Potential Therapeutic Mechanism of Traditional Chinese Medicine on Diabetes in Rodents: A Review from an NMR-Based Metabolomics Perspective.

Traditional Chinese medicine (TCM) has been used to treat diabetes for a long time, but its application has not been widely accepted due to unstandardized product quality and complex pharmacological mechanisms. The modernization of TCM is crucial for its further development, and in recent years the metabolomics technique has largely driven its modernization. This review focuses on the application of NMR-based metabolomics in diabetic therapy using TCM. We identified a series of metabolic pathways that altered significantly after TCM treatment, providing a better understanding of the metabolic mechanisms of TCM for diabetes care.

[High quality standard of Scutellariae Radix based on plant metabolomics and index components].

Scutellariae Radix(SR), derived from the dried root of Scutellaria baicalensis in the family Lamiaceae, commonly serves as Chinese medicinal material. Affected by producing areas, growing years, and harvesting periods, the quality of SR fluctuates in the market. However, baicalin≥9% in SR required in the Chinese Pharmacopoeia(2020 edition) can only determine the qualified SR but cannot identify high-quality SR. To improve the quality control methods of SR, the present study analyzed the accumulation of metabolites in SR of different growth years by plant metabolomics, and identified 28 metabolites increasing with growth years(1-3 years). Subsequently, 14 main metabolites were quantitatively analyzed by ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry(UPLC-QQQ-MS). Among them, baicalin, wogonoside, baicalein, and wogonin with high content and good activity were selected as the index components of SR for quality evaluation. A high-performance liquid chromatography(HPLC) method was established to determine the content of four index components in 32 batches of SR from different producing areas, harvesting perio-ds, and growth years. The results showed that the growth years could greatly affect the content of index components. The total content of four index components in 2-year SR was the highest, followed by the 3-/4-year SR and 1-year SR. Based on HPLC data and verification results by enterprises, baicalin ≥12.0%, wogonoside ≥2.3%, baicalein ≥0.1%, and wogonin ≥0.03% were proposed as the evaluation criteria for the high-quality SR. The findings of this study are expected to provide a basis for improving the quality of SR.

Auricular Acupressure for Insomnia in Patients With Maintenance Hemodialysis: A Systematic Review and Meta-Analysis.

Background: Insomnia is one of the common problems in patients with maintenance hemodialysis (MHD). Previous studies have reported the beneficial effects of auricular acupressure (AA) for insomnia in patients with MHD. This study aimed to critically evaluate the efficacy and safety of AA for insomnia in patients with MHD. Methods: Web of Science, Embase, PubMed, Cochrane Library, Chinese Biomedical Database, Wanfang Data, Chinese Science and Technology Periodicals database, and China National Knowledge Infrastructure were systematically searched from inception to April 30, 2020, to identify any eligible randomized controlled trials. MHD patients with insomnia were included regardless of age, gender, nationality, or race. The experimental interventions included AA alone or AA combined with other therapies. The control interventions included placebo, no treatment, or other therapies. The primary outcome was sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI). RevMan 5.3 software was used for statistical analysis. Results: Eight studies involving 618 participants were included for statistical analysis. A meta-analysis showed no significant difference of PSQI global score after 8 weeks of AA treatment compared with estazolam (p = 0.70). Other narrative analyses revealed that PSQI global score was significantly attenuated after AA treatment in comparison with mental health education (p = 0.03, duration of 4 weeks; p = 0.02, duration of 8 weeks), AA plus routine nursing care compared with routine nursing care alone (p < 0.0001), and AA plus footbath compared with footbath alone (p = 0.01), respectively. A meta-analysis showed that AA could significantly increase the response rate (reduction of PSQI global score by 25% and more) in comparison with estazolam (p = 0.01). Other narrative analyses reported that the response rate was significantly increased after AA treatment compared with sham AA (p = 0.02), AA compared with mental health education (p = 0.04), and AA plus routine nursing care compared with routine nursing care alone (p = 0.0003), respectively. Conclusion: The present findings suggest that AA may be an alternative treatment for insomnia in patients with MHD. However, more large-scale, high-quality trials are still warranted to confirm these outcomes.

