ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Ixeris sonchifolia alias Kudiezi, it was named Ixeris sonchifolia (Bunge) Hance, a synonym for Crepidiastrum sonchifolium (Bunge) Pak & Kawano in the https://www.iplant.cn/. And it was first published in J. Linn. Soc., Bot. 13: 108 (1873), which was named Ixeris sonchifolia (Maxim.) Hance in the MPNS (http://mpns.kew.org). As a widely distributed medicinal and edible wild plant, it possesses unique bitter-cold characteristics and constituents with various pharmacological activities. Its main antitumor substances, same as artemisinin and paclitaxel, are classified as terpenoids and have become research foci in recent years. However, its specific biological activity and role in antitumor treatment remain largely unclear. AIM OF THE STUDY: This study aimed to elucidate the molecular targets and potential mechanisms of hepatocellular carcinoma apoptosis induced by Ixeris sonchifolia. MATERIALS AND METHODS: We used network pharmacology methods to analyze and screen the active ingredients and possible underlying mechanisms of Ixeris sonchifolia in treating liver cancer and employed integrative time- and dose-dependent toxicity, transcriptomics, and molecular biology approaches to comprehensively verify the function of Ixeris sonchifolia extract (IsE) in human hepatoblastoma cell (HepG2) apoptosis and its potential mechanism. RESULTS: A total of 169 common targets were screened by network pharmacology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that IsE inhibited HepG2 cell activity in a time- and dose-dependent manner. Western blot analysis confirmed that IsE promoted HepG2 cell apoptosis by inhibiting the PI3K/AKT signaling pathway and that the PI3K/AKT inhibitor LY294002 also substantially enhanced IsE-induced apoptosis. The PI3K/AKT signaling pathway exhibited significant differences compared to that in the control group. CONCLUSION: Combining network pharmacology with experimental verification, IsE inhibited mitochondrial function and the PI3K/AKT pathway while inducing hepatoma cell apoptosis. IsE may have promising potential for liver cancer treatment and chemoprevention.
Subject(s)
Asteraceae , Carcinoma, Hepatocellular , Drugs, Chinese Herbal , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Network Pharmacology , Apoptosis , Molecular Docking SimulationABSTRACT
BACKGROUND: Mikania micrantha is a vine with strong invasion ability, and its strong sexual reproduction ability is not only the main factor of harm, but also a serious obstacle to control. M. micrantha spreads mainly through seed production. Therefore, inhibiting the flowering and seed production of M. micrantha is an effective strategy to prevent from continuing to spread. RESULT: The flowering number of M. micrantha is different at different altitudes. A total of 67.01 Gb of clean data were obtained from nine cDNA libraries, and more than 83.47% of the clean reads were mapped to the reference genome. In total, 5878 and 7686 significantly differentially expressed genes (DEGs) were found in E2 vs. E9 and E13 vs. E9, respectively. Based on the background annotation and gene expression, some candidate genes related to the flowering pathway were initially screened, and their expression levels in the three different altitudes in flower bud differentiation showed the same trend. That is, at an altitude of 1300 m, the flower integration gene and flower meristem gene were downregulated (such as SOC1 and AP1), and the flowering inhibition gene was upregulated (such as FRI and SVP). Additionally, the results showed that there were many DEGs involved in the hormone signal transduction pathway in the flower bud differentiation of M. micrantha at different altitudes. CONCLUSIONS: Our results provide abundant sequence resources for clarifying the underlying mechanisms of flower bud differentiation and mining the key factors inhibiting the flowering and seed production of M. micrantha to provide technical support for the discovery of an efficient control method.
