Carbon dots-mediated synthesis of gold nanodendrites with extended absorption into NIR-II window for in vivo photothermal therapy.

BACKGROUND: Photothermal therapy (PTT) in the second near-infrared (NIR-II) window has attracted extensive attention due to the benefits in high maximum permissible exposure and penetration depth. Current photothermal agents generally show a broadband absorption accompanied by a gradual attenuation of absorption in the NIR-II window, leading to poor effect of PTT. It remains a great challenge to gain photothermal agents with strong and characteristic absorption in NIR-II regions. To overcome this problem, based on carbon dots (CDs)-mediated growth strategy, we proposed a simple and feasible approach to prepare plasmonic gold nanodendrites (AuNDs) with NIR-II absorption to enhance the therapeutic effect of PTT. RESULTS: By rationally regulating the size and branch length of AuNDs, the AuNDs exhibited a broadband absorption from 300 to 1350 nm, with two characteristic absorption peaks located at 1077 and 1265 nm. The AuNDs demonstrated desired optical photothermal conversion efficiency (38.0%), which was further applied in NIR-II photoacoustic imaging (PAI) and PTT in human colon cancer cells (HCT 116)-tumor-bearing mice model. The tumor cells could be effectively eliminated in vivo under 1064 nm laser irradiation by the guidance of PAI. CONCLUSIONS: We reported a simple but powerful synthetic method to obtain the unique AuNDs with strong and characteristic absorption peaks in the NIR-II window. This study provides a promising solution to tuning the growth of nanoparticles for bioimaging and phototherapy in the NIR-II window.

Fermentation of Robinia pseudoacacia flower for improving the antioxidation: optimized conditions, active composition, mechanism, and biotransformation process.

Robinia pseudoacacia flower is a natural product with many biological activities, including antioxidation. To further develop its antioxidation, the extract was fermented by Aspergillus niger FFCC 3112 in the medium with carbon to nitrogen ratio of 1.4:1 and initial pH of 4.2 for 3.5 days to form the best antioxidant activity of the fermentation product by strain screening, single factor optimization, and response surface methodology. Further analysis, isolation and activity determination showed that a main chemical component, kaempferol-3-O-α-L-rhamnopyranosyl-(1→6)-ß-D-galactopyranosyl-7-O-α-L-rhamnopyranoside, in the extract was completely hydrolyzed to kaempferol-7-O-α-L-rhamnopyranoside and kaempferol with better antioxidant activity through biotransformation, which was the basis for improving the antioxidant activity of fermentation products. Moreover, the mechanism of antioxidant and the contribution of phenolic hydroxyl groups were investigated by density functional theory. The result indicated that the antioxidant capacity of kaempferol-7-O-α-L-rhamnopyranoside and kaempferol increased with the increase of solvent polarity. In high-polarity solvents, they mainly scavenge free radicals through single electron transfer followed by proton transfer.

Antrodia camphorata extract (ACE)-induced apoptosis is associated with BMP4 expression and p53-dependent ROS generation in human colon cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Antrodia camphorata (AC) is a rare functional fungus in Taiwan and is known as traditional Chinese medicine. It has been reported to inhibit proliferation and promote apoptosis in human cancer cells. AIM OF THE STUDY: To investigate the potential mechanism of apoptosis induced in colon cancer cells by Antrodia camphorata extract (ACE). MATERIALS AND METHODS: The MTT assay and crystal violet staining were used to determine relative cell viability in vitro at 24 and 48 h. The effects of ACE on apoptosis were determined by Hoechst 33342 staining and flow cytometric analysis following Annexin V-FITC/PI staining. The gene expression profile of HCT116 cells was assessed by the RNA sequencing system. In combination with RNA-seq data and qRT-PCR, Western blot analysis was used to evaluate expression of proteins. The intracellular ROS of HCT116 cells were determined using a DCFH-DA fluorescence probe. RESULTS: ACE significantly reduces cell viability in a dose-dependent manner and triggers apoptosis. To explore the underlying mechanism, we performed transcriptome analysis of ACE-treated colon cancer HCT116 cells. Bioinformatics analyses showed that ACE treatment is associated with pathways in cancer. We further used Cytoscape to analyze hub genes in this network. Among them, BMP4, which is associated with cancer cell death through regulation of the tumor suppressor p53, was significantly decreased at both mRNA and protein levels in ACE treatment groups. We found that cell death is reversible via inactivation or knockdown of p53 gene and reduction of reactive oxygen species (ROS) generation in response to ACE exposure, indicating that p53 plays an important role in ROS generation induced by ACE. Meanwhile, ROS scavenger NAC was used to verify that cell death is reversible via reduction of ROS. CONCLUSION: Our findings demonstrate that ACE has potential as an anticancer agent that induces apoptosis through BMP4 and p53-dependent response to ROS in human colon cancer.

Elevated Neurosteroids in the Lateral Thalamus Relieve Neuropathic Pain in Rats with Spared Nerve Injury.

Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of γ-aminobutyric acid A receptors (GABAARs), which play a vital role in pain modulation in the lateral thalamus, a main gate where somatosensory information enters the cerebral cortex. Using high-performance liquid chromatography/tandem mass spectrometry, we found increased levels of neurosteroids (pregnenolone, progesterone, deoxycorticosterone, allopregnanolone, and tetrahydrodeoxycorticosterone) in the chronic stage of neuropathic pain (28 days after spared nerve injury) in rats. The expression of the translocator protein TSPO, the upstream steroidogenesis rate-limiting enzyme, increased at the same time. In vivo stereotaxic microinjection of neurosteroids or the TSPO activator AC-5216 into the lateral thalamus (AP -3.0 mm, ML ±3.0 mm, DV 6.0 mm) alleviated the mechanical allodynia in neuropathic pain, while the TSPO inhibitor PK 11195 exacerbated it. The analgesic effects of AC-5216 and neurosteroids were significantly attenuated by the GABAAR antagonist bicuculline. These results suggested that elevated neurosteroids in the lateral thalamus play a protective role in the chronic stage of neuropathic pain.