ABSTRACT
Filter-free wavelength-selective photodetectors have garnered significant attention due to the growing demand for smart sensors, artificial intelligence, the Internet of Everything, and so forth. However, the challenges associated with large-scale preparation and compatibility with complementary metal-oxide-semiconductor (CMOS) technology limit their wide-ranging applications. In this work, we address the challenges by constructing vertically stacked graded-band-gap zinc-tin oxide (ZTO) thin-film transistors (TFTs) specifically designed for wavelength-selective photodetection. The ZTO thin films with various band gaps are fabricated via atomic layer deposition (ALD) by varying the ALD cycle ratios of zinc oxide (ZnO) and SnO2. The ZTO film with a small Sn ratio exhibits a decreased band gap, and the resultant TFT shows a degraded performance, which can be attributed to the Sn4+ dopant introducing a series of deep-state energy levels in the ZnO band gap. As the ratio of Sn increases further, the band gap of the ZTO also increases, and the mobility of the ZTO TFT increases up to 30 cm2/V s, with a positive shift of the threshold voltage. The photodetectors employing ZTO thin films with distinct band gaps show different spectral responsivities. Then, vertically stacked ZTO (S-ZTO) thin films, with gradient band gaps increasing from the bottom to the top, have been successfully deposited using consecutive ALD technology. The S-ZTO TFT shows decent performance with a mobility of 18.4 cm2/V s, a threshold voltage of 0.5 V, an on-off current ratio higher than 107, and excellent stability under ambient conditions. The resultant S-ZTO TFT also exhibits obviously distinct photoresponses to light at different wavelength ranges. Furthermore, a device array of S-ZTO TFTs demonstrates color imaging by precisely reconstructing patterned illuminations with different wavelengths. Therefore, this work provides CMOS-compatible and structure-compact wavelength-selective photodetectors for advanced and integrable optoelectronic applications.
ABSTRACT
Thanks to their excellent compatibility with the complementary metal-oxide-semiconductor (CMOS) process, antiferroelectric (AFE) HfO2/ZrO2-based thin films have emerged as potential candidates for high-performance on-chip energy storage capacitors of miniaturized energy-autonomous systems. However, increasing the energy storage density (ESD) of capacitors has been a great challenge. In this work, we propose the fabrication of ferroelectric (FE) Hf0.5Zr0.5O2/AFE Hf0.25Zr0.75O2 bilayer nanofilms by plasma-enhanced atomic layer deposition for high ESD capacitors with TiN electrodes. The effects of the FE/AFE thickness composition and annealing conditions are investigated, revealing that the Hf0.5Zr0.5O2 (1 nm)/Hf0.25Zr0.75O2 (9 nm) bilayer can generate the optimal ESD after optimized annealing at 450 °C for 30 min. This is mainly ascribed to the factor that the introduction of a 1 nm Hf0.5Zr0.5O2 layer enhances the formation of the tetragonal (T) phase with antiferroelectricity in the AFE Hf0.25Zr0.75O2 layer as well as the breakdown electric field of the bilayer while fixing the FE/AFE bilayer thickness at 10 nm. As a result, a ESD as high as 71.95 J cm-3 can be obtained together with an energy storage efficiency (ESE) of 57.8%. Meanwhile, with increasing the measurement temperature from 300 and 425 K, the capacitor also demonstrates excellent stabilities of ESD and ESE. In addition, superior electrical cycling endurance is also demonstrated. Further, by integrating the capacitor into deep silicon trenches, a superhigh ESD of 364.1 J cm-3 is achieved together with an ESE of 56.5%. This work provides an effective way for developing CMOS process-compatible, eco-friendly and superhigh ESD three-dimensional capacitors for on-chip energy storage applications.
ABSTRACT
Currently, therapies for ischemic stroke are limited. Ginkgolides, unique Folium Ginkgo components, have potential benefits for ischemic stroke patients, but there is little evidence that ginkgolides improve neurological function in these patients. Clinical studies have confirmed the neurological improvement efficacy of diterpene ginkgolides meglumine injection (DGMI), an extract of Ginkgo biloba containing ginkgolides A (GA), B (GB), and K (GK), in ischemic stroke patients. In the present study, we performed transcriptome analyses using RNA-seq and explored the potential mechanism of ginkgolides in seven in vitro cell models that mimic pathological stroke processes. Transcriptome analyses revealed that the ginkgolides had potential antiplatelet properties and neuroprotective activities in the nervous system. Specifically, human umbilical vein endothelial cells (HUVEC-T1 cells) showed the strongest response to DGMI and U251 human glioma cells ranked next. The results of pathway enrichment analysis via gene set enrichment analysis (GSEA) showed that the neuroprotective activities of DGMI and its monomers in the U251 cell model were related to their regulation of the sphingolipid and neurotrophin signaling pathways. We next verified these in vitro findings in an in vivo cuprizone (CPZ, bis(cyclohexanone)oxaldihydrazone)-induced model. GB and GK protected against demyelination in the corpus callosum (CC) and promoted oligodendrocyte regeneration in CPZ-fed mice. Moreover, GB and GK antagonized platelet-activating factor (PAF) receptor (PAFR) expression in astrocytes, inhibited PAF-induced inflammatory responses, and promoted brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) secretion, supporting remyelination. These findings are critical for developing therapies that promote remyelination and prevent stroke progression.
