Systems Metabolic Engineering of Saccharomyces cerevisiae for the High-Level Production of (2S)-Eriodictyol.

(2S)-eriodictyol (ERD) is a flavonoid widely found in citrus fruits, vegetables, and important medicinal plants with neuroprotective, cardioprotective, antidiabetic, and anti-obesity effects. However, the microbial synthesis of ERD is limited by complex metabolic pathways and often results in a low production performance. Here, we engineered Saccharomyces cerevisiae by fine-tuning the metabolism of the ERD synthesis pathway. The results showed that the ERD titer was effectively increased, and the intermediate metabolites levels were reduced. First, we successfully reconstructed the de novo synthesis pathway of p-coumaric acid in S. cerevisiae and fine-tuned the metabolic pathway using promoter engineering and terminator engineering for the high-level production of (2S)-naringenin. Subsequently, the synthesis of ERD was achieved by introducing the ThF3'H gene from Tricyrtis hirta. Finally, by multiplying the copy number of the ThF3'H gene, the production of ERD was further increased, reaching 132.08 mg L-1. Our work emphasizes the importance of regulating the metabolic balance to produce natural products in microbial cell factories.

Tumor treating fields for high-grade gliomas.

High-grade gliomas (HGG) are the most common malignant intracranial tumors with poor prognosis. Current treatments have not yielded optimal remission rates; there are no standard treatments for recurrent and drug-resistant gliomas. Tumor treating fields, which was recently approved by the Food and Drug Administration (FDA), could significantly improve progression free survival and the overall survival of glioma patients. In this review, we elaborate on the mechanism of tumor treating fields in tumor cells and detail various preclinical and clinical studies on gliomas. Tumor treating fields could be a promising option for patients with malignant tumors for which there are no standard treatment plans. Moreover, we identify several potential problems for the practical application of tumor treating fields and predict future directions for further studies. Tumor treating fields may be a potential therapy with high efficacy, fewer adverse effects, and high cost-effectiveness.

The Efficacy and Safety of Submandibular Transcatheter Perfusion Anesthesia in Submandibular Gland Surgery.

The present study aims to evaluate the feasibility, safety, and effects of the combined use of submandibular transcatheter perfusion with lingual nerve block and subcutaneous infiltration for anesthetic purposes during submandibular gland surgery. A total of 38 patients with benign tumors, who had undergone resection by submandibular gland surgery were randomly divided into 2 groups. Patients in group A were administered with submandibular anesthesia through catheter perfusion, lingual nerve block, and subcutaneous infiltration anesthesia. Patients in the group B were only treated with lingual nerve block and subcutaneous infiltration anesthesia. The submandibular gland surgery was performed within 5 minutes following anesthesia administration, after which the numerical rating scale (NRS) was evaluated before surgery, during skin incision (T1), during the pulling process of the submandibular gland (T2), during the removal of the submandibular gland (T3), and at 2, 6, 12, and 24 hours post-surgery. The dosage of analgesic drugs was also measured after surgery. The findings revealed no significant difference in NRS before surgery, at T1, 6, 12, and 24 hours after surgery (P > 0.01) while NRS was much lower in group A patients as observed at T2, T3, and 2 hours after surgery when compared with group B (P < 0.01). The combined application of submandibular transcatheter perfusion with lingual nerve block and subcutaneous infiltration can be used as an effective anesthetic method during submandibular gland surgery.

[Pro-angiogenic effects of four Chinese medicines and three herbal prescription in chicken chorioallantoic membrane model].

OBJECTIVE: To observe the pro-angiogenic effect of four Chinese medicines and three herbal prescriptions, screen the effective components from them. METHODS: Chicken chorioallantoic membrane (CAM) model was employed to observe the pro-angiogenic activities of Angelicae Sinensis Radix, Salviae Miltiorrhizae Radix, Notoginseng Radix, Astragali Radix, Xuefuzhuyu decoction, Dangguibuxue decoction and Taohongsiwu decoction, all of them were claimed to promote angiogenesis. The effective components were screened from the extracts. RESULTS: Compared with negative control group, the blood vessel densities in Angelicae Sinensis Radix and Notoginseng Radix groups were not increased significantly (P > 0.05). However, blood vessel densities in Astragali Radix group, Salviae Miltiorrhizae Radix group, Xuefuzhuyu decoction group, Dangguibuxue decoction group and Taohongsiwu decoction group were notably enhanced (P < 0.05). Dangguibuxue decoction showed a more than 90% of increase in blood vessel densities as compared with the negative control group (P < 0.01), and components contained ferulic acid and astragaloside from Dangguibuxue decoction displayed significantly pro-angiogenic effect (P < 0.05). CONCLUSION: Dangguibuxue decoction and its extract, components contained ferulic acid and astragaloside, can improve angiogenesis in CAM model significantly.

