Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a member of C-type lectin-like receptor family.It can recognize many ligands and is the main receptor of oxidized low-density lipoprotein for inducing vascular endothelial dysfunction.Early studies focused on the role of LOX-1 in atherosclerosis and diabetes mellitus.Recent studies have shown that LOX-1 is closely associated with ischemic stroke.This article reviews the biological characteristics of LOX-1 and its association with ischemic stroke.

UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a key role in detoxification of many potentially harmful compounds and drugs. UGT1A1 inhibition may bring risks of drug-drug interactions (DDIs), hyperbilirubinemia and drug-induced liver injury. This study aimed to investigate and compare the inhibitory effects of icotinib and erlotinib against UGT1A1, as well as to evaluate their potential DDI risksUGT1A1 inhibition. The results demonstrated that both icotinib and erlotinib are UGT1A1 inhibitors, but the inhibitory effect of icotinib on UGT1A1 is weaker than that of erlotinib. The ICvalues of icotinib and erlotinib against UGT1A1-mediated NCHN--glucuronidation in human liver microsomes (HLMs) were 5.15 and 0.68 μmol/L, respectively. Inhibition kinetic analyses demonstrated that both icotinib and erlotinib were non-competitive inhibitors against UGT1A1-mediated glucuronidation of NCHN in HLMs, with thevalues of 8.55 and 1.23 μmol/L, respectively. Furthermore, their potential DDI risksUGT1A1 inhibition were quantitatively predicted by the ratio of the areas under the concentration-time curve (AUC) of NCHN. These findings are helpful for the medicinal chemists to design and develop next generation tyrosine kinase inhibitors with improved safety, as well as to guide reasonable applications of icotinib and erlotinib in clinic, especially for avoiding their potential DDI risksUGT1A1 inhibition.

To understand how the nervous system develops from a small pool of progenitors during early embryonic development, it is fundamentally important to identify the diversity of neuronal subtypes, decode the origin of neuronal diversity, and uncover the principles governing neuronal specification across different regions. Recent single-cell analyses have systematically identified neuronal diversity at unprecedented scale and speed, leaving the deconstruction of spatiotemporal mechanisms for generating neuronal diversity an imperative and paramount challenge. In this review, we highlight three distinct strategies deployed by neural progenitors to produce diverse neuronal subtypes, including predetermined, stochastic, and cascade diversifying models, and elaborate how these strategies are implemented in distinct regions such as the neocortex, spinal cord, retina, and hypothalamus. Importantly, the identity of neural progenitors is defined by their spatial position and temporal patterning factors, and each type of progenitor cell gives rise to distinguishable cohorts of neuronal subtypes. Microenvironmental cues, spontaneous activity, and connectional pattern further reshape and diversify the fate of unspecialized neurons in particular regions. The illumination of how neuronal diversity is generated will pave the way for producing specific brain organoids to model human disease and desired neuronal subtypes for cell therapy, as well as understanding the organization of functional neural circuits and the evolution of the nervous system.
Humans ; Neural Stem Cells/physiology* ; Neurons/physiology* ; Brain ; Spinal Cord ; Embryonic Development ; Cell Differentiation/physiology*

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Although different types of drugs are available for postmenopausal osteoporosis, the limitations of the current therapies including drug resistances and adverse effects require identification of novel anti-osteoporosis agents. Here, we defined that norlichexanthone (NOR), a natural product, is a ligand of estrogen receptor-alpha (ER

Objective: To investigate the effects of interferon inducible protein 16 (IFI16), a cytosolic DNA sensor, on the expression of human T-cell leukemia virus type 1 (HTLV-1) proteins and pro-inflammatory cytokines in adult HTLV-1-positive T cells. Methods: IFI16 expression in different HTLV-1-positive T cell lines was detected by immunoblot assay. Specific siRNA targeting the IFI16 gene was constructed and the gene silencing efficiency was detected by immunoblot assay. Expression of HTLV-1 Tax protein at mRNA and protein levels was respectively detected by real-time PCR and immunoblot assay after knocking down the expression of IFI16 in HTLV-1-positive T cells with siRNA. Expression of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, Tax and Env were detected by real-time PCR. Results: Compared with the HTLV-1-negative T cell line Jurkat, IFI16 expression was enhanced in the HTLV-1-positive T cell lines MT2, MT4 and C8166. Tax expression was increased, while that of IFN-α, IFN-γ and TNF-α was decreased in MT2 and MT4 cells after silencing the expression of IFI16 with siRNA. Conclusions IFI16 expression was increased in HTLV-1-positive MT2 and MT4 cells. Meanwhile, IFI16 promoted the production of interferon and pro-inflammatory cytokines and inhibited the expression of HTLV-1 proteins.

Maintaining the stemness of the transplanted stem cell spheroids in an inflammatory microenvironment is challenging but important in regenerative medicine. Direct delivery of stem cells to repair periodontal defects may yield suboptimal effects due to the complexity of the periodontal inflammatory environment. Herein, stem cell spheroid is encapsulated by interfacial assembly of metal-phenolic network (MPN) nanofilm to form a stem cell microsphere capsule. Specifically, periodontal ligament stem cells (PDLSCs) spheroid was coated with Fe^III/tannic acid coordination network to obtain spheroid@[Fe^III-TA] microcapsules. The formed biodegradable MPN biointerface acted as a cytoprotective barrier and exhibited antioxidative, antibacterial and anti-inflammatory activities, effectively remodeling the inflammatory microenvironment and maintaining the stemness of PDLSCs. The stem cell microencapsulation proposed in this study can be applied to multiple stem cells with various functional metal ion/polyphenol coordination, providing a simple yet efficient delivery strategy for stem cell stemness maintenance in an inflammatory environment toward a better therapeutic outcome.
Anti-Bacterial Agents/pharmacology* ; Capsules/pharmacology* ; Cell Differentiation ; Cell Encapsulation ; Cells, Cultured ; Ferric Compounds/pharmacology* ; Osteogenesis/physiology* ; Periodontal Ligament ; Polyphenols/pharmacology* ; Stem Cells ; Tannins/pharmacology*