Sulfur (S) fertilizer application in rice (Oryza sativa L.) is crucial in determining rice grain productivity and quality. However, little information is available concerning the effect of S supply ...on cadmium (Cd) uptake and translocation in rice. In this study, both hydroponic and soil experiments were conducted to investigate the influence of S supply on Cd accumulation in rice under two Cd levels (0 and 50 μM), combined with three S concentrations (0, 2.64 and 5.28 mM). The moderate and excessive S supply (2.64 and 5.28 mM) tended to increase plant growth, root length, root and shoot dry weights of rice seedlings, and significantly decreased Cd concentrations in rice plants and grains in the absence or presence of Cd. The subcellular distribution and chemical forms of Cd in roots and shoots also varied with S supply levels. The decreased Cd uptake and translocation in rice grains could be ascribed to the enhanced formation of iron (Fe) plaque on the root surfaces and increased Cd chelation and vacuolar sequestration in roots, since Fe, Mn concentrations in Fe plaque, glutathione and phytochelatins contents, as well as phytochelatin synthase (OsPCS) and tonoplast heavy metal ATPase (OsHMA3) expressions in roots significantly increased with increased S supply. This work provides more insight into the mechanisms of Cd uptake and translocation in rice, and will be helpful for developing strategies to reduce rice grain Cd through S fertilizer application in Cd-contaminated soil.
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•S supply reduces health risk to humans by decreasing Cd accumulation in rice grains.•S supply restrains Cd uptake by enhancing Fe plaque formation on the root surfaces.•S supply reduces Cd translocation by increasing Cd chelation and vacuolar sequestration in roots.
Compound Kushen Injection (CKI) is a Traditional Chinese Medicine (TCM) preparation that has been clinically used in China to treat various types of solid tumours. Although several studies have ...revealed that CKI can inhibit the proliferation of hepatocellular carcinoma (HCC) cell lines, the active compounds, potential targets and pathways involved in these effects have not been systematically investigated. Here, we proposed a novel idea of "main active compound-based network pharmacology" to explore the anti-cancer mechanism of CKI. Our results showed that CKI significantly suppressed the proliferation and migration of SMMC-7721 cells. Four main active compounds of CKI (matrine, oxymatrine, sophoridine and N-methylcytisine) were confirmed by the integration of ultra-performance liquid chromatography/mass spectrometry (UPLC-MS) with cell proliferation assays. The potential targets and pathways involved in the anti-HCC effects of CKI were predicted by a network pharmacology approach, and some of the crucial proteins and pathways were further validated by western blotting and metabolomics approaches. Our results indicated that CKI exerted anti-HCC effects via the key targets MMP2, MYC, CASP3, and REG1A and the key pathways of glycometabolism and amino acid metabolism. These results provide insights into the mechanism of CKI by combining quantitative analysis of components, network pharmacology and experimental validation.
Recurrence and metastasis are the leading causes of tumour-related death in patients with oesophageal squamous cell carcinoma (ESCC). Tumour-infiltrating natural killer cells (NK cells) display ...powerful cytotoxicity to tumour cells and play a pivotal role in tumour therapy. However, the phenotype and functional regulation of NK cells in oesophageal squamous cell carcinoma (ESCC) remains largely unknown.
Single cell suspensions from blood and tissue samples were isolated by physical dissociation and filtering through a 70 μm cell strainer. Flow cytometry was applied to profile the activity and function of NK cells, and an antibody chip experiment was used to identify and quantitate cytokine levels. We studied IL-6 and IL-8 function in primary oesophageal squamous carcinoma and NK cell co-cultures in vitro and by a xenograft tumour model in vivo. Western blotting was used to quantitate STAT3 (signal transducer and activator of transcription 3) and p-STAT3 levels. Finally, we performed an IHC array to analyse IL-6/IL-8 (interleukin 6/interleukin 8) expression in 103 pairs of tumours and matched adjacent tissues of patients with ESCC to elucidate the correlation between IL-6 or IL-8 and clinical characteristics.