Subject(s)
Demyelinating Diseases , Diterpenes , Ischemic Stroke , Neuroprotective Agents , Stroke , Animals , Astrocytes/metabolism , Demyelinating Diseases/drug therapy , Demyelinating Diseases/metabolism , Diterpenes/pharmacology , Diterpenes/therapeutic use , Endothelial Cells , Ginkgo biloba , Ginkgolides/metabolism , Ginkgolides/pharmacology , Ginkgolides/therapeutic use , Humans , Lactones/pharmacology , Mice , Neuroprotective Agents/pharmacology , Stroke/drug therapy , Stroke/geneticsABSTRACT
The effect of paeoniflorin on apoptosis and cell cycle in human B-cell acute lymphoblastic leukemia(B-ALL) and its underlying mechanism were investigated in this study. Nalm-6 and SUP-B15 cells were cultured in vitro and divided into control group(0 µg·mL~(-1)) and experimental groups(200, 400, and 800 µg·mL~(-1) paeoniflorin). Cell counting kit-8(CCK-8) was used to measure the viability of Nalm-6 and SUP-B15 cells, and cell apoptosis and cell cycle distribution were analyzed by flow cytometry. Western blot was used to detect the protein levels of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase(cleaved PARP), c-Myc, and small ubiquitin-like modifier-specific protease 1(SENP1). The mRNA levels of c-Myc and SENP1 in acute lymphoblastic leukemia(ALL) patients were analyzed based on the Oncomine database. AutoDock was used for molecular docking to analyze the interaction of paeoniflorin with c-Myc and SENP1 proteins. RESULTS:: showed that paeoniflorin inhibited the viability of Nalm-6 and SUP-B15 cells in concentration and time-dependent manners. Compared with the control group, paeoniflorin significantly up-regulated the expression of apoptosis-related proteins cleaved caspase-3 and cleaved PARP to induce apoptosis, evidently increased the proportion of G_2/M phase cells and induced G_2/M phase arrest, and obviously down-regulated the expression of c-Myc and SENP1 proteins in Nalm-6 and SUP-B15 cells. The mRNA levels of c-Myc and SENP1 in ALL patients were higher than those in the normal cell. Molecular docking demonstrated that paeoniflorin had good binding to c-Myc and SENP1 proteins. In summary, paeoniflorin inhibits the proliferation of Nalm-6 and SUP-B15 cells by inducing apoptosis and G_2/M phase arrest, which may be related to the down-regulation of c-Myc and SENP1 proteins.
Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma , Signal Transduction , Apoptosis , Caspase 3/genetics , Caspase 3/metabolism , Cell Line, Tumor , Cell Proliferation , Cysteine Endopeptidases/metabolism , Cysteine Endopeptidases/pharmacology , Cysteine Endopeptidases/therapeutic use , Glucosides , Humans , Molecular Docking Simulation , Monoterpenes , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , RNA, MessengerABSTRACT
OBJECTIVE: To investigate the efficacy of Sijunzi decoction () on limb weakness in a rat model of spleen Qi deficiency (SQD), and to study its effect on mitophagy in skeletal muscle through adenosine monophosphate-activated protein kinase (AMPK) / unc-51 like autophagy activating kinase 1 (ULK1) signaling. METHODS: SQD model rats were produced by fasting combined with forced swimming method for 15 d. After model assessment, rats were randomly divided into four groups of 10 [low/middle/high (L/M/H) Sijunzi decoction dose groups and a normal saline (S) group]. Limb holding power (HP) and body mass (BM) were measured after 2 weeks of treatment. Following euthanasia, quadriceps femoris were dissected and myofiber and mitochondrial morphology were observed by transmission electron microscopy (TEM). Mitochondrial membrane potential (MMP), adenosine triphosphatase (ATP) and reactive oxygen species (ROS) levels were determined using colorimetric methods, and immunoblot analysis of Microtubule-associated protein light chain 3 (LC3) and Sequestosome 1 (p62) was performed to monitor mitophagy and AMPK/ULK1 signaling. RESULTS: Compared with control (C) group rats, in the S group, HP was reduced, the myofiber Z line was disordered, mitochondria were scattered, and numerous vacuoles and mitophagy were observed. MMP and ATP levels were reduced, ROS levels were elevated, and LC3B expression, and p-AMPKα (Thr172)/AMPKα, p-ULK1 (Ser555)/ULK1, and p-Raptor (Ser792)/Raptor ratios were increased, while p62 expression and p-mTOR (Ser2448)/mTOR and p-ULK1 (Ser757)/ULK1 ratios were decreased. After treatment, compared with the S group, HP was improved in M and H groups but not in the L group. Mitophagy was reduced in M, H and L groups but the Z line was disordered and vacuolization