A Novel Oncolytic Virus Formulation Based on Mesenchymal Stem Cell-Derived Vesicles for Tumor Therapy.

Developing new drug delivery systems is crucial for enhancing the efficacy of oncolytic virus (OV) therapies in cancer treatment. In this study, mesenchymal stem cell (MSC)-derived vesicles and oncolytic viruses are exploited to construct a novel formulation. It has been hypothesized that vesicle-coated OVs could amplify cytotoxic effects through superior internalization by tumor cells.

Mesenchymal Stem Cell Membrane-Derived Composite System for Enhancing the Tumor Treatment Efficacy of Metal-Organic Framework Nanoparticles.

Mesenchymal stem cell (MSC) membrane-coated metal-organic frameworks (MOFs) represent an innovative approach to enhance the uptake and therapeutic efficacy of copper-based MOFs (Cu-MOFs) in tumor cells. By leveraging the natural homing abilities and biocompatibility of MSC membranes, Cu-MOFs can be effectively targeted to tumor sites, promoting increased cellular uptake. This coating not only facilitates superior internalization by cancer cells but also augments the therapeutic outcomes due to the enhanced delivery of copper ions.

Regulation of tumor antigens-Dependent immunotherapy via the hybrid M1 macrophage/tumor lysates Hydrogel.

Tumor treatment poses a significant obstacle in contemporary healthcare. Using components derived from a patient's own cellular and tissue materials to prepare hydrogels and other therapeutic systems has become a novel therapeutic approach, drawing considerable interest for their applicability in basic research on cancer immunotherapy. These hydrogels can engage with cellular components directly and offer a supportive scaffold, aiding in the normalization of tumor tissues.

Copper(II)-Based Nano-Regulator Correlates Cuproptosis Burst and Sequential Immunogenic Cell Death for Synergistic Cancer Immunotherapy.

Immunogenic cell death (ICD) of tumor cells serves as a crucial initial signal in the activation of anti-tumor immune responses, holding marked promise in the field of tumor immunotherapy. However, low immunogenicity tumors pose challenges in achieving complete induction of ICD, thereby limiting the response rates of immunotherapy in clinical patients. The emergence of cuproptosis as a new form of regulated cell death has presented a promising strategy for enhanced immunotherapy of low immunogenic tumors.

Genome-wide analysis of AP2/ERF transcription factors that regulate fruit development of Chinese prickly ash.

Background: AP2/ERF is a large family of plant transcription factor proteins that play essential roles in signal transduction, plant growth and development, and responses to various stresses. The AP2/ERF family has been identified and verified by functional analysis in various plants, but so far there has been no comprehensive study of these factors in Chinese prickly ash. Phylogenetic, motif, and functional analyses combined with transcriptome analysis of Chinese prickly ash fruits at different developmental stages (30, 60, and 90 days after anthesis) were conducted in this study.

Isorhamnetin alleviates ferroptosis-mediated colitis by activating the NRF2/HO-1 pathway and chelating iron.

Ferroptosis of intestinal epithelial cells (IECs) had been identified as a key factor in the development of ulcerative colitis (UC). Therefore, targeted inhibition of ferroptosis may provide a new strategy for the treatment of UC. Isorhamnetin (ISO) was an O-methylated flavonol with therapeutic effects on a variety of diseases, such as cardiovascular disease, neurological disorders and tumors.

Identification of a targeted ACSL4 inhibitor to treat ferroptosis-related diseases.

Ferroptosis is a form of iron-dependent, lipid peroxidation-driven regulatory cell death that has been implicated in the pathogenesis of multiple diseases, including organ injury, ischemia/reperfusion, and neurodegenerative diseases. However, inhibitors that directly and specifically target ferroptosis are not yet available. Here, we identify the compound AS-252424 (AS) as a potent ferroptosis inhibitor through kinase inhibitor library screening.

Tivantinib alleviates inflammatory diseases by directly targeting NLRP3.

NLRP3 inflammasome-mediated immune responses are involved in the pathogenesis of multiple inflammatory diseases, but few clinical drugs are identified that directly target the NLRP3 inflammasome to treat these diseases to date. Here, we show that the anticancer agent tivantinib is a selective inhibitor of NLRP3 and has a strong therapeutic effect on inflammasome-driven disease. Tivantinib specifically inhibits canonical and non-canonical NLRP3 inflammasome activation without affecting AIM2 and NLRC4 inflammasome activation.

Physiological and transcriptome analyses reveal the photosynthetic response to drought stress in drought-sensitive (Fengjiao) and drought-tolerant (Hanjiao) cultivars.

