Ganoderma Lucidum Polysaccharides Enhance the Abscopal Effect of Photothermal Therapy in Hepatoma-Bearing Mice Through Immunomodulatory, Anti-Proliferative, Pro-Apoptotic and Anti-Angiogenic.

Hepatocellular carcinoma is a malignant tumor with high morbidity and mortality, a highly effective treatment with low side effects and tolerance is needed. Photothermal immunotherapy is a promising treatment combining photothermal therapy (PTT) and immunotherapy. PTT induces the release of tumor-associated antigens by ablating tumor and Ganoderma lucidum polysaccharides (GLP) enhance the antitumor immunity. Results showed that Indocyanine Green (ICG) was successfully encapsulated into SF-Gel. ICG could convert light to heat and SF-Gel accelerates the photothermal effect in vitro and in vivo. PTT based on ICG/ICG-SF-Gel inhibited the growth of primary and distal tumors, GLP enhanced the inhibitory efficacy. ICG/ICG-SF-Gel-based PTT and GLP immunotherapy improved the survival time. ICG/ICG-SF-Gel-based PTT induces tumor necrosis and GLP enhanced the photothermal efficacy. ICG/ICG-SF-Gel-based PTT inhibited cell proliferation and angiogenesis, induced cell apoptosis, enhanced cellular immunity, and GLP enhanced these effects. In conclusion, GLP could enhance the abscopal effect of PTT in Hepatoma-bearing mice.

Intracerebroventricular Delivery of Recombinant NAMPT Deters Inflammation and Protects Against Cerebral Ischemia.

Our previous study indicated that nicotinamide phosphoribosyltransferase (NAMPT) is released from cells and might be an important extracellular neuroprotective factor in brain ischemia. Here, we tested whether NAMPT protects against ischemic brain injury when administered directly into the intracerebroventricular (ICV) compartment of the cranium. Recombinant NAMPT protein (2 µg) was delivered ICV in mice subjected to 45-min middle cerebral artery occlusion (MCAO), and the effects on infarct volume, sensorimotor function, microglia/macrophage polarization, neutrophil infiltration, and BBB integrity were analyzed. The results indicate that ICV administration of NAMPT significantly reduced infarct volume, retained its beneficial properties even when ICV administration was delayed by 6 h after MCAO, and improved neurological outcomes. NAMPT treatment inhibited pro-inflammatory microglia/macrophages, promoted microglia/macrophage polarization toward the anti-inflammatory phenotype, and reduced the infiltration of neutrophils into the perilesional area after brain ischemia. In vitro studies indicated that multiple pro-inflammatory microglial markers/cytokines were downregulated while multiple anti-inflammatory microglial markers/cytokines were induced in primary microglial cultures treated with NAMPT protein. NAMPT treatment also fortified the blood-brain barrier (BBB), as shown by reduced extravascular leakage of the small-molecule tracer Alexa Fluor 555 Cadaverine and larger-sized endogenous IgGs into brain parenchyma. Thus, NAMPT may protect against ischemic brain injury partly through a novel anti-inflammatory mechanism, which in turn maintains BBB integrity and reduces the infiltration of peripheral inflammatory cells. Taken together, these results provide validation of recombinant NAMPT delivery into the extracellular space as a potential neuroprotective strategy for stroke.

bFGF Protects Against Blood-Brain Barrier Damage Through Junction Protein Regulation via PI3K-Akt-Rac1 Pathway Following Traumatic Brain Injury.

