Exploring the molecular mechanisms of tirzepatide in alleviating metabolic dysfunction-associated fatty liver in mice through integration of metabolomics, lipidomics, and proteomics.

Clinical studies have suggested that tirzepatide may also possess hepatoprotective effects; however, the molecular mechanisms underlying this association remain unclear. In our study, we performed biochemical analyses of serum and histopathological examinations of liver tissue in mice. To preliminarily explore the molecular mechanisms of tirzepatide on metabolic dysfunction-associated fatty liver disease (MAFLD), liquid chromatography-mass spectrometry (LC-MS) was employed for comprehensive metabolomic, lipidomic, and proteomic analyses in MAFLD mice fed a high-fat diet (HFD).

Association between brachial-ankle pulse wave velocity, obesity-related indices, and the 10-year incident risk score of atherosclerotic cardiovascular disease: The rural Chinese cohort study.

Background And Aims: Although existing evidence suggests that arterial stiffness and obesity impact cardiovascular health, limited studies have been conducted to explore the association between brachial-ankle pulse wave velocity (baPWV), obesity-related indices, and the risk of atherosclerotic cardiovascular disease (ASCVD).

Methods And Results: The study participants were among those who completed the baPWV measurement at the second follow-up examination (during 2018-2020) of the Rural Chinese Cohort Study. Logistic regression models were employed to calculate odds ratios (ORs) and 95 % confidence intervals (CIs) of the 10-year incident risk score of ASCVD associated with baPWV and obesity-related indices.

Mesenchymal Stem Cell Membrane-Camouflaged Liposomes for Biomimetic Delivery of Cyclosporine A for Hepatic Ischemia-Reperfusion Injury Prevention.

Hepatic ischemia-reperfusion injury (HIRI) is a prevalent issue during liver resection and transplantation, with currently no cure or FDA-approved therapy. A promising drug, Cyclosporin A (CsA), ameliorates HIRI by maintaining mitochondrial homeostasis but has systemic side effects due to its low bioavailability and high dosage requirements. This study introduces a biomimetic CsA delivery system that directly targets hepatic lesions using mesenchymal stem cell (MSC) membrane-camouflaged liposomes.

ESF1 and MIPEP proteins promote estrogen receptor-positive breast cancer proliferation and are associated with patient prognosis.

Background: Estrogen receptor-positive (ER+) breast cancer accounts for two-thirds of all breast cancers, and its early and late recurrences still threaten patients' long-term survival and quality of life. Finding candidate tumor antigens and potential therapeutic targets is critical to addressing these unmet needs.

Method: The isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis was employed to identify the differentially expressed proteins (DEPs) between ER + breast cancer and corresponding adjacent normal tissue.

Cross-species metabolomic profiling reveals phosphocholine-mediated liver protection from cold and ischemia/reperfusion.

Cold and ischemia/reperfusion (IR)-associated injuries are seemingly inevitable during liver transplantation and hepatectomy. Because Syrian hamsters demonstrate intrinsic tolerance to transplantation-like stimuli, cross-species comparative metabolomic analyses were conducted with hamster, rat, and donor liver samples to seek hepatic cold and IR-adaptive mechanisms. Lower hepatic phosphocholine contents were found in recipients with early graft-dysfunction and with virus-caused cirrhosis or high model for end-stage liver disease scores (≥30).

FTO deficiency in older livers exacerbates ferroptosis during ischaemia/reperfusion injury by upregulating ACSL4 and TFRC.

Older livers are more prone to hepatic ischaemia/reperfusion injury (HIRI), which severely limits their utilization in liver transplantation. The potential mechanism remains unclear. Here, we demonstrate older livers exhibit increased ferroptosis during HIRI.

Stratifin promotes the malignant progression of HCC via binding and hyperactivating AKT signaling.

Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor with limited treatment options and poor prognosis. In this study, we reveal the pivotal role of Stratifin (SFN), also recognized as 14-3-3σ, in driving HCC progression. Our investigation underscores a substantial upregulation of SFN within HCC tissues, manifesting a significant association with worse prognostic outcomes among HCC patients.

Synergistic antitumor efficacy of aspirin plus lenvatinib in hepatocellular carcinoma via regulating of diverse signaling pathways.

It has been established that monotherapy yields limited efficacy in treating hepatocellular carcinoma (HCC), especially advanced HCC. Increasing evidence from preclinical studies and clinical trials indicates that combining multiple drugs can potentially refine treatment efficacy. Accordingly, it is crucial to explore more effective clinically feasible combination therapies to enhance the treatment outcomes of HCC patients.

Systemic analysis of the prognostic significance and interaction network of miR-26b-3p in cholangiocarcinoma.

MicroRNAs (miRNAs) reportedly play significant roles in the progression of various cancers and hold huge potential as both diagnostic tools and therapeutic targets. Given the ongoing uncertainty surrounding the precise functions of several miRNAs in cholangiocarcinoma (CCA), this research undertakes a comprehensive analysis of CCA data sourced from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The present study identified a novel miRNA, specifically miR-26b-3p, which exhibited prognostic value for individuals with CCA.

Single-cell immune profiling of mouse liver aging reveals Cxcl2+ macrophages recruit neutrophils to aggravate liver injury.

Background And Aims: Immune cells play a crucial role in liver aging. However, the impact of dynamic changes in the local immune microenvironment on age-related liver injury remains poorly understood. We aimed to characterize intrahepatic immune cells at different ages to investigate key mechanisms associated with liver aging.