Subject(s)
Mikania , Mikania/genetics , Altitude , Gene Expression Profiling , Flowers/genetics , Reproduction , Transcriptome , Gene Expression Regulation, PlantABSTRACT
OBJECTIVE: To identify the biological function and metabolic pathway of differential metabolites in follicular fluid of senile patients with kidney qi deficiency undergoing in vitro fertilization-embryo transfer (IVF-ET) and observe the effect of kidney-invigorating herbs on IVF outcomes in senile patients. METHODS: A total of 95 women undergoing IVF treatment were recruited and divided into three groups, including 34 cases in the treatment group (the senile patients with kidney qi deficiency after the intervention of Chinese medicine), 31 cases in the experiment group (the senile patients with kidney qi deficiency of no intervention of Chinese medicine), and 30 cases in the control group (young women with infertility due to male factor). The three groups of women were treated with long protocol ovarian hyperstimulation; the treatment group was given Qi-Zi-Yu-Si decoction on the day of HCG downregulation. Their IVF clinical outcomes were observed. The metabolites changes of kidney qi deficiency syndrome were analyzed in follicular fluid metabolomics using liquid chromatography-mass spectrometry (UPLC-MS/MS). RESULTS: The syndrome score of kidney qi deficiency syndrome in the treatment group was significantly improved after treatment (P < 0.01). Compared with the experiment group, the available embryo rate and implantation rate were increased, and the difference was statistically significant (P < 0.05). Progesterone, indoleacrylic acid, 2-propenyl 1-(1-propenylsulfinyl) propyl disulfide, N-acetyltryptophan, decanoylcarnitine, 20a-dihydroprogesterone, testosterone acetate, eicosatrienoic acid, 1H-indole-3-carboxaldehyde, choline, phosphorylcholine, and tryptophan were downregulated in the treatment group. Through pathway analysis, glycerophospholipid metabolism and steroid hormone biosynthesis were regulated in senile patients with kidney qi deficiency after Qi-Zi-Yu-Si decoction intervention. CONCLUSION: Qi-Zi-Yu-Si decoction can effectively improve the IVF outcome and clinical symptoms of senile patients. Follicular fluid metabolites were significantly changed in senile infertile women with kidney qi deficiency, and the mechanism by which kidney-invigorating herbs improve IVF treatment outcomes may be related to glycerophospholipid metabolism and steroid hormone biosynthesis. This study was registered in the Chinese Clinical Trials Registry Platform (ChiCTR1800014422).
ABSTRACT
Effective and complete control of the invasive weed Mikania micrantha is required to avoid increasing damages. We exogenously applied indole 3-acetic acid (IAA), gibberellin (GA), and N-(2-Chloro-4-pyridyl)-N'-phenylurea (CPPU), and their combinations i.e. IAA + CPPU (IC), GA + CPPU (GC), and GA + IAA + CPPU (GIC), at 5, 10, 25, 50, and 75 ppm against distilled water as a control (CK), to examine their effects on the weed. The increasing concentrations of these hormones when applied alone or in combination were fatal to M. micrantha and led towards the death of inflorescences and/or florets. CPPU and GIC were found as the most effective phytohormones. Transcriptome analysis revealed differential regulation of genes in auxin, cytokinin, gibberellin and abscisic acid signaling pathways, suggesting their role in the prohibition of axillary bud differentiation. Collectively, CPPU and GIC at a high concentration (75 ppm) could be used as a control measure to protect forests and other lands from the invasion of M. micrantha.
Subject(s)
Mikania , Gene Expression Profiling , Gibberellins/pharmacology , Mikania/genetics , Mikania/metabolism , Plant Growth Regulators/metabolism , Plant Growth Regulators/pharmacology , Plant Weeds/genetics , Plant Weeds/metabolismABSTRACT
Nineteen compounds were isolated and structurally characterized from an ethanol extract of Dendrobium gratiossimum, including dendrogratiol A(1), DDB-1(2), 3,4-dihydroxyl-5,3',4'-trimethoxybibenzyl(3), amoenylin(4), chrysotoxine(5), DTB(6), 3,4,4'-trihydroxyl-5,3'-dimethoxybenzyl(7), 3-methylgiga(8), aloifol(9), gigantol tetramethyl ether(10), batatasin â ¢(11), moscatilin(12), moniliformine(13), gigantol(14), DMB(15), flavanthrinin(16), cannithrene-2(17), 3,4-dihydroxyl-5,4'-dimethoxystilbene(18) and 4-hydroxy-3,5,4'-trimethoxystilbene(19). 1 was a new compound, and 2-10, 16, 18 and 19 were obtained from this plant species for the first time. In vitro cytotoxic and antiviral activities of these isolates were evaluated, which displayed that 4 showed moderate cytotoxicity against human hepatoma cell line HepG2 with the IC_(50) of 10.15 µmol·L~(-1); 7 and 12 exhibited moderate inhibitory activity towards HIV virus with the IC_(50) of 9.35 and 9.15 µmol·L~(-1), respectively; and 10 displayed inhibitory activity against IAV virus with the IC_(50) of 8.90 µmol·L~(-1).
