Nanoparticle technologies offer a non-invasive means to deliver basic fibroblast growth factor (bFGF) for the treatment of spinal cord injury (SCI). However, the inability of bFGF to accumulate at the injury site and inefficient penetration across the blood-spinal cord barrier (BSCB) remain challenges. The present study describes a dual-targeting liposome (bFGF@Lip-Cp&Rp) with injury lesion targeting and BSCB-penetrating capability to deliver bFGF for SCI treatment. The CAQK peptide (Cp) with injury lesion targeting ability and R2KC peptide (Rp) with BSCB-penetrating capability were grafted onto the liposomes for a flexible and non-invasive drug delivery systems preparation. Results exhibit that the dual-targeted liposomes could significantly cross the BSCB and accumulate at the injury site. During the early stage of SCI, bFGF@Lip-Cp&Rp promotes repair of BSCB and facilitates M2-polarization of macrophages. Regular delivery of bFGF@Lip-Cp&Rp increase HUVECs tube formation and angiogenesis, ameliorate the microenvironment of lesion site, suppress the neuronal apoptosis and axonal atrophy in SCI rats. Importantly, continuous treatment of bFGF@Lip-Cp&Rp supports the restoration of limb motor function in SCI rats. In summary, this research implies that the injury site-targeting and BSCB-penetrating liposomes could be a promising therapeutic approach for the treatment of SCI.

UNASSIGNED: Inhibition of the programmed death ligand 1, programmed death 1 pathway has been successfully used for treatment of multiple advanced adult cancers. However, its use in pediatric osteosarcoma is still in its infancy. In this study, we investigated programmed death ligand 1 and other checkpoint molecules\' expression to determine the potential usefulness as targets for drug therapy.
UNASSIGNED: We incubated human wild-type osteosarcoma cells with incremental concentrations of doxorubicin to create a doxorubicin-resistant cell line. Matrigel in vitro invasion assays were used to compare invasiveness. Comparative programmed death ligand 1 expression was evaluated by Western blot assays. An immuno-oncology checkpoint protein panel was used to compare concentrations of 16 other checkpoint molecules. Chi-square tests and Wilcoxon rank-sum tests were used to determine significant differences.
UNASSIGNED: A doxorubicin-resistant cell line was successfully created and was significantly more invasive than wild-type cells (0.47 vs 0.07, P < .001). On Western blot assay, doxorubicin-resistant but not wild-type cells expressed programmed death ligand 1. Doxorubicin-resistant cells had significantly higher levels of T-cell immunoglobulin-3 and cluster of differentiation 86 and higher cluster of differentiation 27, cluster of differentiation 40, lymphocyte-activation gene-3, cluster of differentiation 80, programmed death ligand 1, programmed death ligand 2, and inducible T-cell costimulatory expression than wild-type cells. Both lines expressed B- and T-lymphocyte attenuator, cluster of differentiation 28, herpesvirus entry mediator, and programmed death 1. Herpesvirus entry mediator, cluster of differentiation 40, and programmed death ligand 2 were also present in the culture media of both cell lines.
UNASSIGNED: Doxorubicin-resistant osteosarcoma seems to express higher programmed death ligand 1 than nonresistant wild-type cells. Benchmarking checkpoint molecules may provide the basis for future studies that elucidate pathways of drug resistance and tumor metastasis, biomarkers for cancer prognosis or recurrence, and future targets for directed drug therapy.

UNASSIGNED: Hydrogen sulphide (H2S) has been established as a key member of the gasotransmitters family that recently showed a pivotal role in various pathological conditions including cancer.
UNASSIGNED: This study investigated the role of H2S in breast cancer (BC) pathogenesis, on BC immune recognition capacity and the consequence of targeting H2S using non-coding RNAs.
UNASSIGNED: Eighty BC patients have been recruited for the study. BC cell lines were cultured and transfected using validated oligonucleotide delivery system. Gene and protein expression analysis was performed using qRT-PCR, western blot and flow-cytometry. In-vitro analysis for BC hallmarks was performed using MTT, BrdU, Modified Boyden chamber, migration and colony forming assays. H2S and nitric oxide (NO) levels were measured spectrophotometrically. Primary natural killer cells (NK cells) and T cell isolation and chimeric antigen receptor transduction (CAR T cells) were performed using appropriate kits. NK and T cells cytotoxicity was measured. Finally, computational target prediction analysis and binding confirmation analyses were performed using different software and dual luciferase assay kit, respectively.
UNASSIGNED: The H2S synthesizing enzymes, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), exhibited elevated levels in the clinical samples that correlated with tumor proliferation index. Knock-down of CBS and CSE in the HER2+ BC and triple negative BC (TNBC) cells resulted in significant attenuation of BC malignancy. In addition to increased susceptibility of HER2+ BC and TNBC to the cytotoxic activity of HER2 targeting CAR T cells and NK cells, respectively. Transcriptomic and phosphoprotein analysis revealed that H2S signaling is mediated through Akt in MCF7, STAT3 in MDA-MB-231 and miR-155/ NOS2/NO signaling in both cell lines. Lastly, miR-4317 was found to function as an upstream regulator of CBS and CSE synergistically abrogates the malignancy of BC cells.
UNASSIGNED: These findings demonstrate the potential role of H2S signaling in BC pathogenesis and the potential of its targeting for disease mitigation.

Natural products generally fall into the biologically relevant chemical space and always possess novel biological activities, thus making them a rich source of lead compounds for new drug discovery. With the recent technological advances, natural product-based drug discovery is now reaching a new era. Natural products have also shown promise in epigenetic drug discovery, some of them have advanced into clinical trials or are presently being used in clinic. The histone lysine specific demethylase 1 (LSD1), an important class of histone demethylases, has fundamental roles in the development of various pathological conditions. Targeting LSD1 has been recognized as a promising therapeutic option for cancer treatment. Notably, some natural products with different chemotypes including protoberberine alkaloids, flavones, polyphenols, and cyclic peptides have shown effectiveness against LSD1. These natural products provide novel scaffolds for developing new LSD1 inhibitors. In this review, we mainly discuss the identification of natural LSD1 inhibitors, analysis of the co-crystal structures of LSD1/natural product complex, antitumor activity and their modes of action. We also briefly discuss the challenges faced in this field. We believe this review will provide a landscape of natural LSD1 inhibitors.