Activation of an AKT/FOXM1/STMN1 pathway drives resistance to tyrosine kinase inhibitors in lung cancer.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have demonstrated clinical benefits in the treatment of several tumour types. However, the emergence of TKI resistance restricts the therapeutic effect. This study uses non-small cell lung cancer (NSCLC) to explore the mechanisms contributing to TKI resistance in tumours. METHODS: Biological phenotypes and RNA microarray expression data were analysed in NSCLC cells with and without TKI pretreatment. Specific inhibitors and siRNAs were used to validate the direct involvement of an AKT/FOXM1/STMN1 pathway in TKI resistance. Patients' tissues were analysed to explore the clinical importance of FOXM1 and STMN1. RESULTS: In vitro and in vivo studies showed that TKIs induced the enrichment of cancer stem cells (CSC), promoted epithelial to mesenchymal transition (EMT), and conferred multidrug resistance on NSCLC cells in a cell type- and TKI class-dependent manner. Mechanistically, TKIs activated an AKT/FOXM1/STMN1 pathway. The crucial role of this pathway in TKI-induced enrichment of CSC and drug resistance was verified by silencing FOXM1 and STMN1 or blocking the AKT pathway. Additionally, overexpression of STMN1 was associated with upregulation of FOXM1 in advanced NSCLC patients, and STMN1/FOXM1 upregulation predicted a poor outcome. CONCLUSIONS: Our findings elucidate an additional common mechanism for TKI resistance and provide a promising therapeutic target for reversing TKI resistance in NSCLC.

A 11 mW 2.4 GHz 0.18 µm CMOS Transceivers for Wireless Sensor Networks.

In this paper, a low power transceiver for wireless sensor networks (WSN) is proposed. The system is designed with fully functional blocks including a receiver, a fractional-N frequency synthesizer, and a class-E transmitter, and it is optimized with a good balance among output power, sensitivity, power consumption, and silicon area. A transmitter and receiver (TX-RX) shared input-output matching network is used so that only one off-chip inductor is needed in the system. The power and area efficiency-oriented, fully-integrated frequency synthesizer is able to provide programmable output frequencies in the 2.4 GHz range while occupying a small silicon area. Implemented in a standard 0.18 µm RF Complementary Metal Oxide Semiconductor (CMOS) technology, the whole transceiver occupies a chip area of 0.5 mm² (1.2 mm² including bonding pads for a QFN package). Measurement results suggest that the design is able to work at amplitude shift keying (ASK)/on-off-keying (OOK) and FSK modes with up to 500 kbps data rate. With an input sensitivity of -60 dBm and an output power of 3 dBm, the receiver, transmitter and frequency synthesizer consumes 2.3 mW, 4.8 mW, and 3.9 mW from a 1.8 V supply voltage, respectively.

Fish Oil Supplements Lower Serum Lipids and Glucose in Correlation with a Reduction in Plasma Fibroblast Growth Factor 21 and Prostaglandin E2 in Nonalcoholic Fatty Liver Disease Associated with Hyperlipidemia: A Randomized Clinical Trial.

