Lipid nanoparticle-encapsulated lncRNA DLX6-AS1 knockdown ameliorates cerebral ischemic injury via the Nrf2/HO-1/NLRP3 axis.

Objective: Cerebral ischemia is a neurological disorder that leads to permanent disability. This research focuses on exploring the ameliorative effects of lipid nanoparticle (LNP)-encapsulated lncRNA DLX6-AS1 knockdown in cerebral ischemic injury via the Nrf2/HO-1/NLRP3 axis.

Methods: LNP-encapsulated lncRNA DLX6-AS1 was prepared.

Impacts of bisphenol A on growth and reproductive traits of submerged macrophyte Vallisneria natans.

Bisphenol A (BPA) is considered a contaminant of emerging concern and interferes with the normal activities of living organisms. The toxicity of BPA is evident in animals and terrestrial plants. However, the response of aquatic plants to low BPA concentrations is still unclear.

A MYC inhibitor selectively alters the MYC and MAX cistromes and modulates the epigenomic landscape to regulate target gene expression.

MYC regulates multiple gene programs, raising questions about the potential selectivity and downstream transcriptional consequences of MYC inhibitors as cancer therapeutics. Here, we examined the effect of a small-molecule MYC inhibitor, MYCi975, on the MYC/MAX cistromes, epigenome, transcriptome, and tumorigenesis. Integrating these data revealed three major classes of MYCi975-modulated gene targets: type 1 (down-regulated), type 2 (up-regulated), and type 3 (unaltered).

A Genome-Wide CRISPR Activation Screen Identifies PRRX2 as a Regulator of Enzalutamide Resistance in Prostate Cancer.

Unlabelled: Androgen receptor (AR) pathway inhibitors are the mainstay treatment for advanced prostate cancer, but resistance to therapy is common. Here, we used a CRISPR activation screen in metastatic castration-sensitive prostate cancer cells to identify genes that promote resistance to AR inhibitors. Activation of the TGFβ target gene paired-related homeobox2 (PRRX2) promoted enzalutamide resistance.

Dexmedetomidine exerts cerebral protective effects against cerebral ischemic injury by promoting the polarization of M2 microglia via the Nrf2/HO-1/NLRP3 pathway.

Introduction: Cerebral ischemic injury is associated with long-term disability. Dexmedetomidine (Dex) can exert neuroprotective effects on cerebral ischemic/reperfusion injury. The present study explored the mechanism of Dex in cerebral ischemic injury.

Biosynthesis and evaluation of a novel highly water-soluble quercetin glycoside derivative.

Quercetin () was converted into quercetin 7--succinyl glucoside () by used FJ18 as a solvent-resistant whole-cell biocatalyst. The structure of the new compound was confirmed by LC-MS analysis and NMR spectroscopy. The water-solubility of this novel quercetin 7--succinyl glucoside () was approximately 1000 times higher than that of native quercetin ().

Long non-coding RNA MIAT impairs neurological function in ischemic stroke via up-regulating microRNA-874-3p-targeted IL1B.

Objective: Long non-coding RNAs (lncRNAs) have diagnostic and therapeutic values in the setting of ischemic stroke (IS). Here, we evaluated the value of myocardial infarction-associated transcript (MIAT) in IS with the involvement of microRNA (miR)-874-3p/interleukin (IL) 1B.

Methods: MIAT, miR-874-3p and IL1B levels in serum of patients with IS were measured.

Activated ALK Cooperates with N-Myc via Wnt/β-Catenin Signaling to Induce Neuroendocrine Prostate Cancer.

Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer with poor prognosis, and there is a critical need for novel therapeutic approaches. NEPC is associated with molecular perturbation of several pathways, including amplification of . Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase involved in the pathogenesis of neuroblastoma and other malignancies where it cooperates with N-Myc.

Turning Up the Heat on MYC: Progress in Small-Molecule Inhibitors.

MYC is a highly validated oncogenic transcription factor and cancer target. However, the disordered nature of this protein has made it a challenging target, with no clinical stage, direct small-molecule MYC inhibitors available. Recent work leveraging a large chemical library and a rapid screen has expanded the chemotypes of direct small-molecule inhibitors (MYCi).

Small-Molecule MYC Inhibitors Suppress Tumor Growth and Enhance Immunotherapy.

Small molecules that directly target MYC and are also well tolerated in vivo will provide invaluable chemical probes and potential anti-cancer therapeutic agents. We developed a series of small-molecule MYC inhibitors that engage MYC inside cells, disrupt MYC/MAX dimers, and impair MYC-driven gene expression. The compounds enhance MYC phosphorylation on threonine-58, consequently increasing proteasome-mediated MYC degradation.

EPHB4 inhibition activates ER stress to promote immunogenic cell death of prostate cancer cells.

The EPHB4 receptor is implicated in the development of several epithelial tumors and is a promising therapeutic target, including in prostate tumors in which EPHB4 is overexpressed and promotes tumorigenicity. Here, we show that high expression of EPHB4 correlated with poor survival in prostate cancer patients and EPHB4 inhibition induced cell death in both hormone sensitive and castration-resistant prostate cancer cells. EPHB4 inhibition reduced expression of the glucose transporter, GLUT3, impaired glucose uptake, and reduced cellular ATP levels.