Many traumatic brain injury (TBI) survivors sustain neurological disability and cognitive impairments due to the lack of defined therapies to reduce TBI-induced blood-brain barrier (BBB) breakdown. Exogenous basic fibroblast growth factor (bFGF) has been shown to have neuroprotective function in brain injury. The present study therefore investigates the beneficial effects of bFGF on the BBB after TBI and the underlying mechanisms. In this study, we demonstrate that bFGF reduces neurofunctional deficits and preserves BBB integrity in a mouse model of TBI. bFGF suppresses RhoA and upregulates tight junction proteins, thereby mitigating BBB breakdown. In vitro, bFGF exerts a protective effect on BBB by upregulating tight junction proteins claudin-5, occludin, zonula occludens-1, p120-catenin, and ß-catenin under oxygen glucose deprivation/reoxygenation (OGD) in human brain microvascular endothelial cells (HBMECs). Both the in vivo and in vitro effects are related to the activation of the downstream signaling pathway, PI3K/Akt/Rac-1. Inhibition of the PI3K/Akt or Rac-1 by specific inhibitors LY294002 or si-Rac-1, respectively, partially reduces the protective effect of bFGF on BBB integrity. Overall, our results indicate that the protective role of bFGF on BBB involves the regulation of tight junction proteins and RhoA in the TBI model and OGD-induced HBMECs injury, and that activation of the PI3K/Akt /Rac-1 signaling pathway underlies these effects.

FGFR4 and TGF-ß1 expression in hepatocellular carcinoma: correlation with clinicopathological features and prognosis.

OBJECTIVE: To investigate the expression and correlation of transforming growth factor-ß1 (TGF-ß1) and fibroblast growth factor receptor 4 (FGFR4) in human hepatocellular carcinoma (HCC) and the relationship with clinicopathological features and prognosis. MATERIALS AND METHODS: The expression of TGF-ß1 and FGFR4 in 126 HCC samples was detected immunohistochemically. Combined with clinical postoperative follow-up data, the expression of TGF-ß1 and FGFR4 in HCC and the relationship with the prognosis of patients were analyzed by statistically. RESULTS: The positive expression rate of TGF-ß1 was 84.1% (106/126) in tumors, and that in peritumoral liver tissues was 64.3% (81/126); the positive expression rate of FGFR4 in tumors was 74.6% (94/126) and that in peritumoral liver tissues was 57.1% (72/126). The expression of TGF-ß1 and FGFR4 in the carcinoma tissues was significantly higher than that in peritumoral liver tissues (p < 0.05). Intratumoral TGF-ß1 and FGFR4 expression was associated with TNM stage (p < 0.05). TGF-ß1 and FGFR4 expression levels didn't significantly correlate with other clinicopathological parameters, including age, sex, tumor size, serum AFP level, tumor differentiation, lymph node metastasis, etc. (p > 0.05). TGF-ß1 expression was positively correlated with FGFR4 expression (r = 0.595, p < 0.05). Patients with positive FGFR4 or TGF-ß1 expression had shorter overall survival compared with negative expression (p < 0.05). CONCLUSIONS: The expression of TGF-ß1 and FGFR4 could make synergy on the occurrence and progression of HCC, and may be used as prognosis indicators for HCC patients.

Cloud-point extraction and reversed-phase high-performance liquid chromatography for the determination of synthetic phenolic antioxidants in edible oils.

A cloud-point extraction (CPE) method using Triton X-114 (TX-114) nonionic surfactant was developed for the extraction and preconcentration of propyl gallate (PG), tertiary butyl hydroquinone (TBHQ), butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT) from edible oils. The optimum conditions of CPE were 2.5% (v/v) TX-114, 0.5% (w/v) NaCl and 40 min equilibration time at 50 °C. The surfactant-rich phase was then analyzed by reversed-phase high-performance liquid chromatography with ultraviolet detection at 280 nm, using a gradient mobile phase consisting of methanol and 1.5% (v/v) acetic acid. Under the studied conditions, 4 synthetic phenolic antioxidants (SPAs) were successfully separated within 24 min. The limits of detection (LOD) were 1.9 ng mL(-1) for PG, 11 ng mL(-1) for TBHQ, 2.3 ng mL(-1) for BHA, and 5.9 ng mL(-1) for BHT. Recoveries of the SPAs spiked into edible oil were in the range 81% to 88%. The CPE method was shown to be potentially useful for the preconcentration of the target analytes, with a preconcentration factor of 14. Moreover, the method is simple, has high sensitivity, consumes much less solvent than traditional methods, and is environment-friendly. Practical Application: The method established in this article uses less organic solvent to extract SPAs from edible oils; it is simple, highly sensitive and results in no pollution to the environment.