UNLABELLED: Fish oil has been used effectively in the treatment of cardiovascular disease via triglyceride reduction and inflammation modulation. This study aimed to assess the effects of fish oil on patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia. Eighty participants with NAFLD associated with hyperlipidemia were randomly assigned to consume fish oil (n=40, 4 g/d) or corn oil capsules (n=40, 4 g/d) for 3 months in a double-blind, randomized clinical trial. Blood levels of lipids, glucose and insulin, liver enzymes, kidney parameters and cytokines at baseline and the end of the study were measured. Seventy people finished the trial. Plasma concentrations of eicosapentaenoic acid and docosahexaenoic acid significantly increased in the fish oil group after intervention. After adjustment for age, gender and BMI, fish oil significantly decreased fasting serum concentrations of total cholesterol, triglyceride, apolipoprotein B and glucose (by (mean±SD) 0.49±0.43 mmol/L, 0.58±0.89 mmol/L, 0.28±0.33 g/L and 0.76±0.56 mmol/L, respectively, P<0.05), as well as alanine aminotransferase and γ-glutamyl transpeptidase levels (by (median (interquartile)) 9.0(0.5, 21.5) and 7.0(2.2, 20.0) IU/L, respectively, P<0.05), significantly increased serum adiponectin levels (by 1.29±0.62 µg/mL, P<0.001), and reduced serum levels of tumor necrosis factor α, leukotrienes B4, fibroblast growth factor 21 (FGF21), cytokeratin 18 fragment M30 and prostaglandin E2 (by 1.70±1.18 pg/mL, 0.59±0.28 ng/mL, 121±31 pg/mL, 83±60 IU/L and 10.9±2.3 pg/mL, respectively, P<0.001). Corn oil had no effect except for increasing serum creatinine concentrations by 7.7±8.9 µmol/L (P=0.008). The effects of fish oil on lipids, glucose and γ-glutamyl transpeptidase were positively correlated with the reductions of serum FGF21 and prostaglandin E2 concentrations after adjustment for age, gender and BMI (r = 0.275 to 0.360 and 0.261 to 0.375, respectively, P<0.05). In conclusion, our findings suggest that fish oil can benefit metabolic abnormalities associated with NAFLD treatment. TRIAL REGISTRATION: ChiCTR-TRC-12002380.

Estrogen receptor and PI3K/Akt signaling pathway involvement in S-(-)equol-induced activation of Nrf2/ARE in endothelial cells.

S-(-)equol, a natural product of the isoflavone daidzein, has been reported to offer cytoprotective effects with respect to the cardiovascular system, but how this occurs is unclear. Interestingly, S-(-)equol is produced by the human gut, suggesting a role in physiological processes. We report that treatment of human umbilical vein endothelial cells and EA.hy926 cells with S-(-)equol induces ARE-luciferase reporter gene activity that is dose and time dependent. S-(-)equol (10-250 nM) increases nuclear factor-erythroid 2-related factor 2 (Nrf2) as well as gene products of Nrf2 target genes heme oxygenase-1 (HO-1) and NAD(P)H (nicotinamide-adenine-dinucleotide-phosphate) quinone oxidoreductase 1 (NQO1). Endothelial cells transfected with an HA-Nrf2 expression plasmid had elevated HA-Nrf2, HO-1, and NQO1 in response to S-(-)equol exposure. S-(-)equol treatment affected Nrf2 mRNA only slightly but significantly increased HO-1 and NQO1 mRNA. The pretreatment of cells with specific ER inhibitors or PI3K/Akt (ICI182,780 and LY294002) increased Nrf2, HO-1, and NQO1 protein, impaired nuclear translocation of HA-Nrf2, and decreased ARE-luciferase activity. Identical experiments were conducted with daidzein, which had effects similar to S-(-)equol. In addition, DPN treatment (an ERß agonist) induced the ARE-luciferase reporter gene, promoting Nrf2 nuclear translocation. Cell pretreatment with an ERß antagonist (PHTPP) impaired S-(-)equol-induced Nrf2 activation. Pre-incubation of cells followed by co-treatment with S-(-)equol significantly improved cell survival in response to H2O2 or tBHP and reduced apoptotic and TUNEL-positively-stained cells. Notably, the ability of S-(-)equol to protect against H2O2-induced cell apoptosis was attenuated in cells transfected with an siRNA against Nrf2. Thus, beneficial effects of S-(-)equol with respect to cytoprotective antioxidant gene activation may represent a novel strategy to prevent and treat cardiovascular diseases.