CircFOXK2 promotes hepatocellular carcinoma progression and leads to a poor clinical prognosis via regulating the Warburg effect.

Background: The Warburg effect is well-established to be essential for tumor progression and accounts for the poor clinical outcomes of hepatocellular carcinoma (HCC) patients. An increasing body of literature suggests that circular RNAs (circRNAs) are important regulators for HCC. However, few circRNAs involved in the Warburg effect of HCC have hitherto been investigated.

Identify Key Genes Correlated to Ischemia-Reperfusion Injury in Aging Livers.

Background: With the intensification of population aging, the proportion of aging livers in the donor pool is increasing rapidly. Compared with young livers, aging livers are more susceptible to ischemia-reperfusion injury (IRI) during liver transplantation, which greatly affects the utilization rate of aging livers. The potential risk factors associated with IRI in aging livers have not been fully elucidated.

Causal associations between changes in lipid profiles and risk of gallstone disease: a two-sample Mendelian randomization study.

Background: Nonalcoholic fatty liver disease (NAFLD) has been linked to gallstone disease (GSD) in observational studies; however, the relationships between certain lipid profiles and GSD remain unclear.

Methods: We adopted a two-sample Mendelian randomization (MR) framework by applying different statistical methods to assess causalities between lipid profiles and GSD. We identified single-nucleotide polymorphisms (SNPs) for blood lipids and NAFLD from separate previous genome-wide association studies (GWASs).

5-Aminolevulinate improves metabolic recovery and cell survival of the liver following cold preservation.

Hibernating thirteen-lined ground squirrels (GS; ) are naturally adapted to prolonged periods of ultraprofound hypothermia (body temperature < 5 ºC) during torpor, and drastic oscillations of body temperature and ischemia/reperfusion-like stress during their short euthermic interbout arousals. Thus, their superior adaptability may hold tremendous promise for the advancement of donor organ cold preservation and subsequent organ transplantation. However, bridging hibernation research and translational medicine has been impeded by a dearth of research tools, till the recent establishment of the GS induced pluripotent stem cells (iPSCs).

Circular RNA circ-102,166 acts as a sponge of miR-182 and miR-184 to suppress hepatocellular carcinoma proliferation and invasion.

Purpose: Multiple circular RNAs (circRNAs) have been reported to be dysregulated in hepatocellular carcinoma (HCC). However, their functions and modes of action are still largely unclear. Identifying key circRNAs and revealing their potential functions and molecular mechanisms is considered important for improving the diagnosis and treatment of HCC.

Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Protect Liver Ischemia/Reperfusion Injury by Reducing CD154 Expression on CD4+ T Cells via CCT2.

As a cause of postoperative complications and early hepatic failure after liver transplantation, liver ischemia/reperfusion injury (IRI) still has no effective treatment during clinical administration. Although the therapeutic potential of mesenchymal stem cells (MSCs) for liver IRI has been previously shown, the underlying mechanisms are not completely clear. It is accepted that MSC-derived extracellular vesicles (MSC-EVs) are newly uncovered messengers for intercellular communication.

A comprehensive analysis of the MAGE family as prognostic and diagnostic markers for hepatocellular carcinoma.

The Melanoma Antigen Gene (MAGE) family is a large, highly conserved group of proteins which was reported to participate in the progression of multiple cancers in humans. However, the function of distinct MAGE genes in hepatocellular carcinoma (HCC) is largely unclear. In this study, we comprehensively evaluated the expression, clinical significance, genetic alteration, interaction network and functional enrichment of MAGEs in HCC.

MSCs ameliorate hepatocellular apoptosis mediated by PINK1-dependent mitophagy in liver ischemia/reperfusion injury through AMPKα activation.

Hepatocyte apoptosis is the main pathophysiological process underlying liver ischemia/reperfusion (I/R) injury. Mitochondrial abnormalities have a vital role in hepatocellular damage. The hepatoprotective effects of mesenchymal stem cells (MSCs) have been previously demonstrated.

A novel protein encoded by circFNDC3B inhibits tumor progression and EMT through regulating Snail in colon cancer.

Background: Colon cancer (CC) is a common malignant cancer. Recently, circFNDC3B was found to exert biological function in multiple cancers. However, it was unclear whether the potential protein encoded by circFNDC3B is involved in carcinogenesis of CC.

Mesenchymal stromal cells attenuate multiple sclerosis IDO-dependent increasing the suppressive proportion of CD5+ IL-10+ B cells.

Multiple sclerosis (MS), one of the autoimmune and inflammatory diseases, is a major cause of neurological disability worldwide. The existing clinical treatments are not curable, and better treatments are urgently needed. Mesenchymal stromal cells (MSCs) have shown promise for treating MS, but the favorable effects and mechanism of MSC therapy on MS are still not fully understood.

An Integrated Nomogram Combining Clinical Factors and Microtubule-Associated Protein 1 Light Chain 3B Expression to Predict Postoperative Prognosis in Patients with Intrahepatic Cholangiocarcinoma.

Purpose: Microtubule-associated protein 1 light chain 3B (LC3B) serves as a key component of autophagy, which is associated with the progression of carcinoma. Yet, it is still unclear whether LC3B is also an independent risk factor for intrahepatic cholangiocarcinoma (ICC). We aim to explore the predictive value of LC3B on prognosis of ICC, and to establish a novel and available nomogram to predict relapse-free survival (RFS) and overall survival (OS) for these patients after curative-intent hepatectomy.