The percentages of NK cells in both peripheral blood and tumour tissues from patients with ESCC were significantly increased in comparison with those in the controls and correlated with the clinical characteristics. Furthermore, the decrease in activating receptors and increase in inhibitory receptors on the surface of tumour-infiltrating NK cells was confirmed by flow cytometry. The level of granzyme B, the effector molecule of tumour-infiltrating NK cells, was also decreased. Mechanistically, primary ESCC cells activated the STAT3 signalling pathway on NK cells through IL-6 and IL-8 secretion, leading to the downregulation of activating receptors (NKp30 and NKG2D) on the surface of NK cells. An ex vivo study showed that blockade of STAT3 attenuated the IL-6/IL-8-mediated impairment of NK cell function. Moreover, the expression of IL-6 or IL-8 in tumour tissues was validated by immunohistochemistry to be positively correlated with tumour progression and poor survival, respectively.
Tumour cell-secreted IL-6 and IL-8 impair the activity and function of NK cells via STAT3 signalling and contribute to oesophageal squamous cell carcinoma malignancy.
To evaluate the repeatability and reproducibility of a double-pass instrument (OQASII, Visiomereics SL, Spain), which objectively measures overall optical quality of the human eyes.
The right eye of ...119 healthy subjects with best corrected visual acuity of 20/25 or better was included in this prospective, comparative, observational study. Two separate tests with OQASII were conducted sequentially on the same day by two different examiners. A week later, the first examiner conducted the third measurement. All subjects underwent three consecutive tests during each session. The repeatability and reproducibility of the modulation transfer function cut off frequency (MTF cutoff), the Strehl ratio, the OQAS values (OVs) at contrasts of 100%, 20% and 9%, and the objective scatter index (OSI) were analyzed.
For MTF cutoff, Strehl ratio, OV100%, OV20%, OV9%, and OSI, the mean values were 39.32±9.75cpd, 0.22±0.06, 1.31±0.33, 1.33±0.39, 1.33±0.41, 0.60±0.42, respectively. Repeatability and reproducibility were good with a very low coefficient of variation and high interclass correlation coefficients (>0.88) for all parameters. Bland-Altman plots showed good correlation with 95% limits of agreement ranged from -6.04 to 6.78cpd, -0.05 to 0.05, -0.20 to 0.23, -0.29 to 0.32, -0.40 to 0.42, -0.23 to 0.21 in inter-observer, and -6.56 to 7.42cpd, -0.06 to 0.06, -0.22 to 0.24, -0.30 to 0.32, -0.35 to 0.34, -0.24 to 0.23 in inter-visit, respectively.
The OQASII system yields excellent repeatability and good reproducibility for objective measurements of overall optical quality in clinic.
Hepatocellular carcinoma (HCC) is one of the most extensive and most deadly cancers in the world. Biomarkers for early diagnosis of HCC are still lacking, and noninvasive and effective biomarkers are ...urgently needed. Metabolomics is committed to studying the changes of metabolites under stimulation, and provides a new approach for discovery of potential biomarkers. In the current work,
1
H nuclear magnetic resonance (NMR) metabolomics approach was utilized to explore the potential biomarkers in HCC progression, and the biomarker panel was evaluated by receiver operating characteristic (ROC) curve analyses. Our results revealed that a biomarker panel consisting of hippurate, creatinine, putrescine, choline, and taurine might be involved in HCC progression. Functional pathway analysis showed that taurine and hypotaurine metabolism is markedly involved in the occurrence and development of HCC. Furthermore, our results indicated that the TPA activity and the level and expression of PKM2 were gradually increased in HCC progression. This research provides a scientific basis for screening potential biomarkers of HCC.
Graphical abstract
Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on ...nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more "holistic view" approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a 1H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help our further understanding of the effect of GA in hepatosteatosis mice.
Background： Menopausal symptoms and sleep difficulty were physiological processes that were affected by genetic and other factors. This study was to investigate the prevalence of menopausal symptoms ...and sleep quality in menopausal transition （MT） and postmenopause （PM） women in Taiyuan, Shanxi. Methods： A community-based survey of women＇s menopausal symptoms and sleep quality was conducted between July 2012 and May 2013 at six municipal districts of Taiyuan, Shanxi. A sample of 2429 women aged 40-59 years was divided into four groups： early MT, late MT, early PM, and late PM. Sleep quality in the past 2 weeks before the interview was recorded. The data were analyzed using SPSS 16.0. Results： The prevalence of menopausal symptoms was 49.8%. Mild, moderate, and severe symptoms were observed in 28.9%, 18.5%, and 2.5% of participants, respectively. The highest prevalence of menopausal symptoms occurred in the early postmenopausal stage; the subsequences were the late postmenopausal stage and the early MT stage. Interestingly, among the 13 items of modified Kupperman index, the five most common symptoms were fatigue, arthralgia and myalgia, decreased libido, insomnia, and nervousness. Meanwhile, 55% perimenopausal women had poor sleep. Conclusions： Menopausal symptoms are common but mild among women in Taiyuan, Shanxi during MT and PM. In these stages, the prevalence of poor sleep is high.