Subject(s)
Bibenzyls , Dendrobium , Bibenzyls/pharmacology , Cell Line , HumansABSTRACT
This study aimed to investigate the molecular mechanisms underlying the roles of metformin (MET) and Sorafenib (SOR) in the treatment of endometrial hyperplasia (EH) in polycystic ovary syndrome (PCOS). Effects of MET and SOR on the area of endometrium and myometrium were detected. Western blot analysis and immunohistochemistry assays were carried out to detect the levels of mammalian target of rapamycin complex 1 (mTORC1), mTORC2, LC3-II, P62, and Caspase-3 in rats and cultured cells. Furthermore, cell counting kit-8 assay and flow cytometry analysis was carried out to determine the apoptotic profiles of treated cells. MET and SOR could apparently decrease the areas of endometrium and myometrium in PCOS. MET notably enhanced the expression of LC3-II and Caspase-3 in PCOS while substantially reducing the level of mTORC1 and P62. Similarly, SOR also enhanced the expression of LC3-II and Caspase-3 in PCOS while substantially reducing the level of mTORC2 and P62. Treatment with MET and SOR significantly inhibited the proliferation of HCC-94 and HEC-1-A cells while promoting their apoptosis by upregulating the expression of Caspase-3. In cells treated with MET, the expression of mTORC1 and LC3-II was upregulated while the expression of P62 was downregulated. Similarly, in cells treated with SOR, the expression of mTORC2 and LC3-II was also upregulated while the expression of P62 was also downregulated. Furthermore, MET showed no effect on mTORC2 expression, while SOR showed no effect on mTORC1 expression. In this study, we suggested that MET and SOR alleviated the risk of EH in PCOS via the mTORC1/autophagy/apoptosis axis and mTORC2/autophagy/apoptosis axis, respectively.
Subject(s)
Apoptosis/drug effects , Autophagy/drug effects , Endometrial Hyperplasia/pathology , Metformin/pharmacology , Polycystic Ovary Syndrome/pathology , Sorafenib/pharmacology , Animals , Apoptosis Regulatory Proteins/drug effects , Apoptosis Regulatory Proteins/metabolism , Drug Synergism , Endometrial Hyperplasia/metabolism , Female , Polycystic Ovary Syndrome/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
An analytical method based on UFLC-QTRAP-MS/MS was established for simultaneous determination of thirty-three components including steroidal saponins, homoisoflavonoids, amino acids and nucleosides in Ophiopogonis Radix. Thirty-three target components of commercial medicinal materials of Maidong were comparative analysis. Synergi™ Hydro-RP 100î¦ column (2.0 mm × 100 mm, 2.5 µm) was used with 0.1% formic acid solution-0.1% formic acid acetonitrile for gradient elution at a flow rate of 0.4 mL·min⻹. In addition, multiple reaction monitoring (MRM) mode was employed. The data were comprehensively processed and analyzed with hierarchical clustering analysis(HCA), principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) methods. All components showed good linearity(r>0.999 0) within the tested ranges. The average recoveries were between 96.23%-102.0%, and the relative standard deviation(RSD) were less than 5%. The results showed that there were significant differences in components between Ophiopogonis Radix and Liriopes Radix, with seven components obviously different. This method was useful for providing basis for the comprehensive evaluation and intrinsic quality control of Ophiopogonis Radix and Liriopes Radix , and may provide a new method reference for the identification of Ophiopogonis Radix and Liriopes Radix.