[Roller compaction research of Banlangen effervsce tablets].

OBJECTIVE: To study the conditions and parameters of roller compaction of Banlangen effervsce tablet. METHOD: The experimentation adopts L9 (3(4)) orthogonal experiment to study the conditions and parameters of roller compaction of Banlangen effervsce tablet; studied factors that included roller pressure, roller speed and moisture content of power, which influence the result of granule yield and granule friability. RESULT: The optimal technique is: roller pressure at 1.5 MPa; roller speed at 15 Hz; moisture content of power at 1.5%. CONCLUSION: The study of roller compaction technique of Banlangen effervsce tablets provides some technicial consults of its research and production.

[Review of effervescent technique in pharmaceutics research].

Effervescent technique, which can accelerate drug disintegration and dissolution, is usually applied in quick release preparations. Along with the development of pharmaceutical technique and theory, effervescent technique is used more and more extensively to adjust the behavior of drug release, such as in sustained and controlled release preparations, pulsatile drug delivery systems, and so on. This review demonstrated the new applying of effervescent technique in effervescent tablets, stomach floating forms, osmotic pump tablets and pulsatile drug delivery systems, adding to the critical common technique of effervescent forms in drug research. This will be benefit for the further research and development of effervescent technique.

[Effect of yiqijiedu granule on the implanted-tumor protein expression in nasopharyngeal carcinoma].

OBJECTIVE: To investigate the inhibitory mechanism of Yiqijiedu granule on the implanted-tumor growth of nasopharyngeal carcinoma in nude mice. METHODS: Twenty nude mice were injected nasopharyngeal carcinoma cells (HNE1), with 5 x 10(6) cells for a nude mouse. Implanted-tumors grew for 20 d, whose volume reached 1 cm x 1 cm x 1 cm. These nude mice were divided into 2 groups: Yiqijiedu group and control group. The Yiqijiedu group was given Yiqijiedu granule, and the control was given normal saline for 30 d, and then were killed. The volume and weight of implanted-tumors were measured. A 100-mg tissue from implanted-tumors was used to extract total protein by current methods, in which the proteins were separated by two-dimension electrophoresis and stained by silver, and protein profiles of implanted-tumors were obtained. Different proteins in the profiles were analyzed by ImageMaster 2D Elite 4.01. Nineteen different proteins, in which 4 expressed in the Yiqijiedu group, 4 expressed in the control, and the other 11 were differently expressed at 5 folds, were identified by MALDI-TOF-MS. RESULTS: The Yiqijiedu granule could inhibit the growth of implanted-tumors. The volume and weight of implanted-tumors in the Yiqijiedu group were (0.207 +/- 0.023) cm3 and (0.132 +/- 0.021) g respectively, and that of the control was (1.342 +/- 0.298) cm3 and (1.017 +/- 0.015) g ( P < 0.05). The inhibitory rate was 84.58%. The analyses of two-dimension electrophoresis and ImageMaster 2D Elite 4.01 showed that there were 567 +/- 49 protein dots in the Yiqijiedu group and 679 +/- 59 in the control. We found 243 proteins were dys-regulated, of which 112 proteins were observed, up-regulated and the other 131 proteins were down-regulated. MALDI-TOF-MS and Database analysis showed that the high expression proteins were HKR2 protein, 10 Phosphoribosyl pyrophosphate synthetase, TNFR superfamily member, and Apoptosis regulator. The lower expression proteins were Fibulin-3, Zinc finger protein 266, Carboxy terminus of HSP70-interacting protein, et al. CONCLUSION: Yiqijiedu granule could inhibit the growth of nasopharyngeal carcinoma, which may be associated with those proteins regulated by itself.