Biotransformation of Flavonoids Improves Antimicrobial and Anti-Breast Cancer Activities In Vitro.

Coarse cereals are rich in flavonoids, which are bioactive substances with a wide range of functions. Biotransformation is considered an emerging approach to methylate flavonoids, displaying prominent regio- and stereoselectivity. In the current study, liquiritigenin, naringenin, and hesperidin flavonoids were biotransformed using O-methyltransferases that were heterologously expressed in Saccharomyces cerevisiae BJ5464-NpgA. Nuclear magnetic resonance (NMR) spectroscopy was used together with high-resolution mass spectroscopy analysis to determine the structures of the resulting methylated transformants, and their antimicrobial and antiproliferation activities were also characterized. Among the five methylated flavonoids obtained, 7-methoxy-liquiritigenin had the strongest inhibitory effect on Candida albicans SC5314 (C. albicans SC5314), Staphylococcus aureus ATCC6538 (S. aureus ATCC6538), and Escherichia coli ATCC25922 (E. coli ATCC25922), which increased 7.65-, 1.49-, and 0.54-fold in comparison to the values of their unmethylated counterparts at 200, 250, and 400 µM, respectively. The results suggest that 3'-methoxyhesperetin showed the best antiproliferative activity against MCF-7 cells with IC50 values of 10.45 ± 0.45 µM, which was an increase of more than 14.35-fold compared to that of hesperetin. These results indicate that methylation enhances the antimicrobial activities and antiproliferative effects of flavonoids. The current study provides an experimental basis for further research on flavonoids as well as flavonoid-containing crops in the development of antimicrobial and anti-breast cancer drugs in addition to supplementary and health foods. The biotransformation method is ideal, as it represents a means for the sustainable production of bioactive flavonoids.

Experimental Study on Glaze Icing Detection of 110 kV Composite Insulators Using Fiber Bragg Gratings.

Icing detection of composite insulators is essential for the security and stability of power grids. As conventional methods have met difficulties in harsh weather, a 110 kV composite insulator with embedded Fiber Bragg Gratings (FBGs) was proposed for detecting glaze icing in this paper. FBG temperature compensation sensors in ceramic tubes were adopted for simultaneous measurement of icicle loads and temperature. Then, temperature calibration experiments and simulated icicle load experiments were carried out to obtain temperature and icicle load characteristics of FBGs. The results showed that temperature sensitivities of FBG strain sensors and FBG temperature compensation sensors were 18.16 pm/°C, and 13.18 pm/°C, respectively. Besides, wavelength shifts were linearly related to icicle loads within the polar angle range of -60° to 60°, and the load coefficient of FBG facing the icicle was -34.6 pm/N. In addition, the wavelength shift generated by several icicles was equal to the sum of wavelength shifts generated by each icicle within the polar angle range of -15° to 15°. Finally, icicles can cause wavelength shifts of FBGs within a big shed spacing. The paper provides a novel icing detection technology for composite insulators in transmission lines.

A Preliminary Study on the Establishment of the PDTX Model.

OBJECTIVE: The current study aims to explore the establishment of the patient-derived tumor xenograft (PDTX) model. MATERIALS AND METHODS: Twenty patients with gastric cancer, 10 males and 10 females, were enrolled in the current study. Firstly, the volume, invasion and metastasis of the xenografts were observed. Subsequently, the correlation between tumor tissues of the PDTX mouse model and the patients' primary tumor tissues was evaluated by pathological H&E staining and immunohistochemistry. RESULTS: The results showed that the PDTX models corresponding to 15 of the 20 patients were successfully established, and the success rate of PDTX model establishment was 75%. Furthermore, the PDTX models maintained the differentiation degree, morphological characteristics and structural characteristics of tumor cells. CONCLUSION: A PDTX model can be used as a substitute for cancer patients in clinical practice and may be suitable for clinical pharmacodynamic screening and new drug development.

Establishment of the PDTX model of gynecological tumors.

OBJECTIVE: Fresh tumor tissues from patients with gynecological tumors were obtained by surgery or biopsy, and transplanted into NOD-Prkdcem26ll2rgem26Nju (NCG) mice to establish a patient-derived tumor xenograft (PDTX). MATERIALS AND METHODS: A total of 15 patients with gynecologic tumors were enrolled into the present study. Among these patients, 12 patients had epithelial fallopian tube/ovarian/peritoneal cancer, one patient had metastatic ovarian cancer, and two patients had cervical cancer. Furthermore, among these patients, three patients were treated with puncture or microscopy biopsy, six patients underwent laparoscopic surgery, and six patients underwent robotic surgery. The tumor formation latency, tumor formation rate, tumor volume, tumor invasion and metastasis of the transplanted tumor were observed, the consistency of the PDTX model tumor tissue and patient's primary tumor tissue was compared by pathological H&E staining, and pharmacodynamics testing was performed. RESULTS: Seven of 15 PDTX models were successfully established, with a success rate of 46.7%. The tumor formation time ranged within 21-130 days, with a median tumor formation time of 73 days. The PDTX model maintained the differentiation, morphological and structural characteristics of tumor cells, and the pharmacodynamic test was completed in five patients. CONCLUSION: The PDTX model is highly consistent with the pathology of the patient's tumor, and can be used as a substitute for clinical patients to guide the accurate treatment and scientific research of gynecological tumors.