As an important economical plant, is widely cultivated in arid and semi-arid areas. The studies associated with photosynthesis under drought stress were widely carried out, but not yet in . Here, the photosynthesis of two cultivars (FJ, cv.

Widely targeted metabolomic profiling combined with transcriptome analysis provides new insights into amino acid biosynthesis in green and red pepper fruits.

The type and content of amino acids in pepper are important indicators to reflect its nutritional value, largely affecting the purchasing behavior of consumers. Understanding the biosynthesis of amino acids in pepper fruit is beneficial to the development of pepper functional food. Widely targeted metabolomics, transcriptome analysis, correlation analysis, weighted gene co-expression network analysis (WGCNA), and canonical correlation analysis (CCA) were used to evaluate the quality characteristics of green and red pepper amino acids.

Optimized Cationic Lipid-assisted Nanoparticle for Delivering CpG Oligodeoxynucleotides to Treat Hepatitis B Virus Infection.

Purpose: Hepatitis B virus (HBV) infection is such a global health problem that hundreds of millions of people are HBV carriers. Current anti-viral agents can inhibit HBV replication, but can hardly eradicate HBV. Cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODNs) are an adjuvant that can activate plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs) to induce therapeutic immunity for HBV eradication.

UPLC-MS/MS Profile Combined With RNA-Seq Reveals the Amino Acid Metabolism in Leaves Under Drought Stress.

leaves have a unique taste and incomparable nutritional value and hence are popular as a food item and traditional medicine in China. However, the studies on the metabolites in leaves are quite limited, especially for amino acids. Therefore, this study explored the amino acid component in leaves and also the accumulation mechanism under drought stress in two cultivars using the widely targeted metabolome combined with transcriptome analysis.

Genome-Wide Identification of the Gene Family in and Their Transcriptional Responses to Drought Stress.

NAC (NAM, ATAF1/2, and CUC2) transcription factors (TFs) are one of the largest plant-specific TF families and play a pivotal role in adaptation to abiotic stresses. The genome-wide analysis of NAC TFs is still absent in . Here, 109 ZbNAC proteins were identified from the genome and were classified into four groups with NAC proteins.

Bioorthogonal in situ assembly of nanomedicines as drug depots for extracellular drug delivery.

Developing precise nanomedicines to improve the transport of anticancer drugs into tumor tissue and to the final action site remains a critical challenge. Here, we present a bioorthogonal in situ assembly strategy for prolonged retention of nanomedicines within tumor areas to act as drug depots. After extravasating into the tumor site, the slightly acidic microenvironment induces the exposure of cysteine on the nanoparticle surface, which subsequently undergoes a bioorthogonal reaction with the 2-cyanobenzothiazole group of another neighboring nanoparticle, enabling the formation of micro-sized drug depots to enhance drug retention and enrichment.

Integrated LC-MS/MS and Transcriptome Sequencing Analysis Reveals the Mechanism of Color Formation During Prickly Ash Fruit Ripening.

Prickly ash peel is one of the eight major condiments in China and is widely used in cooking because of its unique fragrance and numbing taste. The color of prickly ash fruit is the most intuitive quality that affects consumer choice. However, the main components and key biosynthetic genes responsible for prickly ash fruit color have not yet been determined.

Integrated Analysis of Metabolome and Transcriptome Data for Uncovering Flavonoid Components of Maxim. Leaves Under Drought Stress.

Maxim. leaves (ZBLs) are rich in flavonoids and have become popular in nutrition, foods and medicine. However, the flavonoid components in ZBLs and the mechanism of flavonoid biosynthesis under drought stress have received little attention.

Tumor-Microenvironment-Activatable Polymer Nano-Immunomodulator for Precision Cancer Photoimmunotherapy.

Cancer nanomedicine combined with immunotherapy has become a promising strategy for treating cancer in terms of safety and potency; however, precise regulation of the activation of antitumor immunity remains challenging. Herein, a smart semiconducting polymer nano-immunomodulator (SPNI), which responds to the acidic tumor microenvironment (TME), for precision photodynamic immunotherapy of cancer, is reported. The SPNI is self-assembled by a near-infrared (NIR)-absorbing semiconducting polymer and an amphipathic polymer conjugated with a Toll-like receptor 7 (TLR7) agonist via an acid-labile linker.

Photo-Enhanced CRISPR/Cas9 System Enables Robust PD-L1 Gene Disruption in Cancer Cells and Cancer Stem-Like Cells for Efficient Cancer Immunotherapy.