Subject(s)
Drugs, Chinese Herbal/analysis , Liriope Plant/chemistry , Ophiopogon/chemistry , Saponins/analysis , Chromatography, High Pressure Liquid , Phytochemicals/analysis , Plant Roots/chemistry , Tandem Mass SpectrometryABSTRACT
An analytical method based on UFLC-QTRAP-MS/MS was developed for simultaneous determination of fifteen components including eleven lignans (schizantherin B, schisandrol B, schizandrin C, γ-schisandrin, deoxyschizandrin, schisantherin, schisandrin, schisanhenol, gomisin D, gomisin J, and angeloylgomisin H) and organic acids (S)-malic acid, D(-)-tartaric acid, protocatechuic acid, and quinic acid) in Schisandrae Chinensis Fructus. Samples from different product specifications were evaluated and analyzed. The chromatographic separation was performed on a Synergi™ Hydro-RP 100Å column (2.0 mm×100 mm, 2.5 µm) at 40 °C with a gradient elution by employing 0.1% aqueous formic acid (A)-acetonitrile (B) as the mobile phase, and the flow rate was 0.4 mL·min⻹, using an electrospray ionization (ESI) source and multiple reaction monitoring (MRM) mode. Fifteen components were evaluated synthetically by TOPSIS and gray related degree. The results showed that fifteen components had good linearity (r>0.999 90), and the limits of detection were all satisfactory. The average recoveries of standard addition for the compounds were between 95.42 % and 98.86 %, and the relative standard deviations were less than 5%. The greatest difference of ri in grey related degree was 58.1%, whilst the greatest difference of Ci value in TOPSIS method was 94.8%. The results of these two methods showed that the holistic quality of No. 14 sample was the best. The developed method was accurate and reliable, which was suitable for the simultaneous determination of multiple functional substances and able to provide a new basis for the comprehensive assessment and overall control of the quality of Schisandrae Chinensis Fructus.
Subject(s)
Drugs, Chinese Herbal/analysis , Lignans/analysis , Schisandra/chemistry , Chromatography, High Pressure Liquid , Quality Control , Tandem Mass SpectrometryABSTRACT
BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease featured by memory loss, neuroinflammation and oxidative stress. Overproduction or insufficient clearance of Aß leads to its pathological aggregation and deposition, which is considered the predominant neuropathological hallmark of AD. Therefore, reducing Aß levels and inhibiting Aß-induced neurotoxicity are feasible therapeutic strategies for AD treatment. Wolfberry has been traditionally used as a natural antioxidant and anti-aging product. However, whether wolfberry species has therapeutic potential on AD remains unknown. METHOD: The effects of fruitless wolfberry-sprout extract (FWE) on Aß fibrillation and fibril disaggregation was measured by thioflavin T fluorescence and transmission electron microscope imaging; Aß oligomer level was determined by dot-blot; Cell viability and apoptosis was assessed by MTT and TUNEL assay. The levels of Aß40/42, oxidative stress biomarkers and inflammatory cytokines were detected by corresponding kits. 8-month-old male APP/PS1 mice and their age-matched WT littermates were treated with FWE or vehicle by oral administration (gavage) once a day for 4 weeks. Then the cognitive performance was determined using object recognition test and Y-maze test. The Aß burden and gliosis was evaluated by immunostaining and immunoblotting, respectively. RESULTS: FWE significantly inhibited Aß fibrillation and disaggregated the formed Aß fibrils, lowered Aß oligomer level and Aß-induced neuro-cytotoxicity, and attenuated oxidative stress in vitro. Oral administration of FWE remarkably improved cognitive function, reduced Aß burden, decreased gliosis and inflammatory cytokines release, and ameliorated oxidative stress in the brains of APP/PS1 mice. CONCLUSION: These findings indicate that FWE is a promising natural agent for AD treatment.
