Eleutheroside B-loaded poly (lactic-co-glycolic acid) nanoparticles protect against renal fibrosis via Smad3-dependent mechanism.

Although renal fibrosis is a common complication of chronic kidney disease (CKD), effective options for its treatment are currently limited. In this study, we evaluated the renal protective effect and possible mechanism of eleutheroside B. In order to solve the allergic reactions, side effects, and low oral bioavailability of eleutheroside B, we successfully prepared PLGA (poly [lactic-co-glycolic acid])-eleutheroside B nanoparticles (NPs) with the diameter of about 128 nm. In vitro and in vivo results showed that eleutheroside B could inhibit expression levels of α-smooth muscle actin (α-SMA) and collagen I. Molecular docking results showed that eleutheroside B bound to Smad3 and significantly decreased the expression of phospho-Smad3 (p-Smad3). Silencing Smad3 reversed the fibrotic protective effect of eleutheroside B in HK2 cells. Furthermore, small animal imaging showed that NPs can selectively accumulate in the UUO kidneys of mice, and retention time reached as long as 7 days. In conclusion, our results suggested that eleutheroside B is a potential drug to protect renal fibrosis and PLGA-eleutheroside B NPs could facilitate specific targeted therapy for renal fibrosis.

Pithohirolide, an antimicrobial tetradepsipeptide from a fungus Pithomyces chartarum.

Pithohirolide (1), a new depsipeptide, was isolated from an ascomycetous fungus Pithomyces chartarum TAMA 581. The planar structure of 1 was elucidated on the basis of NMR and MS analyses and the absolute configuration was determined by the advanced Marfey's analysis, chiral-phase HPLC analysis, and synthesis of degradation product. Compound 1 possesses a cyclic structure comprising (S)-2-hydroxy-3-phenylpropanoic acid, (S)-3-hydroxy-3-phenylpropanoic acid, (S)-2-hydroxyisovaleric acid, and N-methyl-L-alanine, connected via three ester and one amide linkages. Compound 1 exhibited antimicrobial activity against Staphylococcus aureus and Saccharomyces cerevisiae at MIC 3.1 µg ml-1.

Gypenoside XLIX protects against acute kidney injury by suppressing IGFBP7/IGF1R-mediated programmed cell death and inflammation.

BACKGROUND: Acute kidney injury (AKI), characterised by excessive inflammatory cell recruitment and programmed cell death, has a high morbidity and mortality; however, effective and specific therapies for AKI are still lacking. OBJECTIVE: This study aimed to evaluate the renoprotective effects of gypenoside XLIX (Gyp XLIX) in AKI. METHODS: The protective effects of Gyp XLIX were tested in two AKI mouse models established using male C57BL/6 mice (aged 6-8 weeks) by a single intraperitoneal injection of cisplatin (20 mg/kg) or renal ischemia-reperfusion for 40 min. Gyp XLIX was administered intraperitoneally before cisplatin administration or renal ischemia-reperfusion. Renal function, tubular injury, renal inflammation and programmed cell death were evaluated. In addition, the renoprotective effects of Gyp XLIX were also evaluated in cisplatin- or hypoxia-treated tubular epithelial cells. The mechanisms underlying these effects were then explored using RNA sequencing. RESULTS: In vivo, Gyp XLIX substantially suppressed the increase in serum creatinine and blood urea nitrogen levels. Moreover, tubular damage was alleviated by Gyp XLIX as shown by periodic acid-Schiff staining, electron microscopy and molecular analysis of KIM-1. Consistently, we found that Gyp XLIX suppressed renal necroptosis though the RIPK1/RIPK3/MLKL pathway. The anti-inflammatory and antinecroptotic effects were further confirmed in vitro. Mechanistically, RNA sequencing showed that Gyp XLIX markedly suppressed the levels of IGF binding protein 7 (IGFBP7). Co-immunoprecipitation and western blot analysis further showed that Gyp XLIX reduced the binding of IGFBP7 to IGF1 receptor (IGF1R). Additionally, picropodophyllin, an inhibitor of IGF1R, abrogated the therapeutic effects of Gyp XLIX on cisplatin-induced renal cell injury; this finding indicated that Gyp XLIX may function by activating IGF1R-mediated downstream signalling Additionally, we also detected the metabolic distribution of Gyp XLIX after injection; Gyp XLIX had a high concentration in the kidney and exhibited a long retention time. These findings may shed light on the application of Gyp XLIX for AKI treatment clinically. CONCLUSION: Gyp XLIX may serve as a potential therapeutic agent for AKI treatment via IGFBP7/ IGF1R-dependent mechanisms.

