNA Methylation Profiling of Intrahepatic Cholangiocarcinoma Reveals Prognostic Subtypes with Distinct Biological Drivers.

Unlabelled: Intrahepatic cholangiocarcinoma (iCCA) is the second most prevalent primary liver cancer. Although the genetic characterization of iCCA has led to targeted therapies for treating tumors with FGFR2 alterations and IDH1/2 mutations, only a limited number of patients can benefit from these strategies. Epigenomic profiles have emerged as potential diagnostic and prognostic biomarkers for improving the treatment of cancers.

Repaglinide restrains HCC development and progression by targeting FOXO3/lumican/p53 axis.

Purpose: The recent focus on the roles of N-linked glycoproteins in carcinogenesis across various malignancies has prompted our exploration of aberrantly expressed glycoproteins responsible for HCC progression and potential therapeutic strategy.

Methods: Mass spectrometry was applied to initially identify abnormally expressed glycoproteins in HCC, which was further assessed by immunohistochemistry (IHC) staining. The role of selected glycoprotein on HCC development and underlying mechanism was systematically investigated by colony formation, mouse xenograft, RNA-sequencing and western blot assays, etc.

METTL14/miR-29c-3p axis drives aerobic glycolysis to promote triple-negative breast cancer progression though TRIM9-mediated PKM2 ubiquitination.

The energy metabolic rearrangement of triple-negative breast cancer (TNBC) from oxidative phosphorylation to aerobic glycolysis is a significant biological feature and can promote the malignant progression. However, there is little knowledge about the functional mechanisms of methyltransferase-like protein 14 (METTL14) mediated contributes to TNBC malignant progression. Our study found that METTL14 expression was significantly upregulated in TNBC tissues and cell lines.

S14G-humanin confers cardioprotective effects against chronic adrenergic and pressure overload-induced heart failure in mice.

S14G-humanin (HNG), an analog of the mitochondria-derived peptide humanin, has demonstrated protective effects against various cardiovascular diseases. However, the specific pharmacological effects of HNG in heart failure (HF) have not been previously reported. Therefore, in this study, we aimed to investigate the potential protective effect of HNG in HF using a mouse model.

Hepatocyte-specific HDAC3 ablation promotes hepatocellular carcinoma in females by suppressing Foxa1/2.

Background: Hepatocellular carcinoma (HCC), the most common primary liver cancer, prevails mainly in males and has long been attributed to androgens and higher circumstantial levels of interleukin-6 (IL-6) produced by resident hepatic macrophages.

Methods: Constitutively hepatocyte-specific histone deacetylase 3 (HDAC3)-deficient (HDAC3) mice and constitutively hepatocyte-specific HDAC3 knockout and systemic IL-6 simultaneously ablated (HDAC3& IL-6) mice were used in our study to explore the causes of sex differences in HCC. Additionally, we performed human HCC tissues with an IHC score.

HDAC11 is related to breast cancer prognosis and inhibits invasion and proliferation of breast cancer cells.

Objective: Histone deacetylases (HDACs) not only regulate histone acetylation but also participate in many pathophysiologic processes, especially the development of cancer, including breast cancer. However, whether Histone deacetylase 11 can influence breast cancer is still unknown. This study investigated the relationship between HDAC11 expression in breast cancers and clinicopathologic parameters, and used small interference RNA (siRNA) to determine the biological behavioural changes after knockdown of HDAC11.

Genetic Association of Circulating Adipokines with Risk of Idiopathic Pulmonary Fibrosis: A Two-Sample Mendelian Randomization Study.

Purpose: The causal relationships between circulating adipokines and idiopathic pulmonary fibrosis (IPF) are yet to be established. We performed a two-sample Mendelian randomization (MR) study to investigate the causal roles of adipokines on IPF risk.

Methods: We analyzed the summary data from genome-wide association studies (GWAS), including adiponectin, leptin, resistin and monocyte chemoattractant protein-1 (MCP-1) and IPF.

PI3K-CCL2-CCR2-MDSCs axis: A potential pathway for tumor Clostridia-promoted CD 8 T lymphocyte infiltration in bile tract cancers.

Background: Most patients with resected bile tract cancers (BTCs) survive for less than 5 years; however, some achieve better prognosis. The tumor microbiome can improve survival by regulating the tumor immune microenvironment. However, whether the tumor microbiome promotes immune cell infiltration in BTCs is unknown.

Comparison of primary hepatic neuroendocrine tumors and non-hepatitis B non-hepatitis C hepatocellular carcinoma on contrast-enhanced ultrasound.

Objective: The purpose of this study was to compare the sonographic features of primary hepatic neuroendocrine tumors (PHNETs) to those of non-hepatitis B and non-hepatitis C hepatocellular carcinoma (NBNC-HCC) on contrast-enhanced ultrasound (CEUS).

Materials And Methods: Fourteen patients with a mean age of 56.9 ± 12.

Glutamine synthetase-negative hepatocellular carcinoma has better prognosis and response to sorafenib treatment after hepatectomy.

Background: Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear.

Methods: We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining.

Testicular torsion diagnosis and injury assessment using photoacoustic oxygenation imaging.

Testicular torsion (TT) is a medical emergency that requires immediate diagnostic evaluation. Photoacoustic imaging (PAI) has the potential to provide spatially resolved oxygen saturation (sO), which can serve as a valuable marker in TT diagnosis. We investigated the potential of PAI as an alternative method for TT diagnosis and testicular injury assessment.