Subject(s)
Alzheimer Disease/complications , Cognition Disorders/drug therapy , Cognition Disorders/etiology , Lycium/chemistry , Plant Extracts/therapeutic use , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/genetics , Animals , Brain/metabolism , Brain/pathology , Calcium-Binding Proteins/metabolism , Disease Models, Animal , Glial Fibrillary Acidic Protein/metabolism , Glutathione/metabolism , Glutathione Disulfide/metabolism , Interleukin-6/metabolism , Maze Learning/drug effects , Mice , Mice, Inbred C57BL , Mice, Transgenic , Microfilament Proteins/metabolism , Mutation/genetics , Oxidative Stress/drug effects , Peptide Fragments/metabolism , Presenilin-1/genetics , Recognition, Psychology/drug effects , Superoxide Dismutase/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
BACKGROUND: As the key component of glutathione peroxidase with unique antioxidant properties, selenium has been considered to play an important part on lipid metabolism. However, the associations of serum selenium concentrations with lipid concentrations and dyslipidemia are still controversial. METHODS: We analyzed cross-sectional data including serum selenium levels, lipid concentrations and other related indexes of 8198 rural Chinese. Serum selenium was measured by inductively coupled plasma mass spectrometry, and total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-c) and low density lipoprotein-cholesterol (LDL-c) of serum were measured with kits. RESULTS: Overall, mean serum selenium was 120 µg/l. Multivariate liner regression revealed that selenium concentrations were positively correlated with TC (P < 0.001), HDL-c (P < 0.001), TG (P < 0.001) and LDL-c (P < 0.001). Compared with the lowest quintile of serum selenium, participants in quintile 3, 4 and 5 had higher risks of High-TC dyslipidemia (P ≤ 0.02) and High-LDLC dyslipidemia (P < 0.02) after adjusting for covariates. In the stratified analyses, we found that the selenium-dyslipidemia associations were significantly stronger in post-menopausal women (OR: 2.72; 95% CI: 1.97, 4.17) and diabetics (OR: 9.40; 95% CI: 3.02, 29.26). CONCLUSION: Elevated serum selenium levels were correlated with the increased concentrations of TC, LDL-c, HDL-c and TG, and increased the risk of High-TC and High-LDLC dyslipidemia among rural Chinese. However, the real associations between serum selenium and lipid profile should be verified in specifically designed randomized trials in future.
Subject(s)
Dyslipidemias/blood , Lipids/blood , Selenium/blood , China , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cross-Sectional Studies , Female , Humans , Lipid Metabolism , Male , Middle Aged , Rural Population , Triglycerides/bloodABSTRACT
An analytical method based on UFLC-QTRAP-MS/MS was established for simultaneous determination of thirty-three components including steroidal saponins, homoisoflavonoids, amino acids and nucleosides in Ophiopogonis Radix. Thirty-three target components of commercial medicinal materials of Maidong were comparative analysis. Synergi™ Hydro-RP 100 column (2.0 mm × 100 mm, 2.5 μm) was used with 0.1% formic acid solution-0.1% formic acid acetonitrile for gradient elution at a flow rate of 0.4 mL·min⁻¹. In addition, multiple reaction monitoring (MRM) mode was employed. The data were comprehensively processed and analyzed with hierarchical clustering analysis(HCA), principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) methods. All components showed good linearity(>0.999 0) within the tested ranges. The average recoveries were between 96.23%-102.0%, and the relative standard deviation(RSD) were less than 5%. The results showed that there were significant differences in components between Ophiopogonis Radix and Liriopes Radix, with seven components obviously different. This method was useful for providing basis for the comprehensive evaluation and intrinsic quality control of Ophiopogonis Radix and Liriopes Radix , and may provide a new method reference for the identification of Ophiopogonis Radix and Liriopes Radix.