(AR) or its extract has been used as an herbal medicine and dietary supplement in China, Europe, and the United States. The gut microbiota could provide new insights for exploring dietary ...supplements' underlying mechanism on organisms. However, no reports have focused on the regulatory effect of AR on the gut microbiota as a dietary supplement. In this study, healthy ICR mice of either sex were divided into AR and control (CON) groups and given AR water extract (4.55 mg/kg·day
) or saline by gavage for 14 days, respectively. Then 16S rRNA gene sequencing and ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry-based fecal metabolomics were integrated to investigate the benefits of dietary AR. Weighted gene coexpression network analysis was also introduced to investigate the metabolites with highly synergistic changes. AR supplementation influenced the structure of intestinal microflora, especially enriching short-chain fatty acid-producing bacteria
,
, and
. AR also significantly altered the fecal metabolome, mainly related to amino acid metabolism, nucleotide metabolism, and bile acid (BA) metabolism. Moreover, the increased secondary BAs and BA-sulfates might closely relate to intestinal microflora. These findings provide valuable insights for future research of dietary AR as a functional food.
Polygala tenuifolia Willd. is a traditional Chinese herbal medicine that is widely used in treating nervous system disorders. Triterpene saponins in P. tenuifolia (polygala saponins) have excellent ...biological activity. As a precursor for the synthesis of presenegin, oleanolic acid (OA) plays an important role in the biosynthesis of polygala saponins. However, the mechanism behind the biosynthesis of polygala saponins remains to be elucidated. In this study, we found that CYP716A249 (GenBank: ASB17946) oxidized the C-28 position of β-amyrin to produce OA. Using quantitative real-time PCR, we observed that CYP716A249 had the highest expression in the roots of 2-year-old P. tenuifolia, which provided a basis for the selection of samples for gene cloning. To identify the function of CYP716A249, the strain R-BE-20 was constructed by expressing β-amyrin synthase in yeast. Then, CYP716A249 was co-expressed with β-amyrin synthase to construct the strain R-BPE-20 by using the lithium acetate method. Finally, we detected β-amyrin and OA by ultra-HPLC-Q Exactive hybrid quadrupole-Orbitrap high-resolution accurate mass spectrometry and GC-MS. The results of this study provide insights into the biosynthesis pathway of polygala saponins.
Parkinson's disease (PD) is a common neurodegenerative disease, and the pathogenesis of PD is closely related to mitochondrial dysfunction. Previous studies have indicated that traditional Chinese ...medicine composition of Huangqin Decoction (HQD), including
Scutellariae Radix, licorice
, and
Paeoniae Radix Alba
, has therapeutic effects on PD, but whether HQD has a therapeutic effect on PD has not been reported. In this study, the protective effects of HQD on rotenone-induced PD rats were evaluated by behavioral assays (open field, rotating rod, suspension, gait, inclined plate, and grid) and immunohistochemistry. The mechanisms of HQD on attenuation of mitochondrial dysfunction were detected by biochemical assays and mitochondrial metabolomics. The results showed that HQD (20 g/kg) can protect rats with PD by improving motor coordination and muscle strength, increasing the number of tyrosine hydroxylase (TH)-positive neurons in rats with PD. Besides, HQD can improve mitochondrial dysfunction by increasing the content of adenosine triphosphate (ATP) and mitochondrial complex I. Mitochondrial metabolomics analysis revealed that the ketone body of acetoacetic acid (AcAc) in the rotenone group was significantly higher than that of the control group. Ketone bodies have been known to be used as an alternative energy source to provide energy to the brain when glucose was deficient. Further studies demonstrated that HQD could increase the expression of glucose transporter GLUT1, the content of tricarboxylic acid cycle rate-limiting enzyme citrate synthase (CS), and the level of hexokinase (HK) in rats with PD but could decrease the content of ketone bodies AcAc and β-hydroxybutyric acid (β-HB) and the expression of their transporters (MCT1). Our study revealed that the decrease of glucose metabolism in the rotenone group was parallel to the increase of substitute substrates (ketone bodies) and related transporters, and HQD could improve PD symptoms by activating the aerobic glycolysis pathway.
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