UFMylation: A supervisor of the HIF1α pathway and a potential therapeutic target for anti-PD-1 combination therapy in hypoxic tumors.

Activation of hypoxia signaling has been identified as an innate resistance signature against anti-PD-1 therapy, suggesting its potential as a target for combination treatments. Here, we demonstrate that UFMylation modification of HIF1α stabilizes the protein by antagonizing its ubiquitination and proteasomal degradation under hypoxic conditions. Mechanistically, depletion of or defective UFMylation increases HIF1α binding to p53, promoting its degradation.

Hypothermic oxygenated perfusion inhibits CLIP1-mediated TIRAP ubiquitination via TFPI2 to reduce ischemia‒reperfusion injury of the fatty liver.

The use of fatty livers in liver transplantation has emerged as a crucial strategy to expand the pool of donor livers; however, fatty livers are more sensitive to ischemia‒reperfusion injury (IRI). Excessive congenital inflammatory responses are crucial in IRI. Hypothermic oxygenated perfusion (HOPE) is a novel organ preservation technique that may improve marginal donor liver quality by reducing the inflammatory response.

Apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) promotes stress granule formation via YBX1 phosphorylation in ovarian cancer.

APE1 is an essential gene involved in DNA damage repair, the redox regulation of transcriptional factors (TFs) and RNA processing. APE1 overexpression is common in cancers and correlates with poor patient survival. Stress granules (SGs) are phase-separated cytoplasmic assemblies that cells form in response to environmental stresses.

Hemoperfusion Adsorbents for Removal of Common Toxins in Liver and Kidney Failure: Recent Progress, Challenges, and Prospects.

Liver and kidney failure can lead to extensive accumulation of toxic metabolites in the blood and tissues, such as bilirubin, blood ammonia, endotoxins, cytokines, creatinine, uric acid, and urea, which aggravate the progression of the disease. Hemoperfusion can effectively adsorb and remove toxins from the blood and treat liver and kidney failure. However, the adsorption efficiency and safety of traditional hemoperfusion adsorbents are not ideal.

Hypothermic oxygenated perfusion attenuates DCD liver ischemia-reperfusion injury by activating the JAK2/STAT3/HAX1 pathway to regulate endoplasmic reticulum stress.

Background: Hepatic ischemia-reperfusion injury (IRI) in donation after cardiac death (DCD) donors is a major determinant of transplantation success. Endoplasmic reticulum (ER) stress plays a key role in hepatic IRI, with potential involvement of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway and the antiapoptotic protein hematopoietic-lineage substrate-1-associated protein X-1 (HAX1). In this study, we aimed to investigate the effects of hypothermic oxygenated perfusion (HOPE), an organ preservation modality, on ER stress and apoptosis during hepatic IRI in a DCD rat model.

A novel ameliorated rat model of reversible obstructive jaundice.

Obstructive jaundice is a common clinical symptom generally caused by bile duct stones, inflammatory hyperplasia, and tumors. It is characterized by hyperbilirubinemia and may trigger a variety of complications such as hypotension, kidney injury, endotoxemia, multiple organ dysfunction syndrome, and even death (Pavlidis and Pavlidis, 2018; Liu et al., 2021).

Dysregulation of PD-L1 by UFMylation imparts tumor immune evasion and identified as a potential therapeutic target.

Immunotherapy of PD-L1/PD-1 blockage elicited impressive clinical benefits for cancer treatment. However, the relative low response and therapy resistance highlight the need to better understand the molecular regulation of PD-L1 in tumors. Here, we report that PD-L1 is a target of UFMylation.

Aldehyde Dehydrogenase 2 Protects the Kidney from Ischemia-Reperfusion Injury by Suppressing the IB/NF-B/IL-17C Pathway.

Objective: Ischemia-reperfusion injury (IRI) is an important cause of delayed functional recovery after transplantation. This study is aimed at investigating the molecular mechanism of ALDH2 in a kidney ischemia-reperfusion model based on RNA-seq.

