Tumor microenvironment targeting system for glioma treatment via fusion cell membrane coating nanotechnology.

The tumor microenvironment (TME), comprising cancer cells and stroma, plays a significant role in determining clinical outcomes, which makes targeting cancer cells in the TME an important area of research. One way in which cancer cells in the TME can be specifically targeted is by coating drug-encapsulated nanoparticles (NPs) with homotypic cancer cell membranes. However, incomplete targeting is inevitable for biomimetic nanoformulations coated with only cancer cell membranes because of the inherent heterogeneity of the TME. After observing the structural connection between glioma-associated stromal cells (GASCs) and glioma cells from a clinic, we designed a novel drug delivery system that targets the TME by coating polylactic-co-glycolic acid (PLGA) NPs with GASC-glioma cell fusion cell (SG cell) membranes. The resulting SGNPs inherited membrane proteins from both the glioma membrane and GASC membrane, significantly enhancing the tumor targeting efficiency compared to nanoformulations coated with cancer cell membranes alone. We further demonstrated that encapsulation of temozolomide (TMZ) improved the therapeutic efficacy of TMZ in both heterotopic and orthotopic glioma mouse models. Owing to its significant efficacy, our TME-targeting nanoplatform has potential for clinical applications in the treatment of various cancers.

Association between systemic inflammatory response syndrome and hematoma expansion in intracerebral hemorrhage.

BACKGROUND: Hematoma expansion (HE) is a relatively common complication after intracerebral hemorrhage. OBJECTIVES: To explore the association between systemic inflammatory response syndrome (SIRS) and HE in patients with intracerebral hemorrhage (ICH). MATERIAL AND METHODS: From June 2013 to October 2020, the sociodemographic data and clinical data of 780 ICH patients were collected. The logistic regression analysis with odd ratios (ORs) and 95% confidence intervals (95% CIs) was performed to analyze the risk factors for HE in patients with ICH. RESULTS: Hematoma expansion occurred in 151 (19.36%) patients with ICH. Significant differences were presented between SIRS and HE (OR = 2.549, 95% CI: [1.497; 4.342], p = 0.0006). After adjusting the covariates, a further analysis showed that the respiratory rate >20 beats/min (OR = 3.436, 95% CI: [1.981; 5.960], p < 0.0001), white blood cell (WBC) > 12×109/L or WBC ≤ 4×109/L (OR = 2.489, 95% CI: [1.494; 4.149], p = 0.0005) increased the risk for HE in ICH patients. Our study also found that the significant differences between HE and non-HE patients in proportion of patients with history of diabetes mellitus, basal ganglia hemorrhage, hypothalamus hemorrhage and fasting blood glucose (all p < 0.05) (OR = 2.076, 95% CI: [1.274; 3.381], p = 0.0034), basal ganglia hemorrhage (OR = 2.512, 95% CI: [1.496; 4.218], p = 0.0005), hypothalamus hemorrhage (OR = 2.121, 95% CI: [1.007; 4.466], p = 0.0479), high C-reactive protein (CRP) (OR = 1.013, 95% CI: [1.002; 1.024], p = 0.0184), and hyperglycemia (OR = 1.099, 95% CI: [1.026; 1.178], p = 0.0074) were associated with an increased risk of HE in ICH patients. CONCLUSIONS: The SIRS is closely associated with the risk of HE. Respiratory rate >20 beats/min and WBC count >12(109/L) or ≤4(109/L) increased the risk for HE in ICH patients. These findings can help to achieve the early prevention of HE and improve the prognosis of ICH patients.

Scoring Model to Predict Functional Outcome in Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

Background: Patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH), defined as World Federation of Neurosurgical Societies (WFNS) grades IV-V have high rates of disability and mortality. The objective of this study was to accurately prognosticate the outcomes of patients with poor-grade aSAH by developing a new scoring model. Methods: A total of 147 poor-grade aSAH patients in our center were enrolled. Risk variables identified by multivariate logistic regression analysis were used to devise a scoring model (total score, 0-9 points). The scores were estimated on the basis of ß coefficients. A cohort of 68 patients from another institute was used to validate the model. Results: Multivariate logistic regression analysis revealed that modified Fisher grade >2 [odds ratio [OR], 2.972; P = 0.034], age ≥65 years (OR, 3.534; P = 0.006), conservative treatment (OR, 5.078; P = 0.019), WFNS grade V (OR, 2.638; P = 0.029), delayed cerebral ischemia (OR, 3.170; P = 0.016), shunt-dependent hydrocephalus (OR, 3.202; P = 0.032), and cerebral herniation (OR, 7.337; P < 0.001) were significant predictors for poor prognosis [modified Rankin Scale [mRS] ≥3]. A scoring system was constructed by the integration of these factors and divided the poor-grade aSAH patients into three categories: low risk (0-1 points), intermediate risk (2-3 points), and high risk (4-9 points), with predicted risks of poor prognosis of 11, 52, and 87%, respectively (P < 0.001). The area under the curve in the derivation cohort was 0.844 (95% CI, 0.778-0.909). The AUC in the validation cohort was 0.831 (95% CI, 0.732-0.929). Conclusions: The new scoring model can improve prognostication and help decision-making for subsequent complementary treatment in patients with aSAH.

