NU7441, a selective inhibitor of DNA-PKcs, alleviates intracerebral hemorrhage injury with suppression of ferroptosis in brain.

Neuronal apoptosis, oxidative stress, and ferroptosis play a crucial role in the progression of secondary brain injury following intracerebral hemorrhage (ICH). Although studies have highlighted the important functions of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in various experimental models, its precise role and mechanism in ICH remain unclear. In this study, we investigated the effects of DNA-PKcs on N2A cells under a hemin-induced hemorrhagic state and a rat model of collagenase-induced ICH .

Polydopamine(PDA)-coated diselenide-bridged mesoporous silica-based nanoplatform for neuroprotection by reducing oxidative stress and targeting neuroinflammation in intracerebral hemorrhage.

Oxidative stress (OS) and neuroinflammation are critical pathological processes in secondary brain injury (SBI) after intracerebral hemorrhage(ICH), and their intimate interactions initiate and aggravate brain damage. Thus, targeting oxidative stress and neuroinflammation could be a promising therapeutic strategy for ICH treatment. Here, we report a high-performance platform using polydopamine (PDA)-coated diselenide bridged mesoporous silica nanoparticle (PDA-DSeMSN) as a smart ROS scavenger and ROS-responsive drug delivery system.

Fenton-like nanoparticles capable of HO self-supply and glutathione consumption for chemodynamic and chemotherapy of cancer.

Chemodynamic therapy (CDT) utilizing the Fenton reaction to convert hydrogen peroxide (HO) into cytotoxic hydroxyl radicals (˙OH) has recently drawn extensive interest in tumor treatment. However, the therapeutic efficiency of CDT often suffers from high concentrations of glutathione (GSH), insufficient endogenous HO and inefficient Fenton activity. Herein, a GSH-depleting and HO self-providing nanosystem that can efficiently load copper ions and doxorubicin (DOX) (MSN-Cu-DOX) to induce enhanced CDT and chemotherapy is proposed.

Breast phyllodes tumour with epithelioid feature predisposes to malignant transformation.

Aims: Phyllodes tumours (PTs) are relatively common fibroepithelial tumours comprising epithelial and stromal component. Usually, PTs show a spindle cell morphology with a fibroblast phenotype, while some tumour cells exhibit epithelioid morphological features and sarcomatoid transformation. However, the molecular characteristics of this morphology subset remain unclear.

Diselenide-Bridged Mesoporous Silica-Based Nanoplatform with a Triple ROS-Scavenging Effect for Intracerebral Hemorrhage Treatment.

Oxidative stress (OS) is a major mediator of secondary brain injury following intracerebral hemorrhage (ICH). Thus, antioxidant therapy is emerging as an attractive strategy to combat ICH. To achieve both reactive oxygen species (ROS) scavenging ability and on-demand drug release ability, we constructed a novel polydopamine (PDA)-coated diselenide-bridged mesoporous silica nanoparticle (DSeMSN) drug delivery system (PDA-DSeMSN).

Boosting Reactive Oxygen Species Generation with a Dual-Catalytic Nanomedicine for Enhanced Tumor Nanocatalytic Therapy.

Generating lethal reactive oxygen species (ROS) within tumors by nanocatalytic medicines is an advanced strategy for tumor-specific therapy in recent years. Nevertheless, the low yield of ROS restrains its therapeutic efficiency. Herein, a dual-catalytic nanomedicine based on tumor microenvironment (TME)-responsive liposomal nanosystem co-delivering CuO and dihydroartemisinin (DHA) (LIPSe@CuO&DHA) is developed to boost ROS generation against tumor.

A tetrasulfide bond-bridged mesoporous organosilica-based nanoplatform for triple-enhanced chemodynamic therapy combined with chemotherapy and HS therapy.

The high glutathione (GSH) concentration and insufficient HO content in tumor cells strongly constrict the efficacy of Fenton reaction-based chemodynamic therapy (CDT). Despite numerous efforts, it still remains a formidable challenge for achieving satisfactory efficacy using CDT alone. Herein, an intelligent tetrasulfide bond-bridged mesoporous organosilica-based nanoplatform that integrates GSH-depletion, HS generation, self-supplied HO, co-delivery of doxorubicin (DOX) and Fenton reagent Fe is presented for synergistic triple-enhanced CDT/chemotherapy/HS therapy.

Smart design of a therapeutic nanoplatform for mitochondria-targeted copper-depletion therapy combined with chemotherapy.

Mitochondria-targeted copper-depletion is emerging as an attractive strategy to combat cancer. However, existing copper molecular chelators are non-specific, toxic and ineffective. Here, it is reported that multifunctional nanoparticles (MSN-TPP/BNA-DPA) can not only target mitochondria to deprive copper ions to trigger copper-depletion therapy, but also serve as nanocarriers to deliver anticancer drugs for chemotherapy, which are engineered by conjugating a fluorophore 4-bromo-1,8-naphthalicanhydride (BNA), a copper-depriving moiety dimethylpyridinamine (DPA) and a mitochondrial targeting ligand triphenylphosphonium (TPP) on the surface of mesoporous silica nanoparticles (MSN).

