Bionic Power Play: Dual-Targeting MDMX/MDM2 to Reboot p53 to Beat Lung Adenocarcinoma's Immune Tricks.

Background And Aim: MDM2 and MDMX are key regulators of the tumor suppressor p53 and are implicated in immune escape mechanisms in lung adenocarcinoma. Overexpression of these proteins inhibits p53 activity, limiting the immune system's ability to recognize and clear tumor cells, contributing to resistance against immune checkpoint inhibitors (ICIs). This study introduces a novel bionic peptide nanodrug, E@MDP, designed to target both MDM2 and MDMX, reactivate p53, and enhance the effectiveness of PD-1 immune checkpoint therapy in lung cancer.

Garlic-Derived Allicin Attenuates Parkinson's Disease via PKA/p-CREB/BDNF/DAT Pathway Activation and Apoptotic Inhibition.

Allicin (ALC), a naturally occurring organosulfur compound derived from garlic (), exhibits potential neuroprotective properties. Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by degeneration of dopaminergic neurons and motor dysfunction. This study utilized bioinformatics and network pharmacology methods to predict the anti-PD mechanism of ALC and established in vivo and in vitro PD models using 6-hydroxydopamine (6-OHDA) for experimental verification.

Organoid scaffold materials: research and application.

In recent years, organoid research has witnessed remarkable progress, yet significant challenges remain in organoid construction. As fundamental architectural frameworks, organoid scaffolds play a pivotal role in facilitating three-dimensional tissue morphogenesis by delivering crucial biochemical and mechanical signals during organoid development. A systematic examination of scaffold functions in organoid culture systems, coupled with a critical assessment of different scaffold modalities, not only deepens our understanding of organoid biology and their microenvironment but also provides valuable insights for next-generation scaffold design.

DCAAA mitigates neuroinflammation and microglial pyroptosis in spinal cord injury by inhibiting PI3K/AKT/NF-κB and NLRP3/caspase-1/GSDMD signaling.

Spinal cord injury (SCI) is a highly disabling condition affecting the central nervous system (CNS). In the context of secondary SCI, microglial pyroptosis exerts a profound influence on neurological recovery. A novel lipophilic unsaturated fatty acid derivative from Isatis indigotica, DCAAA, has been synthesized and its structure and toxicity were evaluated.

Synergistic Antioxidant and Anti-Ferroptosis Therapy via BPNS-Encapsulated Thermoresponsive Chitosan Hydrogel for Spinal Cord Injury Regeneration.

: Spinal cord injury (SCI) is a devastating neurological condition with limited therapeutic options. Current clinical interventions predominantly rely on prolonged or high-dose pharmacological regimens, often causing systemic toxicity and adverse events. Although black phosphorus nanosheets (BPNSs) exhibit remarkable reactive oxygen species (ROS)-scavenging capacity to mitigate oxidative damage, their rapid degradation severely compromises their therapeutic efficacy.

Network Meta-Analysis of Stem Cell Therapies for Parkinson's Disease: Exploring the Optimal Strategy Based on Animal Models.

Stem cell therapy holds promise for Parkinson's disease (PD). To identify optimal stem cell regimens in PD mouse models and inform translational research, we conducted a network meta-analysis (NMA). Specifically, we systematically searched for studies on stem cell therapy in PD mouse models up to September 2024 in PubMed, Embase, Scopus, Web of Science, China National Knowledge Infrastructure, WANFANG, and VIP.

A genetic variant of the glutamate-cysteine ligase catalytic subunit is associated with susceptibility to ischemic stroke in the Chinese population.

Background: A pathogenetic factor of ischemic stroke (IS) is oxidative stress. As a rate-limiting enzyme constituent in the glutathione synthetic pathway, the glutamate-cysteine ligase catalytic subunit (GCLC) exerts a crucial effect on the redox homeostasis. Several studies have shown that variants of the GCLC gene are related to susceptibility to various diseases.

Immunological Safety Evaluation of Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells in Mice.

Mounting evidence indicates that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-exosomes) combine the advantages of hucMSC pluripotency with their nanoscale dimensions, enhancing their clinical potential through prolonged circulation half-life. Despite these promising characteristics, research on their immunological toxicity remains insufficient. This study focuses on the impact of hucMSC-exosomes on the general toxicity and immunopathological indicators.

Oxaliplatin-loaded natural killer cell-derived exosomes for a safe and efficient chemoimmunotherapy of colorectal cancer.

In recent years, the limited biocompatibility and serious side effects of oxaliplatin (L-OHP) have restricted its clinical application. Exosomes are biologically active vesicles with a double membrane structure secreted by almost all living cells. They transport biomolecules (e.

Mogroside V ameliorates astrocyte inflammation induced by cerebral ischemia through suppressing TLR4/TRADD pathway.

Inflammation and oxidative stress are pivotal factors in the onset and progression of secondary injury following cerebral ischemia-reperfusion (I/R). Mogroside V (MV), a primary active compound of Siraitia grosvenorii, exhibits significant anti-inflammatory and antioxidant properties. However, its specific effects in cerebral ischemia remain unclear.

Single-cell RNA sequencing revealed the immunophenotypic features of macrophages in cardiac transplants and uncovered Lgals9 promoted their polarization toward the M2b subtype.

Macrophages (MAC) play a crucial role in the immune response during allograft rejection in organ transplantation. Therefore, our study aimed to explore the genomic features of MAC in mouse heart transplants and use single-cell RNA sequencing to investigate Galectin-9 (Gal-9 and Lgals9), a lectin that can mediate the activation and differentiation of immune cells through ligand-receptor interactions, and the effects of its regulation in transplantation. We discovered a new subset of MAC called "Myoz2+ MAC," which specifically expressed genes related to myocardial contraction.