Methods: We performed kidney ischemia-reperfusion in ALDH2 and WT mice and evaluated kidney function and morphology using SCr, HE staining, TUNEL staining, and TEM.

High-strength, antibacterial, antioxidant, hemostatic, and biocompatible chitin/PEGDE-tannic acid hydrogels for wound healing.

Natural polymer hydrogels are widely used in various aspects of biomedical engineering, such as wound repair, owing to their abundance and biosafety. However, the low strength and the lack of function restricted their development and application scope. Herein, we fabricated novel multifunctional chitin/PEGDE-tannic acid (CPT) hydrogels through chemical- and physical-crosslinking strategies, using chitin as the base material, polyethylene glycol diglycidyl ether (PEGDE) and tannic acid (TA) as crosslinking agents, and 90 % ethanol as the regenerative bath.

Synthesis and evaluation of water-soluble imidazolium salt chitin with broad-spectrum antimicrobial activity and excellent biocompatibility for infected wound healing.

Infections caused by bacteria have long constituted a major threat to human health and the economy. Therefore, there is an urgent need to design broad-spectrum antibacterial materials possessing good biocompatibility to treat such infections. Herein, inspired by the good biocompatibility of chitin and antibacterial properties of imidazolium salts, a polysaccharide-based material, imidazolium salt chitin (IMSC), was homogeneously prepared using a facile method with epichlorohydrin as a chemical crosslinker to combine chitin with imidazole to enhance Staphylococcus aureus (S.

Biocompatible and biodegradable chitin-based hydrogels crosslinked by BDDE with excellent mechanical properties for effective prevention of postoperative peritoneal adhesion.

Postoperative peritoneal adhesions are common complications caused by abdominal and pelvic surgery, which seriously impact the quality of life of patients and impose additional financial burdens. Using of biomedical materials as physical barriers to completely isolate the traumatic organ and injured tissue is an optimal strategy for preventing postoperative adhesions. However, the limited efficacy and difficulties in the complete degradation or integration of biomedical materials with living tissues restrict the application of these materials.

Preparation and properties of chitin/silk fibroin biocompatible composite fibers.

In the present world chitin is used enormously in various fields, such as biopharmaceuticals, medical and clinical bioproducts, food packaging, etc. However, its development has been curbed by the impaired performance and cumbersome dissolution process when chitin materials are dissolved and regenerated by physical or chemical methods. To further obtain the regenerated chitin fiber material with improved performance, silk fibroin was introduced into the chitin matrix material, and chitin/silk fibroin biocompatible composite fibers were obtained by formic acid/calcium chloride/ethanol ternary system and top-down wet spinning technology.

Biocompatible Composite Microspheres of Chitin/Ordered Mesoporous Carbon CMK3 for Bilirubin Adsorption and Cell Microcarrier Culture.

Extra bilirubin in the blood can provoke serious illness in patients with severe liver disease. Hemoperfusion is an effective method to remove the extra bilirubin, but its application is limited by the low adsorption efficiency and poor biocompatibility of available adsorbent materials. In this study, chitin/ordered mesoporous carbon CMK3 (Ch/CMK3) microspheres are successfully prepared.

The Study of Magnetoimpedance Effect for Magnetoelectric Laminate Composites with Different Magnetostrictive Layers.

The rectangular magnetoelectric (ME) composites of Metglas/PZT and Terfenol-D/PZT are prepared, and the effects of a magnetostrictive layer's material characteristics on the magnetoimpedance of ME composite are discussed and experimentally investigated. The theoretical analyses show that the impedance is not only dependent on Young's modulus and the magnetostrictive strain of magnetostrictive material but is also influenced by its relative permeability. Compared with Terfenol-D, Metglas possesses significantly higher magnetic permeability and larger magnetostrictive strain at quite low H due to the small saturation field, resulting in the larger magnetoimpedance ratio.