Blocking immune checkpoint pathways with an antibody or small interfering RNA (siRNA) has become a promising method to reactivate antitumor responses for cancer treatment. However, both blockade strategies achieve only temporary inhibition of these immune checkpoints. Herein, a photoswitched CRISPR/Cas9 system for genomic disruption of the PD-L1 gene is developed to achieve permanent blockade of the PD-1/PD-L1 pathway; this system is constructed by using a photoactivated self-degradable polyethyleneimine derivative and the plasmid pX330/sgPD-L1 (expression of the Cas9 protein and single-guide RNA targeting PD-L1).

Dually regulating the proliferation and the immune microenvironment of melanoma via nanoparticle-delivered siRNA targeting onco-immunologic CD155.

Studies have shown that the simultaneous regulation of tumor cell proliferation and the suppressive tumor immune microenvironment (TIME) could achieve better therapeutic effects. However, the targets of the proliferation and the TIME are different, which greatly limits the development of cancer therapy. A recent study found CD155, a highly expressed poliovirus receptor in melanoma cells and melanoma-infiltrating macrophages, functions as both an oncogene and immune checkpoint.

An All-in-One Nanomedicine Consisting of CRISPR-Cas9 and an Autoantigen Peptide for Restoring Specific Immune Tolerance.

Nanotechnology has shown great promise in treating diverse diseases. However, developing nanomedicines that can cure autoimmune diseases without causing systemic immunosuppression is still quite challenging. Herein, we propose an all-in-one nanomedicine comprising an autoantigen peptide and CRISPR-Cas9 to restore specific immune tolerance by engineering dendritic cells (DCs) into a tolerogenic phenotype, which can expand autoantigen-specific regulatory T (Treg) cells.

Programmable Delivery of Immune Adjuvant to Tumor-Infiltrating Dendritic Cells for Cancer Immunotherapy.

Tumor-infiltrating dendritic cells (TIDCs) are mostly immature and immunosuppressive, usually mediating immune inhibition. The utilization of cytosine-guanine oligodeoxynucleotides (CpG ODNs) to stimulate the activation of TIDCs has been demonstrated to be effective for improving antitumor immunity. However, a series of biological barriers has limited the efficacy of previous nanocarriers for delivering CpG to TIDCs.

Linear Well-Defined Polyamines via Anionic Ring-Opening Polymerization of Activated Aziridines: From Mild Desulfonylation to Cell Transfection.

Linear polyethylenimine (L-PEI), a standard for nonviral gene delivery, is usually prepared by hydrolysis from poly(2-oxazoline)s. Lately, anionic polymerization of sulfonamide-activated aziridines had been reported as an alternative pathway toward well-defined L-PEI and linear polyamines. However, desulfonylation of the poly(sulfonyl aziridine)s typically relied on harsh conditions (acid, microwave) or used a toxic solvent (e.

Rational designs of in vivo CRISPR-Cas delivery systems.

The CRISPR-Cas system initiated a revolution in genome editing when it was, for the first time, demonstrated success in the mammalian cells. Today, scientists are able to readily edit genomes, regulate gene transcription, engineer posttranscriptional events, and image nucleic acids using CRISPR-Cas-based tools. However, to efficiently transport CRISPR-Cas into target tissues/cells remains challenging due to many extra- and intra-cellular barriers, therefore largely limiting the applications of CRISPR-based therapeutics in vivo.

Intratumor Performance and Therapeutic Efficacy of PAMAM Dendrimers Carried by Clustered Nanoparticles.

In recent years, small nanoparticles (NPs) with a diameter of less than 10 nm have aroused considerable interest in biomedical applications. However, their intratumor performance, as well as the antitumor efficacy, has not been well understood due to their size-dependent pharmacokinetics, which presents a formidable challenge for delivering a comparable amount of different small NPs to tumor tissues. Utilizing the multistage delivery strategy, we construct G3-, G5-, and G7-iCluster delivery systems by using poly(amidoamine) (PAMAM) dendrimers of different generations (G3-, G5-, and G7-PAMAM) as building blocks.

Enhanced Primary Tumor Penetration Facilitates Nanoparticle Draining into Lymph Nodes after Systemic Injection for Tumor Metastasis Inhibition.

Lymph nodes (LNs) are normally the primary site of tumor metastasis, and effective delivery of chemotherapeutics into LNs through systemic administration is critical for metastatic cancer treatment. Here, we uncovered that improved perfusion in a primary tumor facilitates nanoparticle translocation to LNs for inhibiting tumor metastasis. On the basis of our finding that an iCluster platform, which undergoes size reduction from ∼100 nm to ∼5 nm at the tumor site, markedly improved particle perfusion in the interstitium of the primary tumor, we further revealed in the current study that such tumor-specific size transition promoted particle intravasation into tumor lymphatics and migration into LNs.