PTP1B inhibitor alleviates deleterious microglial activation and neuronal injury after ischemic stroke by modulating the ER stress-autophagy axis via PERK signaling in microglia.

Cerebral ischemia/reperfusion (IR) after ischemic stroke causes deleterious microglial activation. Protein tyrosine phosphatase 1B (PTP1B) exacerbates neuroinflammation, yet the effect of the inhibition on microglial activation and cerebral IR injury is unknown. A cerebral IR rat model was induced by middle cerebral artery occlusion (MCAO) and reperfusion. The PTP1B inhibitor, sc-222227, was administered intracerebroventricularly. Neurologic deficits, infarct volume, and brain water content were examined. An in vitro oxygen glucose deprivation/reoxygenation (OGD/R) model was established in primary microglia and BV-2 cells. Microglial activation/polarization, endoplasmic reticulum (ER) stress, autophagy, and apoptosis were detected using western blot, immunohistology, ELISA, and real-time PCR. Protein interaction was assessed by a proximity ligation assay. The results showed a significant increase in microglial PTP1B expression after IR injury. Sc-222227 attenuated IR-induced microglial activation, ER stress, and autophagy and promoted M2 polarization. Upon OGD/R, sc-222227 mitigated microglial activation by inhibiting ER stress-dependent autophagy, the effect of which was abolished by PERK activation, and PERK inhibition attenuated microglial activation. The PTP1B-phosphorylated PERK protein interaction was significantly increased after OGD/R, but decreased upon sc-222227 treatment. Finally, sc-222227 mitigated neuronal damage and neurologic deficits after IR injury. Treatment targeting microglial PTP1B might be a potential therapeutic strategy for ischemic stroke treatment.

Partially charged platinum on aminated and carboxylated SBA-15 as a catalyst for alkene hydrosilylation.

In this paper, we report the successful preparation of a novel bifunctional heterogeneous catalyst Pt δ+/SBA-APTE-SA with a partial positively charged Pt δ+ electronic structure via post-synthesis modification of (3-aminopropyl)triethoxysilane (APTE), succinic anhydride (SA) and platinum precursors. The resulting catalyst showed superior catalytic performance for the hydrosilylation of 1,1,1,3,5,5,5-heptamethyltrisiloxane (MDHM) with allyloxy polyethylene glycol (APEG) compared to a heterogeneous platinum catalyst. In addition, our catalyst was suitable for the hydrosilylation of other alkenes. Furthermore, the catalyst displayed sufficient stability after being reused five times without noticeable inactivation. In terms of cycle number and atomic utilization efficiency, it has potential applications as a green hydrosilylation method for industry.

Platinum on 2-aminoethanethiol functionalized MIL-101 as a catalyst for alkene hydrosilylation.

Hydrosilylation is one of the largest-scale applications for homogeneous catalysis and is widely used to enable the commercial manufacture of silicon products. In this paper, a bifunctional heterogeneous catalyst, Pt δ+/AET-MIL-101 (AET = 2-aminoethanethiol) with a partially positively charged Pt δ+ electronic structure is reported, which was successfully prepared using post-synthesis modification with AET and a platinum precursor. The catalysts were characterized using X-ray diffraction (XRD), nitrogen (N2) adsorption-desorption, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) techniques which showed that the synergy of AET-MIL-101 provides a good dispersion of Pt δ+ in the channels, which can efficiently catalyze the hydrosilylation reaction with almost complete conversion and produce a unique adduct. In addition, the synthetic heterogeneous catalyst Pt δ+/AET-MIL-101 achieves reasonable use of Pt in terms of number cycles and atomic utilization efficiency, indicating the potential to achieve a green hydrosilylation industry.