Whole-course, individualized, and standardized sequential nutrition therapy for radical resection of tongue cancer: a case report / 华西口腔医学杂志

Surgery, radiotherapy, and chemotherapy are the main treatments for tongue cancer, but the nutritional status of patients is not considered. Nutritional treatment is often not standard or by experience. This article reports a patient with tongue cancer who underwent preoperative chemotherapy and postoperative nutrition treatment. The entire process of individualized and sequential nutrition therapy was adopted, and the nutritional status of the patient was significantly improved. This paper describes the methods of nutrition therapy and evaluation and discusses the treatment process and key points in combination with relevant literature.

Analysis of phytochemical contributors to antioxidant capacity of the peel of Chinese mandarin and orange varieties.

The phytochemicals in the peel of six oranges and ten mandarins including seven wild varieties and three cultivars were systematically characterised using UHPLC-Q-TOF-MS, and the correlation analysis was performed between phytochemicals and antioxidant capacity in order to investigate the phytochemical contributors to antioxidant capacity. The gradient elution was completed within 16 min and 92 compounds were undoubtedly or tentatively identified. Furthermore, the antioxidant capacities were determined using ABTS, DPPH and FRAP methods. The number of compounds, their contents and the antioxidant capacities were sequenced in the same order of the wild mandarins > cultivated mandarins > oranges. The correlation analysis that showed five compounds were significantly correlated with the antioxidant capacity and can act as main contributors to the citrus varieties with high antioxidant capacities. This study is systematic for the metabolites identification of mandarins and oranges and provides valuable information for effective utilisation of citrus peel and their bioactive compounds.

Efficient analysis of phytochemical constituents in the peel of Chinese wild citrus Mangshanju (Citrus reticulata Blanco) by ultra high performance liquid chromatography-quadrupole time-of-flight-mass spectrometry.

An efficient ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method was developed for separation and profiling of phytochemical constituents of Chinese wild mandarin Mangshanju (Citrus reticulata Blanco). All constituents were well separated within 16 min. Based on retention times, accurate mass, MSE fragments, and/or reference standards as well as databases, a total of 81 compounds were unambiguously identified or tentatively assigned including flavonoid glycosides, acylated flavonoid glycosides, flavones, polymethoxylated flavonoids, and limonoids as well as four other compounds. Among them, 22 polymethoxylated flavones and ten polymethoxylated flavanones/chalcones were identified in Mangshanju, more types than other citrus reported before. A basic procedure for identifying flavonoid-O-glycosides and the aglycones including polymethoxylated flavonoids was proposed. In addition, this method was successfully used to analyze another four mandarin germplasms, Cenxi suan ju, Xipi gousi gan, Nanfeng miju, and Or, showing that Mangshanju contained two characteristic compounds distinct from the other four citrus species. This study systematically profiled phytochemical constituents of Mangshanju, which was helpful for further utilization of Mangshanju owing to its abundant bioactive compounds.

[Climate change impacts on yield of Cordyceps sinensis and research on yield prediction model of C. sinensis].

