The mechanism and experimental verification of Ixeris sonchifolia promoting apoptosis of hepatocellular carcinoma based on network pharmacology: Ixeris sonchifolia Induces Hepatocellular Carcinoma Apoptosis via the PI3K/AKT Pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ixeris sonchifolia alias Kudiezi, it was named Ixeris sonchifolia (Bunge) Hance, a synonym for Crepidiastrum sonchifolium (Bunge) Pak & Kawano in the https://www.iplant.cn/. And it was first published in J. Linn. Soc., Bot. 13: 108 (1873), which was named Ixeris sonchifolia (Maxim.) Hance in the MPNS (http://mpns.kew.org). As a widely distributed medicinal and edible wild plant, it possesses unique bitter-cold characteristics and constituents with various pharmacological activities. Its main antitumor substances, same as artemisinin and paclitaxel, are classified as terpenoids and have become research foci in recent years. However, its specific biological activity and role in antitumor treatment remain largely unclear. AIM OF THE STUDY: This study aimed to elucidate the molecular targets and potential mechanisms of hepatocellular carcinoma apoptosis induced by Ixeris sonchifolia. MATERIALS AND METHODS: We used network pharmacology methods to analyze and screen the active ingredients and possible underlying mechanisms of Ixeris sonchifolia in treating liver cancer and employed integrative time- and dose-dependent toxicity, transcriptomics, and molecular biology approaches to comprehensively verify the function of Ixeris sonchifolia extract (IsE) in human hepatoblastoma cell (HepG2) apoptosis and its potential mechanism. RESULTS: A total of 169 common targets were screened by network pharmacology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that IsE inhibited HepG2 cell activity in a time- and dose-dependent manner. Western blot analysis confirmed that IsE promoted HepG2 cell apoptosis by inhibiting the PI3K/AKT signaling pathway and that the PI3K/AKT inhibitor LY294002 also substantially enhanced IsE-induced apoptosis. The PI3K/AKT signaling pathway exhibited significant differences compared to that in the control group. CONCLUSION: Combining network pharmacology with experimental verification, IsE inhibited mitochondrial function and the PI3K/AKT pathway while inducing hepatoma cell apoptosis. IsE may have promising potential for liver cancer treatment and chemoprevention.

In Situ Seed-Mediated Growth of Polymer-Grafted Gold Nanoparticles.

We report a facile yet general in situ seed-mediated method for the synthesis of polymer-grafted gold nanoparticles with narrow size distributions (<10%), accurately tunable sizes, and excellent colloidal stability. This method can be extended to a broad range of types and molecular weights of polymer ligands. Nanoparticles with different shapes can also be prepared by using preformed shaped nanoparticles directly as the seeds.

Chiral Plasmonic Nanochains via the Self-Assembly of Gold Nanorods and Helical Glutathione Oligomers Facilitated by Cetyltrimethylammonium Bromide Micelles.

Gold nanorods are excellent anisotropic building blocks for plasmonic chiral nanostructures. The near-infrared plasmonic band of nanorods makes them highly desirable for biomedical applications such as chiral bioimaging and sensing, in which a strong circular dichroism (CD) signal is required. Chiral assemblies of gold nanorods induced by self-associating peptides are especially attractive for this purpose as they exhibit plasmonic-enhanced chiroptical activity. Here, we showed that the presence of cetyltrimethylammonium bromide (CTAB) micelles in a gold nanorod solution promoted the self-association of l-/d-glutathione (GSH) and significantly enhanced the chirality of the resulting plasmonic nanochains. Chiroptical signals for the ensemble in the presence of CTAB micelles were 20 times greater than those obtained below the critical micelle concentration of CTAB. The strong optical activity was attributed to the formation of helical GSH oligomers in the hydrophobic core of the CTAB micelles. The helical GSH oligomers led the nanorods to assemble in a chiral, end-to-end crossed fashion. The CD signal intensities were also proportional to the fraction of nanorods in the nanochains. In addition, finite-difference time-domain simulations agreed well with the experimental extinction and CD spectra. Our work demonstrated a substantial effect from the CTAB micelles on gold nanoparticle assemblies induced by biomolecules and showed the importance of size matching between the inorganic nanobuilding blocks and the chiral molecular templates (i.e., the GSH oligomers in the present case) in order to attain strong chiroptical activities.

Endoscope-guided interstitial intensity-modulated brachytherapy and intracavitary brachytherapy as boost radiation for primary early T stage nasopharyngeal carcinoma.