remained in the L group. ATP levels were elevated in M, H and L groups, and MMPs were elevat-ed in M and H groups but not in the L group. ROS levels were decreased in M, H and L groups, as were LC3B expression and p-Raptor (Ser792)/Raptor ratios, while p62 expression and p-mTOR (Ser2448)/mTOR and p-ULK1 (Ser757)/ULK1 ratios were increased in M and H groups but not in the L group. p-AMPKα (Thr172)/AMPKα and p-ULK1 (Ser555)/ULK1 ratios were decreased in M, H and L groups. CONCLUSIONS: Sijunzi decoction improved HP, possibly by inhibiting mitophagy via suppression of AMPK/ULK1 signaling. This restored mitochondrial morphology and improved oxidative phosphorylation, which contributed to recovery of limb weakness in SQD model rats.
Subject(s)
Qi , Spleen , Adenosine Monophosphate , Animals , Autophagy-Related Protein-1 Homolog/genetics , Drugs, Chinese Herbal , Protein Kinases , RatsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Diterpene Ginkgolides Meglumine Injection (DGMI) is made of extracts from Ginkgo biloba L, including Ginkgolides A, B, and K and some other contents, and has been widely used as the treatment of cerebral ischemic stroke in clinic. It can be learned from the "Compendium of Materia Medica" that Ginkgo possesses the effect of "dispersing toxin". The ancient Chinese phrase "dispersing toxin" is now explained as elimination of inflammation and oxidative state in human body. And it led to the original ideas for today's anti-oxidation studies of Ginkgo in apoptosis induced by optic nerve crush injury. AIM OF THE STUDY: To investigate the underlying molecular mechanism of the DGMI in retinal ganglion cells (RGCs) apoptosis. MATERIALS AND METHODS: TUNEL staining was used to observe the anti-apoptotic effects of DGMI on the adult rat optic nerve injury (ONC) model, and flow cytometry and hoechst 33,342 staining were used to observe the anti-apoptotic effects of DGMI on the oxygen glucose deprivation (OGD) induced RGC-5 cells injury model. The regulation of apoptosis and MAPKs pathways were investigated with Immunohistochemistry and Western blotting. RESULTS: This study demonstrated that DGMI is able to decrease the conduction time of F-VEP and ameliorate histological features induced by optic nerve crush injury in rats. Immunohistochemistry and TUNEL staining results indicated that DGMI can also inhibit cell apoptosis via modulating MAPKs signaling pathways. In addition, treatment with DGMI markedly improved the morphological structures and decreased the apoptotic index in RGC-5 cells. Mechanistically, DGMI could significantly inhibit cell apoptosis by inhibiting p38, JNK and Erk1/2 activation. CONCLUSION: The study shows that DGMI and ginkgolides inhibit RGCs apoptosis by impeding the activation of MAPKs signaling pathways in vivo and in vitro. Therefore, the present study provided scientific evidence for the underlying mechanism of DGMI and ginkgolides on optic nerve crush injury.
Subject(s)
Apoptosis/drug effects , Crush Injuries/drug therapy , Ginkgolides/pharmacology , Optic Nerve Injuries/drug therapy , Animals , Cell Line , Crush Injuries/pathology , Disease Models, Animal , Ginkgo biloba/chemistry , Ginkgolides/administration & dosage , Ginkgolides/chemistry , In Situ Nick-End Labeling , MAP Kinase Signaling System/drug effects , Male , Meglumine/administration & dosage , Optic Nerve Injuries/pathology , Rats , Rats, Sprague-Dawley , Retinal Ganglion Cells/drug effects , Retinal Ganglion Cells/pathologyABSTRACT
AbstractããChronic myeloid leukemia (CML) is a malignant myeloproliferative tumor which is originating from hematopoietic stem cells. Chemotherapy is the preferred made of treatment for the disease. However, in recent years, more and more patients have multidrug resistance (MDR) during treatment, which is the main cause of failure treatment, therefore, the search for effective reversal agents has important clinical significance. Traditional Chinese medicine derived reversal agents have the characteristics of multiple targets, low toxicity and high efficiency, which can reverse the drug resistance through different mechanisms, and the research potential is unlimited. In recent years, it has been widely concerned by scholars at home and abroad, especially the research on physcion, emodin, curcumin, matrine, gambogic acid, oridonin, ligustrazine, solanine and other monomers, which has made great advance. In this reviwe, the recent research advance on the reversal of MDR in chronic myeloid leukemia by Chinese medicine monomer is summarized briefly.
