An oncoprotein CREPT functions as a co-factor in MYC-driven transformation and tumor growth.

Understanding the mechanisms behind MYC-driven oncogenic transformation could pave the way for identifying novel drug targets. This study explored the role of CREPT in MYC-induced malignancy by generating MYC-transformed mouse embryonic fibroblasts (MEFs) with conditional CREPT deletion. Our results demonstrated that the loss of CREPT significantly impaired MYC-induced colony formation and cell proliferation, indicating that CREPT is essential for the malignant transformation of MEFs.

Perfluorooctane sulfonate (PFOS), a novel environmental pollutant, induces liver injury in mice by activating hepatocyte ferroptosis.

Objective: We investigated the toxicological mechanism by which perfluorooctane sulfonate (PFOS) induces liver injury via ferroptosis.

Methods: Primary mouse hepatocytes were treated with LD50 = 55 M PFOS. Their cytotoxicity was detected by CCK-8 and LDH assays, while JC-1 staining was used to identify their mitochondrial membrane potential.

Alginate/chitosan-based hemostatic microspheres loaded with doxorubicin liposomes for postoperative local drug delivery in solid tumor.

In clinical solid tumor treatment, intraoperative bleeding, compromised postoperative recovery, and increased non-specific toxicity from chemotherapy are always challenges. To address these limitations, we developed and well characterized novel alginate/chitosan-based hemostatic microspheres loaded with doxorubicin liposomes. The multifunctional microspheres exhibited optimal drug loading capacity and excellent drug encapsulation efficiency.

The Study of PIK3CA Hotspot Mutations and Co-Occurring with EGFR, KRAS, and TP53 Mutations in Non-Small Cell Lung Cancer.

Objective: PIK3CA-mutant non-small-cell lung cancer (NSCLC) is associated with other genetic mutations and may influence treatment strategies and clinical outcomes. We aimed to characterize PIK3CA mutations co-occurring with several major driver mutations using data from published cohorts and our medical center.

Materials And Methods: We analyzed NSCLC patients harboring PIK3CA mutations from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering (MSK) databases and retrospectively identified NSCLC patients with PIK3CA-mutants at a single medical center from our electronic records.

Exploration of novel human neutrophil elastase inhibitors from natural compounds: Virtual screening, in vitro, molecular dynamics simulation and in vivo study.

Background: Human neutrophil elastase (HNE) is an important contributor to lung diseases such as acute lung injury (ALI) or acute respiratory distress syndrome. Therefore, this study aimed to identify natural HNE inhibitors with anti-inflammatory activity through machine learning algorithms, in vitro assays, molecular dynamic simulation, and an in vivo ALI assay.

Methods: Based on the optimized Discovery Studio two-dimensional molecular descriptors, combined with different molecular fingerprints, six machine learning models were established using the Naïve Bayesian (NB) method to identify HNE inhibitors.

[Retracted] MicroRNA‑642a‑5p inhibits colon cancer cell migration and invasion by targeting collagen type I α1.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the cell invasion assay data shown in Fig. 6B on p. 940, and western blot data featured in Fig.

Crosstalk between circBMI1 and miR-338-5p/ID4 inhibits acute myeloid leukemia progression.

BMI1 polycomb ring finger proto-oncogene (BMI1) is involved in the pathogenesis of different cancers, including acute myeloid leukemia (AML). However, the role of the circular RNA of BMI1 (circBMI1) has not been studied. Our study aimed to investigate the role and mechanism of circBMI1 in AML.

High-throughput single-cell mass spectrometry enables metabolic network analysis by resolving phospholipid C[double bond, length as m-dash]C isomers.

Single-cell mass spectrometry (MS) is an essential technology for sensitive and multiplexed analysis of metabolites and lipids for cell phenotyping and pathway studies. However, the structural elucidation of lipids from single cells remains a challenge, especially in the high-throughput scenario. Technically, there is a contradiction between the inadequate sample amount ( a single cell, 0.

1-Ethoxycarbonyl-beta-carboline inhibits the M2 polarization of tumor-associated macrophages: A study based on network pharmacology and molecular docking analyses.

Aim: Through network pharmacology, molecular docking, molecular dynamics in combination with experimentation, we explored the mechanism whereby 1-ethoxycarbonyl-beta-carboline (EBC) regulates the M2 polarization of tumor-associated macrophages.

Methods: Network pharmacology was adopted for analyzing the targets and signaling pathways related to the M2 polarization of EBC-macrophages, small molecular-protein docking was employed to analyze the possibility of EBC bonding to related protein, and molecular dynamics was introduced to analyze the binding energy between EBC and HDAC2. The M2 polarization of RAW264.

Structure-based discovery of potent CARM1 inhibitors for colorectal cancer therapy.

Coactivator-associated arginine methyltransferase 1 (CARM1) plays an important role in cell proliferation and gene expression, and is highly expressed in a variety of tumor tissues. Guided by our previous reported structure of DCPR049_12, we focused on designing and evaluating selective CARM1 inhibitors, resulting in the identification of compound 11f as a promising lead candidate. Compound 11f displayed potent inhibition of CARM1 (IC = 9 nM).

Polystyrene microplastics exposure aggravates acute liver injury by promoting Kupffer cell pyroptosis.

Objective: To investigate the long-term effects of polystyrene (PS) exposure on acute liver injury.