Hypoxia Promotes Pancreatic Cancer Cell Dedifferentiation to Stem-Like Cell Phenotypes With High Tumorigenic Potential by the HIF-1α/Notch Signaling Pathway.

Objectives: This study aimed to investigate the effect and mechanism of hypoxia on pancreatic cancer (PC) cell dedifferentiation and tumorigenic potential.

Methods: Inhibition of hypoxia-inducible factor 1α (HIF-1α) and overexpression of Notch1 in PC HS766T cell lines were by lentiviral transfection. The expression of stem cell-specific markers C-X-C motif chemokine receptor 4, CD44, and Nestin was detected by immunofluorescence and Western blot assays.

Implications of telomerase reverse transcriptase in tumor metastasis.

Metastasis is the main culprit of the great majority of cancerrelated deaths. However, the complicated process of the invasion-metastasis cascade remains the least understood aspect of cancer biology. Telomerase plays a pivotal role in bypassing cellular senescence and sustaining the cancer progression by maintaining telomere homeostasis and genomic integrity.

Polyunsaturated Fatty Acids from Astrocytes Activate PPARγ Signaling in Cancer Cells to Promote Brain Metastasis.

Brain metastasis, the most lethal form of melanoma and carcinoma, is the consequence of favorable interactions between the invading cancer cells and the brain cells. Peroxisome proliferator-activated receptor γ (PPARγ) has ambiguous functions in cancer development, and its relevance in advanced brain metastasis remains unclear. Here, we demonstrate that astrocytes, the unique brain glial cells, activate PPARγ in brain metastatic cancer cells.

Cotargeting the Cell-Intrinsic and Microenvironment Pathways of Prostate Cancer by PI3Kα/β/δ Inhibitor BAY1082439.

Targeting the PI3K pathway is a promising strategy for treating prostate cancers with PTEN-loss. However, current anti-PI3K therapies fail to show long lasting effects. We find that not only the PI3Kα- and PI3kβ-isoforms, but also PI3Kδ, are associated with the epithelial-mesenchymal transition (EMT), a critical process distinguishing indolent from aggressive prostate cancer.

Metformin impairs systemic bile acid homeostasis through regulating SIRT1 protein levels.

Metformin is widely used to treat hyperglycemia. However, metformin treatment may induce intrahepatic cholestasis and liver injury in a few patients with type II diabetes through an unknown mechanism. Here we show that metformin decreases SIRT1 protein levels in primary hepatocytes and liver.

The hepatic FOXQ1 transcription factor regulates glucose metabolism in mice.

Aim/hypothesis: Hepatic forkhead box q1 (FOXQ1) expression levels are regulated by nutritional and pathophysiological status. In this study we investigated the role of FOXQ1 in the regulation of hepatic gluconeogenesis.

Methods: We used multiple mouse and cell models to study the role of FOXQ1 in regulating expression of gluconeogenic genes, and cellular and hepatic glucose production.

Forkhead Box P1 (FOXP1) Transcription Factor Regulates Hepatic Glucose Homeostasis.

Dysregulation of hepatic gluconeogenesis contributes to the pathogenesis of diabetes, yet the detailed molecular mechanisms remain to be fully elucidated. Here we show that FOXP1, a transcriptional repressor, plays a key role in the regulation of systemic glucose homeostasis. Hepatic expression levels of FOXP1 are decreased in diabetic mice.

miR-29c suppresses pancreatic cancer liver metastasis in an orthotopic implantation model in nude mice and affects survival in pancreatic cancer patients.

We investigated mechanisms of pancreatic cancer metastasis and defined the biological role of miR-29c in pancreatic cancer metastasis. After two rounds of cell selection in vivo, pancreatic cancer cells with various metastatic potentials derived from spontaneous liver metastases were used as a model of pancreatic cancer to determine the role of miR-29c in pancreatic cancer metastasis. Pancreatic cancer samples were analyzed for miRNA-29c expression, and these levels were associated with survival between groups.