BACKGROUND: Intracavitary brachytherapy (ICBT) is usually applied as boost radiotherapy for superficial residual of nasopharyngeal carcinoma (NPC) after primary extern-beam radiptherapy (ERT). Here, we evaluated the outcome of endoscope-guided interstitial intensity-modulated brachytherapy (IMBT) boost radiation for deep-seated residual NPC. METHODOLOGY/PRINCIPAL FINDINGS: Two hundred and thirteen patients with residual NPC who were salvaged with brachytherapy boost radiation during 2005-2009 were analyzed retrospectively. Among these patients, 171 patients had superficial residual NPC (≤1 cm below the nasopharyngeal epithelium) were treated with ICBT boost radiation, and interstitial IMBT boost radiation was delivered to 42 patients with deep-seated residual NPC (>1 cm below the nasopharyngeal epithelium). We found that IMBT boost subgroup had a higher ratio of T2b (81.0% VS 34.5%, P<0.001) and stage II (90.5% VS 61.4%, P = 0.001) than that of ICBT boost subgroup. The dosage of external-beam radiotherapy in the nasopharyngeal (63.0±3.8 VS 62.6±4.3 Gray (Gy), P = 0.67) and regional lymph nodes (55.8±5.0 VS 57.5±5.7 Gy, P = 0.11) was comparable in both groups. For brachytherapy, IMBT subgroup had a lower boost radiation dosage than ICBT subgroup (11.0±2.9 VS 14.8±3.2 Gy, P<0.01). Though the IMBT group had deeper residual tumors and received lower boost radiation dosages, both subgroups had the similar 5-year actuarial overall survival rate (IMBT VS ICBT group: 96.8% VS 93.6%, P = 0.87), progression-free survival rate (92.4% VS 86.5%, P = 0.41) and distant metastasis-free survival rate (94.9% VS 92.7%, P = 0.64). Moreover, IMBT boost radiation subgroup had a similar local (97.4% VS 94.4%, P = 0.57) and regional (95.0% VS 97.2%, P = 0.34) control to ICBT subgroup. The acute and late toxicities rates were comparable between the both subgroups. CONCLUSIONS/SIGNIFICANCE: IMBT boost radiation may be a promising therapeutic selection for deep-seated residual NPC.

Dose-volume parameters and clinical outcome of CT-guided free-hand high-dose-rate interstitial brachytherapy for cervical cancer.

Currently, image-based 3-dimentional (3D) planning brachytherapy allows for a better assessment of gross tumor volume (GTV) and the definition and delineation of target volume in cervix cancer. In this study, we investigated the feasibility of our novel computed tomography (CT)-guided free-hand high-dose-rate interstitial brachytherapy (HDRISBT) technique for cervical cancer by evaluating the dosimetry and preliminary clinical outcome of this approach. Dose-volume histogram (DVH) parameters were analyzed according to the Gynecological GEC-ESTRO Working Group recommendations for image-based 3D treatment in cervical cancer. Twenty cervical cancer patients who underwent CT-guided free-hand HDRISBT between March 2009 and June 2010 were studied. With a median of 5 (range, 4-7) implanted needles for each patient, the median dose of brachytherapy alone delivered to 90% of the target volume (D90) was 45 (range, 33-54) Gyα/ß10 for high-risk clinical target volume (HR-CTV) and 30 (range, 20-36) Gyα/ß10 for intermediate-risk clinical target volume (IR-CTV). The percentage of the CTV covered by the prescribed dose (V100) of HR-CTV with brachytherapy alone was 81.9%-99.2% (median, 96.7%). With an additional dose of external beam radiotherapy (EBRT), the median D90 was 94 (range, 83-104) Gyα/ß10 for HR-CTV and 77 (range, 70-87) Gyα/ß10 for IR-CTV; the median dose delivered to 100% of the target volume (D100) was 75 (range, 66-84) Gyα/ß10 for HR-CTV and 65 (range, 57-73) Gyα/ß10 for IR-CTV. The minimum dose to the most irradiated 2 cc volume (D2cc) was 73-96 (median, 83) Gyα/ß3 for the bladder, 64-98 (median, 73) Gyα/ß3 for the rectum, and 52-69 (median, 61) Gyα/ß3 for the sigmoid colon. After a median follow-up of 15 months (range, 3-24 months), two patients experienced local failure, and 1 showed internal iliac nodal metastasis. Despite the relatively small number of needles used, CT-guided HDRISBT for cervical cancer showed favorable DVH parameters and clinical outcome.

[Application of interstitial brachytherapy via parapharynx involvement transnasal approach to enhance dose in radiotherapy for nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Although intracavitary irradiation (ICI) is usually applied to enhance dose in radiotherapy for early stage nasopharyngeal carcinoma (NPC), its use in parapharyngeal enhancing dose is limited because of dislocation and poor repetition of conventional catheterization. This study was to evaluate the application of a new technique, interstitial brachytherapy via parapharynx involvement transnasal approach, to enhance dose in radiotherapy for NPC. METHODS: Twenty-three naive and recurrent NPC patients with tumor residue of more than 1 cm under nasopharyngeal mucosa or restricted tumor residue in the parapharyngeal space received interstitial brachytherapy between Sep. 2005 and Aug. 2006 via parapharynx involvement transnasal approach under the guidance of sinus endoscopy. The 3-dimensional (3D) planning system was used to delineate target volume, optimize dose distribution, and perform interstitial brachytherapy after CT scan. The depths of catheters under mucosa on the moment of inserting and pulling out were measured. The efficacy and complications were assessed. RESULTS: All catheters were intubated into tumors successfully; the veracity of catheter location was 100%. The submucosa depths of catheters were (9.59+/-2.72) mm when inserted and (9.43+/-2.30) mm when pulled out, without significant difference (t = 0.23,P > 0.05); the shift length was (0.75+/-0.75) mm. The patients were followed up from 3 to 15 months (median, 6 months), and no one dropt out. Three cases of irradiation-associated turbinate adhesion occurred and were cured after lysis; no infection, serious bleeding, palatal perforation, nasopharyngeal necrosis, and other serious complications occurred. All tumors disappeared in 3 months after treatment. No local recurrence and distant metastasis occurred. CONCLUSIONS: The nasopharyngeal and parapharyngeal catheterization with sinus endoscopy guidance is accurate, steady, safe, and feasible. Interstitial brachytherapy is effective for tumor residue in the nasopharynx or parapharyngeal space of NPC patients after radiotherapy without serious complications.