Cordyceps sinensis is a Chinese unique precious herbal material, its genuine producing areas covering Naqu, Changdu in Qinghai Tibet Plateau, Yushu in Qinghai province and other regions. In recent 10 years, C. sinensis resources is decreasing as a result of the blindly and excessively perennial dug. How to rationally protect, develop and utilize of the valuable resources of C. sinensis has been referred to an important field of research on C. sinensis. The ecological environment and climate change trend of Qinghai Tibet plateau happens prior to other regions, which means that the distribution and evolution of C. sinensis are more obvious and intense than those of the other populations. Based on RS (remote sensing)/GIS(geographic information system) technology, this paper utilized the relationship between the snowline elevation, the average temperature, precipitation and sunshine hours in harvest period (April and may) of C. sinensis and the actual production of C. sinensis to establish a weighted geometric mean model. The model's prediction accuracy can reach 82.16% at least in forecasting C. sinensis year yield in Naqu area in every early June. This study can provide basic datum and information for supporting the C. sinensis industry healthful, sustainable development.

Fast Separation and Sensitive Quantitation of Polymethoxylated Flavonoids in the Peels of Citrus Using UPLC-Q-TOF-MS.

A rapid, sensitive, and efficient ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method has been developed to analyze polymethoxylated flavonoids (PMFs) in 14 Citrus peels, including 7 Citrus reticulata (C. reticulata) and 7 Citrus sinensis (C. sinensis). In this study, fast separation can be achieved within 12 min and 42 PMFs have been identified including 33 flavones and 9 flavanones. Most C. reticulata were shown to contain more than 20 PMFs, except Guangxihongpisuanju (GX) containing only 12 PMFs, while most C. sinensis contained fewer than 20 PMFs, except Edangan (EG) containing as many as 32 PMFs. To our knowledge, there are few reports about the quantitation of PMFs using the MS response. Here, a MS quantitative method was established and systematically validated in linearity, precision, and recovery. The linearity was from 1.25 ng/mL to 1.0 µg/mL with the limit of detection (LOD) as low as 75 pg/mL and the limit of quantitation (LOQ) as low as 0.25 ng/mL. Up to 13 PMFs, more types than ever before, were undoubtedly identified and quantitated according to the PMF standards. The results showed that the contents of PMFs in the C. reticulata were generally higher than those in the C. sinensis. This study is systematic for analyzing PMFs and is of great significance because it can provide guidance on utilization of both PMFs and citrus germplasm resources in the future.

Promising Compounds From Murraya exotica for Cancer Metastasis Chemoprevention.

Most of the present anticancer drugs are highly cytotoxic and focus mainly on killing tumor cells rather than slowing the progress of cancer metastasis. Evidence has been reported that bridges the mechanisms of inflammation and tumor invasion. Therefore, we evaluated the potency in cancer metastasis chemoprevention of compounds and a coumarin extracted from Murraya exotica, which is known for its anti-inflammation bioactivity. By carrying out experiments in vitro, we found the root extracts more efficient than the leaf extracts in restraining cell migration of MDA-MB-231 cells, while leaf extracts presented slightly stronger inhibition of tumor cell adhesion at low concentrations. In addition, compared to root extracts, a novel coumarin identified previously from root extracts showed equal inhibition on cancer cell adhesion and less inhibition on cell migration. All extracts used in this study presented low cytotoxicity in vitro. Through comparison of the contents of leaf and root extracts from M exotica, several compounds are considered promising against cancer metastasis. This study evaluates the worth of further development of M exotica to find its effect on cancer metastasis chemoprevention.

Perioperative Transcutaneous Electrical Acupoint Stimulation for Postoperative Pain Relief Following Laparoscopic Surgery: A Randomized Controlled Trial.