Synthesis of novel functional ionic liquids and their application in biomass.

A series of dicationic ionic liquids (ILs) including [PF][(PYR)C(MIM)][Cl], [PF][(PYR)C(PYR)][Cl], [PF][(PYR)C(MIM)][Cl], and [PF][(PYR)C(PYR)][Cl], and monocationic ILs including [(PYR)CCl][PF], [(PYR)CCl][PF], [(MIM)CCOOH][PF] and [(PYR)CCOOH][PF] were synthesized. Their thermal stability and melting points were determined. Their solubility with organic solvents and the miscibility with water were investigated.

Exosome-Transmitted and Promote Proteasome Inhibitor Resistance in Multiple Myeloma.

Purpose: How exosomal RNAs released within the bone marrow microenvironment affect proteasome inhibitors' (PI) sensitivity of multiple myeloma is currently unknown. This study aims to evaluate which exosomal RNAs are involved and by which molecular mechanisms they exert this function. Exosomes were characterized by dynamic light scattering, transmission electron microscopy, and Western blot analysis.

HOXC10 Regulates Osteogenesis of Mesenchymal Stromal Cells Through Interaction with Its Natural Antisense Transcript lncHOXC-AS3.

The characteristics of mesenchymal stromal cells (MSCs) which derived from multiple myeloma (MM) patients are typically impaired in osteogenic differentiation. However, the underlying molecular mechanisms need to be further investigated. lncRNAs are emerging as critical regulation molecules in oncogenic pathways.

The BET Bromodomain Inhibitor OTX015 Synergizes with Targeted Agents in Multiple Myeloma.

Treatment failure remains a main challenge in the management of high-risk multiple myeloma (MM) even with the expanding repertoire of new drugs. Combinatorial therapy is considered an encouraging strategy that can overcome the compensatory mechanisms and undesirable off-target effects that limit the benefits of many prospective agents. Preliminary results of a current phase I trial have indicated that the new BET bromodomain inhibitor OTX015 has favorable activity and tolerability.

Screening of potential IL-tolerant cellulases and their efficient saccharification of IL-pretreated lignocelluloses.

Lignocellulosic biomass as one of the most abundant and renewable resources has great potential for biofuel production. The complete conversion of biomass to biofuel is achieved through the effective pretreatment process and the following enzyme saccharification. Ionic liquids (ILs) are considered as a green solvent for lignocellulose pretreatment.

Potent Activity of the Bromodomain Inhibitor OTX015 in Multiple Myeloma.

Several studies demonstrate that the bromodomain inhibitor OTX015 has an antitumor activity in cancers. However, translation of these data to molecules suitable for clinical development has yet to be accomplished in multiple myeloma (MM). Here, we identified genes and biologic processes that substantiated the antimyeloma activity of OTX015 with global transcriptomics.

Exosome-mediated transfer of lncRUNX2-AS1 from multiple myeloma cells to MSCs contributes to osteogenesis.

Multiple myeloma (MM) is characterized by the decreased osteogenic potential of mesenchymal stem cells (MSCs). Communication between cancer cells and cancer stromal cells is a driving factor in tumor progression. Understanding the myeloma-stroma interactions is critical to the development of effective strategies that can reverse bone diseases.

Pathway-structured predictive modeling for multi-level drug response in multiple myeloma.

Motivation: Molecular analyses suggest that myeloma is composed of distinct sub-types that have different molecular pathologies and various response rates to certain treatments. Drug responses in multiple myeloma (MM) are usually recorded as a multi-level ordinal outcome. One of the goals of drug response studies is to predict which response category any patients belong to with high probability based on their clinical and molecular features.

Predicting multi-level drug response with gene expression profile in multiple myeloma using hierarchical ordinal regression.

Background: Multiple myeloma (MM), like other cancers, is caused by the accumulation of genetic abnormalities. Heterogeneity exists in the patients' response to treatments, for example, bortezomib. This urges efforts to identify biomarkers from numerous molecular features and build predictive models for identifying patients that can benefit from a certain treatment scheme.

Anaplastic Lymphoma Kinase Mutation ( F1174C) in Small Cell Carcinoma of the Prostate and Molecular Response to Alectinib.

Small cell carcinoma of the prostate (SCCP) is an aggressive disease that can arise or by transdifferentiation from prostate adenocarcinoma. Alterations in anaplastic lymphoma kinase () gene are involved in neuroblastoma, lung cancer, and other malignancies, but its role in SCCP has not been documented. We describe a patient with refractory SCCP with F1174C-activating mutation who obtained clinical benefit from treatment with ALK inhibitor.

TIMP-2 modulates cancer cell transcriptional profile and enhances E-cadherin/beta-catenin complex expression in A549 lung cancer cells.

Tissue Inhibitor of Metalloproteinase 2 (TIMP-2) plays an essential role in regulating matrix remodeling, cell growth, differentiation, angiogenesis and apoptosis in vitro and in vivo. We have recently shown that TIMP-2-mediated inhibition of tumor growth is independent of matrix metalloproteinase-mediated mechanisms, and is a consequence of modulating both the tumor cells and the tumor microenvironment. In the current study we aim to identify the molecular pathways associated with these effects.