Subject(s)
Drug Resistance, Multiple , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Antineoplastic Agents , Drug Resistance, Neoplasm , Drugs, Chinese Herbal , Humans , Medicine, Chinese TraditionalABSTRACT
We monitored the type and content of airborne pollen in Haidian District, Beijing City from 2012 to 2016 by the gravity precipitation method, and analyzed the variety of pollen, peak distribution features and changes of its content, and discontinuous variation of concentration. Multiple time scale analysis was carried out for pollen concentration by the ensemble empirical mode decomposition method (EEMD). The relationship between pollen concentration and meteorological factors was analyzed. The results indicated that during the research period, the main types of airborne pollen changed. Woody plants such as Cupressaceae and Salicaceae instead of herbaceous plants contributed the most content of pollen. There was no significant change of the yearly peak distribution of pollen concentration. The concentration in recent five years reduced, while the concentration of herbaceous plants (such as Scolopacjdae) increased. During the statistics period, pollen concentration showed discontinuous changes in early April, late May and early August. Pollen concentration had the change cycle of quasi 2 d, quasi 51 d and quasi 128 d. Among all meteorological factors, temperature played a dominant role in driving the concentration, which may significantly rise during 16 to 18 â. The impact of temperature changes on the daily concentration may be delayed and continuous; it is often highly related to the concentration 2-7 d later. Sunshine duration and wind speed had the most significant impact on daily pollen concentration.
Subject(s)
Air Pollutants , Beijing , China , Cities , Environmental Monitoring , Meteorological Concepts , Pollen , SeasonsABSTRACT
BACKGROUND: Spleen qi deficiency (SQD), a syndrome based on traditional Chinese medicine (TCM) theory, is common in patients after radical gastrectomy. SQD manifests with chronic gastrointestinal disorders and systemic symptoms and is challenging to manage. Hou Gu Mi Xi (HGMX) is a dietary TCM formula for SQD. This study aims to evaluate the efficacy and safety of HGMX in patients with SQD who have undergone radical gastrectomy for gastric cancer. METHODS AND DESIGN: This study is a multicenter, randomized, double-blind, placebo-controlled trial. One hundred thirty patients with SQD who have undergone radical gastrectomy for gastric cancer will be assigned to receive either HGMX or placebo for 2 years. The main outcome will be changes in SQD symptoms assessed by the Spleen Qi Deficiency Symptoms Grading and Quantifying Scale. The secondary outcomes will be changes in quality of life assessed by the Short Form 36 scale, performance status as assessed by the Eastern Cooperative Oncology Group Performance Status scale, body weight, and body mass index. Progression-free survival will also be assessed as a secondary outcome. Adverse events (AEs), severe AEs, and study withdrawal due to AEs will be recorded to evaluate the safety of HGMX. DISCUSSION: The results of this trial will provide initial evidence for the use of HGMX as an alternative and complementary intervention to manage chronic postoperative complications in patients who have undergone radical gastrectomy for gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03025152 . Registered on 17 January 2017.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Gastrectomy/adverse effects , Medicine, Chinese Traditional , Postoperative Complications/drug therapy , Qi , Stomach Neoplasms/surgery , Adult , Aged , Double-Blind Method , Drugs, Chinese Herbal/adverse effects , Humans , Middle Aged , Multicenter Studies as Topic , Outcome Assessment, Health Care , Randomized Controlled Trials as TopicABSTRACT
Two new labdane diterpenoids, Leojaponin E (1) and F (2), together with three known compounds were isolated from the dried herb of Leonurus japonicus Houtt., Lamiaceae. Their structures were determined based on extensive spectroscopic analyses. The absolute configurations of 1 and 2 were elucidated on the basis of experimental and calculated electronic circular dichroism spectra. In addition, compounds 1 and 2 exerted inhibition of LPS-induced PGE2 production in a dose-dependent manner at concentrations ranging from 5 to 20 µM.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Diterpenes/chemistry , Diterpenes/pharmacology , Leonurus/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Circular Dichroism , Dinoprostone/biosynthesis , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Lipopolysaccharides/pharmacology , Magnetic Resonance Spectroscopy , Mice , Molecular Structure , Plant Components, Aerial/chemistry , RAW 264.7 CellsABSTRACT