Methods: The carbon tetrachloride-induced acute injury mouse model was subjected to long-term PS exposure. Pyroptosis was inhibited by knocking out Gsdmd in mice or treating with the Gsdmd inhibitor necrosulfonamide (NSA) to evaluate the effect of PS on liver injury.

Meniscal fibrocartilage regeneration inspired by meniscal maturational and regenerative process.

Meniscus is a complex and crucial fibrocartilaginous tissue within the knee joint. Meniscal regeneration remains to be a scientific and translational challenge. We clarified that mesenchymal stem cells (MSCs) participated in meniscal maturation and regeneration using MSC-tracing transgenic mice model.

Enhanced osteochondral repair with hyaline cartilage formation using an extracellular matrix-inspired natural scaffold.

Osteochondral defects pose a great challenge and a satisfactory strategy for their repair has yet to be identified. In particular, poor repair could result in the generation of fibrous cartilage and subchondral bone, causing the degeneration of osteochondral tissue and eventually leading to repair failure. Herein, taking inspiration from the chemical elements inherent in the natural extracellular matrix (ECM), we proposed a novel ECM-mimicking scaffold composed of natural polysaccharides and polypeptides for osteochondral repair.

3D Printing of Microenvironment-Specific Bioinspired and Exosome-Reinforced Hydrogel Scaffolds for Efficient Cartilage and Subchondral Bone Regeneration.

In clinical practice, repairing osteochondral defects presents a challenge due to the varying biological properties of articular cartilages and subchondral bones. Thus, elucidating how spatial microenvironment-specific biomimetic scaffolds can be used to simultaneously regenerate osteochondral tissue is an important research topic. Herein, a novel bioinspired double-network hydrogel scaffold produced via 3D printing with tissue-specific decellularized extracellular matrix (dECM) and human adipose mesenchymal stem cell (MSC)-derived exosomes is described.

Double-negative T cells regulate the progression of liver fibrosis through Th9 cells differentiation.

Our previous study found that double negative T cells (DNTs) could promote the NLRP3 activation through high expression of TNF-α, thereby leading to hepatic fibrosis progression. We focused on investigating the role and mechanism of DNTs in regulating the Th9 cells differentiation in liver fibrosis. In our results, among patients with liver fibrosis, the proportions of peripheral blood DNTs and Th9 cells were up-regulated and positively correlated.

Triterpene acid from alleviates inflammation in acute liver injury.

This study aimed to investigate the role and mechanism of Anctin A, the terpene component, in resisting liver injury. Network pharmacology analysis revealed that MAPK3 was the major action target of Antcin A. Furthermore, experimental research suggested that Antcin A suppressed mouse liver injury, reduced the inflammatory factor levels, and enhanced the anti-oxidative capacity.

Environmental toxin chlorpyrifos induces liver injury by activating P53-mediated ferroptosis via GSDMD-mtROS.

Aim: We investigate the mechanism whereby chlorpyrifos (CHI), an environmental toxin, causes liver injury by inducing ferroptosis in hepatocytes.

Methods: The toxic dose (LD50 = 50 μM) of CHI for inducing AML12 injury in normal mouse hepatocytes was determined, and the ferroptosis-related indices were measured, including the levels of SOD, MDA and GSH-Px, as well as the cellular content of iron ions. JC-1 and DCFH-DA assays were employed to detect the mtROS levels, the levels of mitochondrial proteins (GSDMD, NT-GSDMD), as well as the cellular levels of ferroptosis-related proteins (P53, GPX4, MDM2, SLC7A11).

Imidacloprid activates Kupffer cells pyroptosis to induce liver injury in mice via P2X7.

Aim: This work aimed to investigate the mechanism by which the environmental poison imidacloprid (IMI) induced liver injury.

Methods: First of all, IMI at the ED50 = 100 μM was added to treat mouse liver Kupffer cells, thereafter, the occurrence of pyroptosis was detected by flow cytometry (FCM), transmission electron microscope (TEM), immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), RT-QPCT and Western-Blot (WB) assay. Furthermore, P2X7 expression was knocked out in Kupffer cells, and cells were treated with the P2X7 inhibitor, so as to observe the pyroptosis level induced by IMI after P2X7 suppression.

TFAP4 promotes the progression of liver fibrosis through regulating double-negative T cell differentiation via OX40.

This work aimed to investigate the role of transcription factor TFAP4-OX40 in promoting the differentiation of double-negative T cells (DNTs). Through prediction and experimental analysis, it was discovered that TFAP4 was the transcription factor of OX40. Therefore, OX40 neutralizing antibody and TFAP4 overexpression transfection were adopted to investigate the role of TFAP4-OX40 in DNTs differentiation, and the effect of differentiated DNTs on hepatic stellate cell (HSC) activation.

Upregulated UBE4B expression correlates with poor prognosis and tumor immune infiltration in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a major human health concern. Increasing evidence has demonstrated that ubiquitin ligase E4B (UBE4B) may be involved in the occurrence and development of various human cancers and may affect prognosis. However, the specific role and mechanism of UBE4B in HCC is unclear.

Earlier and More Severe Cartilage Degeneration Occurs After Meniscal Tears in Juvenile Rabbits Compared with Adults.

Objective: To compare the severity of cartilage degeneration after meniscal tears between juvenile and adult rabbits.

Design: This study included 20 juvenile rabbits (2 weeks after birth) and 20 adult rabbits (6 months after birth). Meniscal tears were prepared in the anterior horn of medial menisci of right knees.