Less Is More: Donor Engineering of a Stable Molecular Dye for Bioimaging in the NIR-IIb Window.

Fluorescence molecular imaging aims to enhance clarity in the region of interest, particularly in the near-infrared IIb window (NIR-IIb, 1500-1700 nm). To achieve this, we developed a novel small-molecule dye, named , based on classic cyanine dyes (heptamethine or pentamethine is essential for wavelengths beyond 1000 nm). By reducing excessive polymethine to a single methine and disrupting symmetry to form an asymmetric donor-π-acceptor (D-π-A) architecture, we enhanced the donor's electron-donating capability, yielding emission at 1088 nm.

E3 ubiquitin ligase ITCH-mediated proteasomal degradation of WBP2 sensitizes breast cancer cells to chemotherapy through restraining AMOTL2/c-JUN axis.

Our study had demonstrated that WW domain-binding protein 2 (WBP2) conferred chemoresistance in breast cancer (BC). However, the underlying mechanism remains unclear. Herein, a decreased expression of itchy E3 ubiquitin protein ligase (ITCH) was observed in drug-resistant BC tissues which negatively regulated the expression of WBP2.

Drug repurposing opportunities for breast cancer and seven common subtypes.

Breast cancer is a substantial global health problem, and drug repurposing provides novel opportunities to address the urgent need for therapeutics. According to significant Mendelian randomization (MR) results, we identified 26 genes for overall breast cancer, 25 genes for ER+ breast cancer and 4 genes (CASP8, KCNN4, MYLK4, TNNT3) for ER- breast cancer. In order to explore the differences between 5 intrinsic subtypes, we found 29 actionable druggable genes for Luminal A breast cancer, 2 genes (IGF2 and TNNT3) for Luminal B breast cancer, 1 gene (FAAH) for Luminal B HER2 negative breast cancer, and 3 genes (CASP8, KCNN4, and TP53) for triple-negative breast cancer.

Preparation of curcumin-loaded chitosan/lecithin nanoparticles with increased anti-oxidant activity and in vivo bioavailability.

As a natural polyphenol, curcumin (Cur) has exhibited a range of bioactive properties, including anti-inflammatory, anti-oxidant, and anti-infection properties. However, the chemical instability and low water solubility of Cur hinder its wide application. Herein, Cur-loaded chitosan/lecithin nanoparticles (CCL NPs) were prepared by the electrostatic self-assembly method.

Treatment of Parkinson's disease model with human umbilical cord mesenchymal stem cell-derived exosomes loaded with BDNF.

Aims: Parkinson's disease (PD) is a common neurodegenerative disease that has received widespread attention; however, current clinical treatments can only relieve its symptoms, and do not effectively protect dopaminergic neurons. The purpose of the present study was to investigate the therapeutic effects of human umbilical cord mesenchymal stem cell-derived exosomes loaded with brain-derived neurotrophic factor (BDNF-EXO) on PD models and to explore the underlying mechanisms of these effects.

Main Methods: 6-Hydroxydopamine was used to establish in vivo and in vitro PD models.

CD5L up-regulates the TGF-β signaling pathway and promotes renal fibrosis.

Renal fibrosis is the common final pathway of progressive renal diseases, in which the macrophages play an important role. ELISA was used to detect CD5 antigen-like (CD5L) in serum samples from end-stage renal disease (ESRD), as well as in mice serum with unilateral ureteral occlusion (UUO). Recombinant CD5L was injected into UUO mice to assess renal injury, fibrosis, and macrophage infiltration.

C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury.

Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage. The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury. Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury, suggesting that this axis is a novel target and regulatory control point for treatment.

Accumulated inflammation and fibrosis participate in atrazine induced ovary toxicity in mice.

Atrazine is a widely used herbicide in agricultural production. Previous studies have shown that atrazine affects hormone secretion and oocyte maturation in female reproduction. However, the specific mechanism by which atrazine affects ovarian function remains unclear.

HucMSC extracellular vesicles increasing SATB 1 to activate the Wnt/β-catenin pathway in 6-OHDA-induced Parkinson's disease model.

Parkinson's disease (PD) is a degenerative disorder of the nervous system characterized by the loss of dopaminergic neurons and damage of neurons in the substantia nigra (SN) and striatum, resulting in impaired motor functions. This study aims to investigate how extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (HucMSC) regulate Special AT-rich sequence-binding protein-1 (SATB 1) and influence Wnt/β-catenin pathway and autophagy in PD model. The PD model was induced by damaging SH-SY5Y cells and mice using 6-OHDA.

Cuproptosis: Mechanism and Application in Lymphoma.

The cell death field has profited from the increasing attention of the scientific community and has been shown to lie at the very basis of cancer initiation and progression. Cuproptosis is a recently proposed method of cell death in 2022, and it is different from any previously reported method. The principle is that copper ions lead to aggregation and instability of intracellular proteins.

Identification of potential modulators for human GPD1 by docking-based virtual screening, molecular dynamics simulations, binding free energy calculations, and DeLA-drug analysis.

Cytosolic Glycerol-3-phosphate dehydrogenase 1 (GPD1, EC 1.1.1.

Identification of a ferroptosis-related prognostic signature and validation of ITGA6-AS1 in enhancing cell proliferation, migration and invasion in glioma.

Glioma is the most common malignant tumor of the adult central nervous system. In this study, we aimed to identify a novel model for predicting glioma prognosis and a potential therapeutic target. Here, lncRNAs related to prognosis and ferroptosis were analyzed and screened through R software and online websites.