Subject(s)
Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Liriope Plant , Chemistry , Ophiopogon , Chemistry , Phytochemicals , Plant Roots , Chemistry , Saponins , Tandem Mass SpectrometryABSTRACT
Grossamide, a representative lignanamide in hemp seed, has been reported to possess potential anti-inflammatory effects. However, the potential anti-neuroinflammatory effects and underlying mechanisms of action of grossamide are still unclear. Therefore, the present study investigated the possible effects and underlying mechanisms of grossamide against lipopolysaccharide (LPS)-induced inflammatory response in BV2 microglia cells. BV2 microglia cells were pre-treated with various concentrations of grossamide before being stimulated with LPS to induce inflammation. The levels of pro-inflammatory cytokines were determined using the enzyme-linked immunoassay (ELISA) and mRNA expression levels were measured by real-time PCR. The translocation of nuclear factor-kappa B (NF-κB) and contribution of TLR4-mediated NF-κB activation on inflammatory effects were evaluated by immunostaining and Western blot analysis. This study demonstrated that grossamide significantly inhibited the secretion of pro-inflammatory mediators such as interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), and decreased the level of LPS-mediated IL-6 and TNF-α mRNA. In addition, it significantly reduced the phosphorylation levels of NF-κB subunit p65 in a concentration-dependent manner and suppressed translocation of NF-κB p65 into the nucleus. Furthermore, grossamide markedly attenuated the LPS-induced expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). Taken together, these data suggest that grossamide could be a potential therapeutic candidate for inhibiting neuroinflammation in neurodegenerative diseases.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Cannabis/chemistry , Drugs, Chinese Herbal/pharmacology , Lipopolysaccharides/adverse effects , Microglia/drug effects , Animals , Cell Line , Cell Survival/drug effects , Cytokines/genetics , Cytokines/metabolism , Gene Expression Regulation/drug effects , Mice , Microglia/cytology , Microglia/immunology , Plant Extracts/pharmacology , Protein Transport/drug effectsABSTRACT
OBJECTIVE: To explore the regularity of distribution of press-sensitive acupoints on the body surface in tinnitus patients, so as to provide evidence for selecting suitable acupuncture points in the treatment of tinnitus. METHODS: Sixty-three cases of tinnitus patients (from 25 to 75 years in age) were recruited in the present study. The patient was asked to take a sitting, supine and prone position, successively, and the operator used the thumb to moderately press the subject's head, neck, back, four limbs below the knee- and elbow joints along the three Hand- and three Foot-yang and yin meridians. Those acupoints that appeared pressing pain, or soreness-distension, numbness, or radiation feeling more than 10 times were brought into the sequence analysis by using the Excel 2010. RESULTS: A total of 131 press-sensitive acupoints including 41 points with an appea-rance frequency of more than 10 times were found in the 63 tinnitus patients. These 41 acupoints distributing in the top three meri-dians were the Gallbladder Meridian of Foot-Shaoyang, Tri-energizer Meridian of Hand-Shaoyang and Spleen Meridian of Foot-Taiyin, and their involved regions were those below the knee-joints, bilateral sides of the head and marginal portion of the ear, sites bellow the elbow-joints, back-waist, successively in the appearance frequency. The top ten acupoints are Wangu (GB 12), Yifeng (SJ 17), Waiguan (SJ 5), Quchi (LI 11), Sanyinjiao (SP 6), Yanglingquan (GB 34), Fengchi (GB 20), Taichong (LR 3), Shousanli (LI 10) and Zulinqi (GB 41), in sequence. CONCLUSIONS: The press-sensitive acupoints in tinnitus patients distribute principally in the Gallbladder Meridian of Foot-Shaoyang, and below the knee-joint, and the most sensitive acupoints are Wangu (GB 12) and Yifeng (SJ 17). These findings may provide an objective basis for clinical diagnosis and treatment of tinnitus.