Detection of Glaze Icing Load and Temperature of Composite Insulators Using Fiber Bragg Grating.

Conventional methods for the online monitoring of icing conditions of composite insulators suffer from difficulties. To solve this issue, a novel method is first proposed to detect glaze icing load via embedding three optical fibers with fiber Bragg gratings (FBGs) into a 10 kV composite insulator. Specifically, FBG temperature compensation sensors were packaged in ceramic tubes to solve strain and temperature cross-sensitivity. Temperature effect experiments and simulated glaze icing load experiments were performed to verify the feasibility of the proposed method. The results show that temperature sensitivities of all FBGs are identical (i.e., 10.68 pm/°C), which achieves a simultaneous measurement of temperature and strain. In addition, the proposed method can detect glaze icing load of the composite insulator above 0.5 N (i.e., 15% of icicle bridged degree) in the laboratory.

NLP based congestive heart failure case finding: A prospective analysis on statewide electronic medical records.

BACKGROUND: In order to proactively manage congestive heart failure (CHF) patients, an effective CHF case finding algorithm is required to process both structured and unstructured electronic medical records (EMR) to allow complementary and cost-efficient identification of CHF patients. METHODS AND RESULTS: We set to identify CHF cases from both EMR codified and natural language processing (NLP) found cases. Using narrative clinical notes from all Maine Health Information Exchange (HIE) patients, the NLP case finding algorithm was retrospectively (July 1, 2012-June 30, 2013) developed with a random subset of HIE associated facilities, and blind-tested with the remaining facilities. The NLP based method was integrated into a live HIE population exploration system and validated prospectively (July 1, 2013-June 30, 2014). Total of 18,295 codified CHF patients were included in Maine HIE. Among the 253,803 subjects without CHF codings, our case finding algorithm prospectively identified 2411 uncodified CHF cases. The positive predictive value (PPV) is 0.914, and 70.1% of these 2411 cases were found to be with CHF histories in the clinical notes. CONCLUSIONS: A CHF case finding algorithm was developed, tested and prospectively validated. The successful integration of the CHF case findings algorithm into the Maine HIE live system is expected to improve the Maine CHF care.

[Effects of Chinese herbal medicine Liuwei Dihuang Pill and its main monomer catalpol on transforming growth factor-ß1/Smad pathway in HK-2 cells].

OBJECTIVE: To observe the effects of sera containing Liuwei Dihuang Pill (LDP), a compound traditional Chinese herbal medicine, and its monomer catalpol on transforming growth factor-ß1 (TGF-ß1)/Smad pathway in HK-2 cells. METHODS: Wistar rats were intragastrically administered with LDP twice daily for 3 days and then sera were obtained. HK-2 cells were cultured at different concentrations of serum containing LDP. Lactate dehydrogenase (LDH) activity in the medium and cell activity, tested by methyl thiazolyl tetrazolium (MTT) method, were combined to determine the best concentration of the pill. Hepatocyte growth factor (HGF) was used as a positive control, while Western blotting was applied to observe the effects of sera containing LDP and catalpol on Smad2 phosphorylation and protein expressions of Smad2, Smad7 and SnoN. RESULTS: The 10% concentration of serum containing LDP was selected to carry out this study, as it showed no change of LDH activity in the medium and vitality of cells cultured with serum from normal rats. Similar to the mechanisms of HGF, the 10% concentration of serum containing LDP significantly inhibited the phosphorylation of Smad2 protein and up-regulated the expression of the Smad transcriptional co-repressor SnoN in TGF-ß1-stimulated HK-2 cells. Catalpol inhibited phosphorylation of Smad2 without affecting SnoN protein expression. Neither serum containing LDP nor catalpol showed typical regulation effects on Smad7 expression in TGF-ß1-stimulated HK-2 cells. CONCLUSION: Serum containing LDP at 10% concentration has a potent antagonistic action on TGF-ß1/Smad pathway in TGF-ß1-stimulated HK-2 cells, which is similar to HGF. Catalpol is one of the most important monomers and plays a key role in LDP.

[Effect of Liuwei Dihuang pill on expression of NF-kappaB in kidney lesion induced by gentamicin in rats].

OBJECTIVE: To study the effect of Liuwei Dihuang Pill on kidney lesion in rats induced by gentamicin and its mechanism. METHODS: Rats were divided into three groups: control group, gentamicin group, Liuwei Dihuang Pill group randomly. Parameters of kidney function and oxidative production in three groups were tested by biochemical analysis. Nuclear Factor-kappaB (NF-kappaB) protein were determined by western blotting. RESULTS: Parameters of weight, kidney indexes, oxidative production MDA and enzyme activity of NOS in kidney cortex of gentamicin group significantly increased (P < 0.05), and enzyme activity of SOD significantly decreased (P < 0. 05). The protein expression of NF-kappaB in gentamicin group was significantly up-regulated. After treatment with Liuwei Dihuang Pill, the above-mentioned up-regulated parameters were all significantly inhibited. CONCLUSION: Liuwei Dihuang Pill can inhibit the expression of NF-kappaB protein, so as to alleviate the renal oxidative lesion, and it may be one of the important mechanisms for treating gentamicin induced kidney lesion.