Selective HDAC6 inhibitor TubA offers neuroprotection after intracerebral hemorrhage inhibiting neuronal apoptosis.

A large body of evidence has demonstrated that neuronal apoptosis is involved in the pathological process of secondary brain injury following intracerebral hemorrhage (ICH). Additionally, our previous studies determined that the inhibition of HDAC6 activity by tubacin or specific shRNA can attenuate neuronal apoptosis in an oxygen-glucose deprivation reperfusion model. However, whether the pharmacological inhibition of HDAC6-attenuated neuronal apoptosis in ICH remains unclear.

Enzyme-Triggered Size-Switchable Nanosystem for Deep Tumor Penetration and Hydrogen Therapy.

The poor penetration of nanocarriers within tumor dense extracellular matrices (ECM) greatly restricts the access of anticancer drugs to the deep tumor cells, resulting in low therapeutic efficacy. Moreover, the high toxicity of the traditional chemotherapeutics inevitably causes undesirable side effects. Herein, taking the advantages of biosafe H and small-sized nanoparticles in diffusion within tumor ECM, we develop a matrix metalloprotease 2 (MMP-2) responsive size-switchable nanoparticle (UAMSN@Gel-PEG) that is composed of ultrasmall amino-modified mesoporous silica nanoparticles (UAMSN) wrapped within a PEG-conjugated gelatin to deliver H to the deep part of tumors for effective gas therapy.

A pH-sensitive liposomal co-delivery of fingolimod and ammonia borane for treatment of intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is one of the most devastating types of stroke. This study aims to develop a new drug carrier with hematoma-specific response and high property. pH-sensitive liposomes (PSL) were developed.

Multichannel Ca Generator for Synergistic Tumor Therapy via Intracellular Ca Overload and Chemotherapy.

Ca overload has attracted an increasing attention due to its benefit of precise cancer therapy, but its efficacy is limited by the strong Ca excretion of cancer cells. Moreover, monotherapy of Ca overload usually fails to treat tumors satisfactorily. Herein, we develop a multifunctional nanosystem that could induce Ca overload by multipathway and simultaneously produce chemotherapy for synergistic tumor therapy.

Mesoporous peroxidase nanozyme for synergistic chemodynamic therapy and chemotherapy.

Peroxidase nanozyme, enabling decomposition of hydrogen peroxide (HO) into highly toxic hydroxyl radical (•OH), is an emerging technology for tumor treatment. However, limited by the low HO level in the tumor microenvironment, the standalone peroxidase nanozyme-mediated therapy usually fails to achieve desirable therapeutic outcomes. Herein, we presented a mesoporous nanozyme that not only had peroxidase-like activity but also could deliver anticancer drug for synergistic tumor therapy.

Electron Density Modulation of MoO/Ni to Produce Superior Hydrogen Evolution and Oxidation Activities.

Hydrogen evolution reaction (HER) and hydrogen oxidation reaction (HOR) have aroused great interest, but the high price of platinum group metals (PGMs) limits their development. The electronic reconstruction at the interface of a heterostructure is a promising strategy to enhance their catalytic performance. Here, MoO/Ni heterostructure was synthesized to provide effective HER in an alkaline electrolyte and exhibit excellent HOR performance.

Geranylgeranylacetone ameliorated ischemia/reperfusion induced-blood brain barrier breakdown through HSP70-dependent anti-apoptosis effect.

Background: Geranylgeranylacetone (GGA) has been recently reported to be centrally active after oral administration and protect against ischemic brain injury. This study was aimed to investigate the underlying mechanism of the protective effect of GGA.

Methods: In this study, transient middle cerebral artery occlusion (tMCAO) was established.

HSPB8 overexpression prevents disruption of blood-brain barrier after intracerebral hemorrhage in rats through Akt/GSK3β/β-catenin signaling pathway.

Blood brain barrier (BBB) disruption is a crucial factor contributing to secondary brain injury after intracerebral hemorrhage (ICH). Heat shock protein B8 (HSPB8) has been recently reported to confer neuroprotection against against ischaemic stroke through maintaining BBB integrity. However, the role of HSPB8 in ICH is still elusive.

L-3-n-butylphthalide attenuates inflammation response and brain edema in rat intracerebral hemorrhage model.

L-3-n-butylphthalide(NBP), a compound found in Linn seed extracts, has a therapeutic effect on acute ischemic stroke. The pathological inflammatory pathways and consequent brain edema in intracerebral hemorrhage (ICH) share some similar characteristics with ischemic stroke. We hypothesized that NBP has anti-inflammatory and therapeutic effects on rats with ICH.

HSPB8 over-expression prevents disruption of blood-brain barrier by promoting autophagic flux after cerebral ischemia/reperfusion injury.

Heat-shock protein B8 (HSPB8) has been recently reported to confer neuroprotection against ischemia/reperfusion (I/R)-induced cerebral injury in vivo and in vitro. However, the molecular mechanism is still elusive. This study focused on the effect of intracerebroventricular (i.