Subject(s)
Acupuncture Therapy , Tinnitus/therapy , Acupuncture Points , Adult , Aged , Female , Humans , Male , Meridians , Middle AgedABSTRACT
BACKGROUND AND PURPOSE: This trial evaluated the efficacy and safety of CT guided (125)I-seed implantation (CTII) plus chemotherapy with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment for locally recurrent rectal cancer (LRRC). MATERIAL AND METHODS: Patients with LRRC who received one prior chemotherapy regimen were enrolled and divided randomly assigned to FOLFORI alone (Arm A) and FOLFORI plus CTII (Arm B). The primary endpoint was local control time (LCT). Overall survival (OS) and treatment related adverse events (TRAEs) were also observed. RESULTS: Fifty-seven patients were enrolled from October 2008 and December 2014. Twenty-seven were assigned into Arm A and 30 into Arm B. The overall response rate of locally recurrent tumor was improved to 100% in Arm B versus 29.6% in Arm A (P<0.001). A significant longer LCT was observed in Arm A (P<0.001); median LCT was 12 months in Arm B versus 4 months in Arm A. A borderline significant improvement in OS was also observed in Arm B (P=0.0464); median OS was 25 months in Arm B versus 19 months in Arm A. For patients without distant metastases, median OS was 37 months in Arm B versus 21 months in Arm A (P=0.0101). For patients with (neo)adjuvant radiotherapy (ART), a longer LCT and OS were also found in Arm B (P<0.001 and P=0.0217, respectively). TRAEs were not serious generally. There was no statistically significant difference in treatment related toxicity between Arm A and B both for all patients and patients receiving ART. CONCLUSIONS: CTII plus FOLFIRI improves the LCT with tolerable toxicities as a second-line treatment in patients with local recurrent rectal cancer, and is helpful to prolong the OS, particularly in patients without distant metastases or with a history of radiotherapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Anus Neoplasms/radiotherapy , Brachytherapy/methods , Iodine Radioisotopes/therapeutic use , Neoplasm Recurrence, Local/radiotherapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Anus Neoplasms/diagnostic imaging , Anus Neoplasms/drug therapy , Brachytherapy/adverse effects , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Combined Modality Therapy , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Iodine Radioisotopes/adverse effects , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/drug therapy , Radiotherapy, Image-Guided/adverse effects , Radiotherapy, Image-Guided/methods , Survival Analysis , Tomography, X-Ray Computed , Treatment Outcome , Young AdultABSTRACT
Hemp seed is known for its content of fatty acids, proteins, and fiber, which contribute to its nutritional value. Here we studied the secondary metabolites of hemp seed aiming at identifying bioactive compounds that could contribute to its health benefits. This investigation led to the isolation of 4 new lignanamides, cannabisin M (2), cannabisin N (5), cannabisin O (8), and 3,3'-demethyl-heliotropamide (10), together with 10 known lignanamides, among which 4 was identified for the first time from hemp seed. Structures were established on the basis of NMR, HR-MS, UV, and IR as well as by comparison with the literature data. Lignanamides 2, 7, and 9-14 showed good antioxidant activity, among which 7, 10, and 13 also inhibited acetylcholinesterase in vitro. The newly identified compounds in this study add to the diversity of hemp seed composition, and the bioassays implied that hemp seed, with lignanamides as nutrients, may be a good source of bioactive and protective compounds.
Subject(s)
Antioxidants/pharmacology , Cannabis/chemistry , Cholinesterase Inhibitors/pharmacology , Phenols/chemistry , Phenols/pharmacology , Seeds/chemistry , Ethanol , Models, Molecular , Molecular Structure , Plant Extracts/chemistry , Pyrrolidines/chemistry , Pyrrolidines/pharmacokineticsABSTRACT
To investigate the secondary metabolites of endophytic fungi Pericinia sp. F-31. Column chromatography on silica gel, Sephadex LH-20 and semi-preparative HPLC were used to separate and purify the compounds. Two compounds were isolated from the fermentation broth of Periconia sp. Their structures were identified as 5-(1-hydroxyhexyl) -6-methyl-2H-pyran-2-one (1) and 2-(3-hydroxy-4-methylphenyl) -propanoic acid (2). Compound 1 was a new lactone compound, compound 2 was new natural product, and the NMR data of compound 2 was reported for the first time.
