Stauntonia chinensis injection relieves neuropathic pain by increasing the expression of PSD-95 and reducing the proliferation of phagocytic microglia.

Neuroinflammation induced by engulfment of synapses by phagocytic microglia plays a crucial role in neuropathic pain. Stauntonia chinensis is extracted from Stauntonia chinensis DC, which has been used as a traditional Chinese medicine to control trigeminal neuralgia or sciatica. However, the specific anti-neuralgia mechanism of Stauntonia chinensis is unknown. In this study, the analgesic effect of Stauntonia chinensis injection (SCI) in mice with neuropathic pain and the possible mechanisms are explored. We find that a local injection of 0.1 mL Stauntonia chinensis for 14 days can considerably relieve mechanical hyperalgesia and thermal hyperalgesia in mice with sciatic chronic constriction injury (CCI). Immunofluorescence staining shows that SCI reduces neuroinflammation in the spinal cord of CCI mice. RNA sequencing reveals that the expression of postsynaptic density protein 95 (PSD-95), a postsynaptic scaffold protein, is downregulated in the spinal cord of CCI mice, but upregulated after SCI administration. Immunofluorescence experiments also demonstrate that SCI administration reverses microglia proliferation and PSD-95 downregulation in CCI mice. These data suggest that SCI relieves neuropathic pain by increasing the expression of PSD-95 and reducing the proliferation of phagocytic microglia.

Photodynamic Therapy Directed by Three-Photon Active Rigid Plane Organic Photosensitizer.

Multi-photon photosensitizers (PSs) could significantly improve the efficacy of photodynamic therapy due to the long-wavelength favorability for deeper tissue penetration and lower biological damage. However, most studies are limited to single-photon or two-photon PSs at a relatively short-wave excitation window. To overcome this barrier, we rationally design a series of rigid plane compounds with efficient reactive oxygen species (ROS) production in vitro under laser irradiation. Furthermore, the studies show that one of the compounds (U-TsO) could induce rapid multi-types of cell death under three-photon exposure, suggesting a promising clinical outcome in ex vivo 3D multicellular tumor spheroid. This work offers a novel strategy to construct functional materials with competitive multi-photon photodynamic therapy (PDT) outcome.

Revealing lipid droplets evolution at nanoscale under proteohormone stimulation by a BODIPY- hexylcarbazole derivative.

Lipid droplets (LDs) ultrastructure progression under proteohormone stimulation provide valuable clues for understanding conditions associated with obesity and diabetes. Current available LDs probes either alter intra-LDs environments or lack photo-resistance; thus, this research domain is poorly understood. In this work, a N-B-O type BODIPY- hexylcarbazole derivative named BoCz-Lip was rationally designed while achieving specific LDs live-cell targeting. BoCz-Lip showed minimal impact on cell viability as well as internal LDs' protein, triglyceride and cholesterol level. Along with its good photostability, it can be used to monitor LDs evolution under super-resolution nanoscopy. More importantly, we concluded how proteohormone could influence LDs ultrastructure, offering a better understanding for correlating diseases at the nanoscale.

Tuning cell behavior with nanoparticle shape.

We investigated how the shape of polymeric vesicles, made by the exact same material, impacts the replication activity and metabolic state of both cancer and non-cancer cell types. First, we isolated discrete geometrical structures (spheres and tubes) from a heterogeneous sample using density-gradient centrifugation. Then, we characterized the cellular internalization and the kinetics of uptake of both types of polymersomes in different cell types (either cancer or non-cancer cells). We also investigated the cellular metabolic response as a function of the shape of the structures internalized and discovered that tubular vesicles induce a significant decrease in the replication activity of cancer cells compared to spherical vesicles. We related this effect to the significant up-regulation of the tumor suppressor genes p21 and p53 with a concomitant activation of caspase 3/7. Finally, we demonstrated that combining the intrinsic shape-dependent effects of tubes with the delivery of doxorubicin significantly increases the cytotoxicity of the system. Our results illustrate how the geometrical conformation of nanoparticles could impact cell behavior and how this could be tuned to create novel drug delivery systems tailored to specific biomedical application.

Highly Hydrophilic, Two-photon Fluorescent Terpyridine Derivatives Containing Quaternary Ammonium for Specific Recognizing Ribosome RNA in Living Cells.

A two-photon fluorescent probe (J1) that selectively stains intracellular nucleolar RNA was screened from three water-soluble terpyridine derivatives (J1-J3) with quaternary ammonium groups. The photophysical properties of J1-J3 were systemically investigated both experimentally and theoretically, revealing that J1-J3 possess large Stokes shifts and the two-photon absorption action cross sections range from 38 to 97 GM in the near-infrared region. This indicates that J1 could specifically stain nucleoli by targeting the nucleolar rRNA from the recognition experiments in vitro, the two-photon imaging experiments, and the stimulated emission depletion in vivo. The mechanism of action in which J1 binds to the nucleolar rRNA was researched via both experiments and molecular modeling. The high binding selectivity of J1 to nucleolar RNA over cytosolic RNA made this probe a potential candidate to visualize rRNA probe in the living cells.

PPARγ activation rescues mitochondrial function from inhibition of complex I and loss of PINK1.

Parkinson's disease has long been associated with impaired mitochondrial complex I activity, while several gene defects associated with familial Parkinson's involve defects in mitochondrial function or 'quality control' pathways, causing an imbalance between mitochondrial biogenesis and removal of dysfunctional mitochondria by autophagy. Amongst these are mutations of the gene for PTEN-induced kinase 1 (PINK1) in which mitochondrial function is abnormal. Peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor and ligand-dependent transcription factor, regulates pathways of inflammation, lipid and carbohydrate metabolism, antioxidant defences and mitochondrial biogenesis. We have found that inhibition of complex I in human differentiated SHSY-5Y cells by the complex I inhibitor rotenone irreversibly decrease mitochondrial mass, membrane potential and oxygen consumption, while increasing free radical generation and autophagy. Similar changes are seen in PINK1 knockdown cells, in which potential, oxygen consumption and mitochondrial mass are all decreased. In both models, all these changes were reversed by pre-treatment of the cells with the PPARγ agonist, rosiglitazone, which increased mitochondrial biogenesis, increased oxygen consumption and suppressed free radical generation and autophagy. Thus, rosiglitazone is neuroprotective in two different models of mitochondrial dysfunction associated with Parkinson's disease through a direct impact on mitochondrial function.