OBJECTIVES: This trial was conducted to assess the influence of transcutaneous electrical acupoint stimulation (TEAS) on postoperative pain intensity and the optimal time of TEAS application during perioperative period in patients undergoing laparoscopic surgery. METHODS: From July 2012 to October 2013, 380 patients scheduled for laparoscopic surgery under general anesthesia were randomly assigned to receive sham TEAS (group SSS), preoperative TEAS (group TSS), preoperative TEAS combined with intraoperative TEAS (group TTS) or preoperative TEAS combined with postoperative TEAS (group TST) (n=95 each group). Primary outcomes included resting and activity pain intensity evaluated by visual analog scale at 1, 6, 24, and 48 hours after surgery. RESULTS: At postoperative 6 hours, the activity pain intensity was significantly lower in groups TTS and TST compared with groups SSS and TSS (P<0.001). At postoperative 24 and 48 hours, activity pain intensity decreased in group TST compared with both groups SSS and TSS (P<0.001). The supplemental analgesic requirement was less in group TST compared with group SSS. There was no significant difference in intraoperative anesthetic consumption, postoperative nausea and vomiting and time of the first postoperative flatus or defecation among the 4 groups. The patient satisfactory rate was higher in groups TSS, TTS, and TST compared with group SSS. No side effect related to TEAS was observed during the postoperative 48 hours. DISCUSSION: Combination of preoperative TEAS with intraoperative or postoperative TEAS, rather than preoperative TEAS alone, is an effective and safe adjunctive for management of postoperative pain following laparoscopic surgery.

Mixture of Peanut Skin Extract and Fish Oil Improves Memory in Mice via Modulation of Anti-Oxidative Stress and Regulation of BDNF/ERK/CREB Signaling Pathways.

Long-term use of fish oil (FO) is known to induce oxidative stress and increase the risk of Alzheimer's disease in humans. In the present study, peanut skin extract (PSE), which has strong antioxidant capacity, was mixed with FO to reduce its side effects while maintaining its beneficial properties. Twelve-week Institute of Cancer Research (ICR) mice were used to conduct animal behavior tests in order to evaluate the memory-enhancing ability of the mixture of peanut skin extract and fish oil (MPF). MPF significantly increased alternations in the Y-maze and cognitive index in the novel object recognition test. MPF also improved performance in the water maze test. We further sought to understand the mechanisms underlying these effects. A significant decrease in superoxide dismutase (SOD) activity and an increase in malonyldialdehyde (MDA) in plasma were observed in the FO group. The MPF group showed reduced MDA level and increased SOD activity in the plasma, cortex and hippocampus. Furthermore, the gene expression levels of brain-derived neurotrophic factor (BDNF) and cAMP responsive element-binding protein (CREB) in the hippocampus were increased in the MPF group, while phosphorylation of protein kinase B (AKT), extracellular signal-regulated kinase (ERK) and CREB in the hippocampus were enhanced. MPF improves memory in mice via modulation of anti-oxidative stress and activation of BDNF/ERK/CREB signaling pathways.

1,5-O-Dicaffeoyl-quinic Acid as a Novel Potential NMDA Receptor Inhibitor from Traditional Chinese Medicine Database by Virtual Screening / 中草药·英文版

Objective Neurodegenerative diseases, such as ischemia, traumatic injury, Alzheimer's disease, and Parkinson's disease are characterized by neuronal loss and dysfunction. It is known that glutamate-induced toxicity plays an important role in neurodegenerative diseases. Glutamate toxicity seems to be mediated by excessive influx of Ca2+ into neuronal cells through activation of N-methyl-D-aspartate (NMDA) receptor. To search for potential NMDA receptor inhibitors in traditional Chinese medicine. Methods A series of computer methods including drug-likeness evaluation, ADMET tests as well as molecular docking have been used. Results 1,5-O-dicaffeoyl-quinic acid was identified as NMDA receptor inhibitor by virtual screening. Its neuroprotective activity was further confirmed by in vitro test. 1,5-O-dicaffeoyl-quinic acid showed strong neuroprotection against NMDA-induced cell injury. Conclusion 1,5-O-Dicaffeoylquinic acid may be regarded as a potential NMDA receptor inhibitor for the prevention and treatment of neurodegenerative disorders.