Subject(s)
Annona/microbiology , Ascomycota/metabolism , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Endophytes/metabolism , Lactones/chemistry , Lactones/isolation & purification , Ascomycota/chemistry , Ascomycota/genetics , Ascomycota/isolation & purification , Drugs, Chinese Herbal/metabolism , Endophytes/chemistry , Endophytes/genetics , Endophytes/isolation & purification , Lactones/metabolism , Mass Spectrometry , Molecular StructureABSTRACT
Background. Sciatica is one of the most frequently reported complaints; it affects quality of life and reduces social and economic efficacy. Clinical studies on the efficacy of acupuncture therapy in sciatica are increasing, while systematic reviews assessing the efficacy of acupuncture therapy are still lacking. Objective. This study aims to assess the effectiveness of acupuncture therapy for sciatica. Methods. Comprehensive searches of 8 databases were conducted up until April 2015. Outcomes included effectiveness (proportion of patients who improved totally or partly in clinical symptoms), pain intensity, and pain threshold. Effect sizes were presented as risk ratio (RR) and mean difference (MD). Pooled effect sizes were calculated by fixed effects or random effects model. Results. A total of 12 studies (involving 1842 participants) were included. Results showed that acupuncture was more effective than conventional Western medicine (CWM) in outcomes effectiveness (RR 1.21, 95% CI: 1.16-1.25), pain intensity (MD -1.25, 95% CI: -1.63 to -0.86), and pain threshold (MD: 1.08, 95% CI: 0.98-1.17). Subgroup and sensitivity analysis found that the results did not change in different treatment method and drug categories substantially. The reported adverse effects were acceptable. Conclusions. Acupuncture may be effective in treating the pain associated with sciatica.
ABSTRACT
A rapid and efficient method was established for the simultaneous determination of structures and configurations for 45 phenolics isolated from crude red grape skin extracts without extensive sample preparation. Separation and compound assignments were achieved using high performance liquid chromatography coupled to diode array detection and tandem mass spectrometry (HPLC-DAD-MS(2)). A Poroshell 120 EC-C18 (100mm×3.0mm, 2.7µm) column was employed to separate the phenolics, which were eluted using a gradient of acetonitrile and water acidified with 0.2% formic acid. Phenolics were identified by comparison of their UV-vis spectra, mass spectra and MS(2) data with those in the literature. Using this procedure, five compounds were detected for the first time in Vitis amurensis. Good separation of most phenolics was achieved in 26min. The methods described here can be used for the characterization of phenolics in a variety of grapes and grape products.
Subject(s)
Phenols/analysis , Vitis/chemistry , Chromatography, High Pressure Liquid/methods , Plant Extracts/chemistry , Tandem Mass Spectrometry/methodsABSTRACT
PURPOSE: We intended to evaluate the superiority of cisplatin-based chronotherapy in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and investigate the relationship between the circadian rhythm and the variability of pharmacokinetics for cisplatin. METHODS: Forty-one patients with advanced NSCLC were divided into two groups with minimization randomization, including routine group (24 cases) and chronotherapy group (17 cases). The clinical effect and toxicity between the two groups were investigated. The population pharmacokinetics of cisplatin was calculated using nonlinear mixed-effects modeling method. RESULTS: There is no significant difference in total response rate between chronotherapy group (52.94%) and routine chemotherapy group (50.00%), p = 0.853. The rate of leucopenia (grade 3 or 4) in chronotherapy group (11.76%) is significantly lower than that in routine chemotherapy (37.50%), p < 0.05. The rate of neutropenia (grade 3 or 4) in chronotherapy group (11.76%) is significantly lower than that in routine chemotherapy group (33.33%), p < 0.05. The proportion of gastrointestinal toxicity (nausea, grade 1 vs 2) in chronotherapy group is significantly lower than that in routine chemotherapy, p < 0.05. When cisplatin was administered at 18:00, the CL was 1.38- and 1.22-fold higher than those administered at 6:00 for total and unbound cisplatin, respectively (p < 0.05). CONCLUSIONS: Cisplatin-based chronotherapy has advantage in relieving side effects of chemotherapy, and circadian could influence the metabolism of cisplatin, and more clinical researches are needed.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Cisplatin/pharmacokinetics , Lung Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cisplatin/administration & dosage , Cisplatin/adverse effects , Drug Chronotherapy , Female , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm StagingABSTRACT
To investigate the secondary metabolites of endophytic fungi Pericinia sp. F-31. Column chromatography on silica gel, Sephadex LH-20 and semi-preparative HPLC were used to separate and purify the compounds. Two compounds were isolated from the fermentation broth of Periconia sp. Their structures were identified as 5-(1-hydroxyhexyl) -6-methyl-2H-pyran-2-one (1) and 2-(3-hydroxy-4-methylphenyl) -propanoic acid (2). Compound 1 was a new lactone compound, compound 2 was new natural product, and the NMR data of compound 2 was reported for the first time.