A new compound(Z)-6-hydroxy-4-methoxy-5,7-dimethylaurone was isolated from Cleistocalyx operculatus flower buds. Its structure was identified by spectroscopic data including MS, ¹H-NMR, ¹³C-NMR HSQC and HMBC. A known compound, 2',4'-dihydroxy-6'-methoxy-3'5'-dimethylchalcone (DMC), was also isolated and identified,and used as material to synthesize (Z)-6-hydroxy-4-methoxy-5,7-dimethylaurone.Anti-inflammatory activities of the two compounds were tested in vitro. The results showed that (Z)-6-hydroxy-4-methoxy-5,7-dimethylaurone possesses much stronger PGE2 inhibitory activity (IC50 6.12 nmol·L⻹) than the positive control ibuprofen ï¼68.66 nmol·L⻹ï¼.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Benzofurans/pharmacology , Flowers/chemistry , Syzygium/chemistry , Anti-Inflammatory Agents/isolation & purification , Benzofurans/isolation & purification , Chalcones , Dinoprostone/antagonists & inhibitorsABSTRACT
To study the metabolic transformation of pumiloside by rat intestinal flora in vitro and identify its metabolites. Pumiloside was incubated in the rat intestinal flora in vitro. HPLC was used to monitor the metabolic process, and HPLC-Q-TOF-MS was used to identify the structures of biotransformation products. In vitro, pumiloside was easily metabolized by rat intestinal flora, and with the prolongation of metabolic time, pumiloside was transformed into several metabolites. Three metabolites were initially identified in this experiment. The study indicated that pumiloside could be extensively metabolized in the rat intestinal flora in vitro.
Subject(s)
Bacteria/metabolism , Camptothecin/analogs & derivatives , Gastrointestinal Microbiome , Animals , Biotransformation , Camptothecin/metabolism , Chromatography, High Pressure Liquid , Intestines/microbiology , RatsABSTRACT
To discuss the synergistic mechanism of compatible use of two medicinal herbs,Panax notoginseng and Bletilla striata, an HPLC was established to determine two ginseng saponins (20S)-ginseng saponin Rg3 and ginseng saponin Rh4 contained in single decoction of Panax notoginseng as well as in compound decoction of Panax notoginseng and Bletillastriata in different compatibility ratio (1â¶0.5, 1â¶1, 1â¶2), followed by analyzing the impact of amount of notoginsenosides after compatibility. As a result, compared with the single decoction of Panax notoginseng, the contents of ginseng saponin Rg3 and ginseng saponin Rh4 in the compound decoction of Panax notoginseng and Bletillastriata were on the rise as the increasement of the amount of Bletillastriata. The contents of the notoginsengsaponin R1, ginseng saponin Rg1 and ginseng saponin Rb1 of Panax notoginseng single decoction were significantly decreased after compatibility. Therefore, after compatibility, it was more easy to produce (20S)-ginseng saponin Rg3 and ginseng saponin Rh4.This study can extend to a method of preparation of (20S)-ginseng saponin Rg3 and ginseng saponin Rh4. Furthermore, after compatibility, two ginseng saponins which had lipase inhibitory effect were both increased significantly, indicating that the compatibility of these two herb medicines may have effect on losing weight.
Subject(s)
Drugs, Chinese Herbal/analysis , Orchidaceae/chemistry , Panax notoginseng/chemistry , Saponins/analysis , Chromatography, High Pressure Liquid , Plant Roots/chemistry , Plants, MedicinalABSTRACT
CONTEXT: Strictosamide is the main representative constituent of Nauclea officinalis Pierre ex Pitard (Rubiaceae), which has been used for a long time in China to treat diseases related to infection and inflammation, but its pharmacological activities are not well studied. OBJECTIVE: This work evaluates the anti-inflammatory and analgesic activities of strictosamide by in vivo experiments. MATERIALS AND METHODS: The anti-inflammatory activity was assessed in mice by models of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema, acetic acid-elevated vascular permeability, and carboxymethylcellulose sodium (CMC-Na)-induced leukocyte migration. The analgesic activity was estimated in mice using acetic acid-induced writhing and hot-plate tests. Compound was injected to mice twice a day for 3 d at doses of 10, 20, and 40 mg/kg. RESULTS: At 20 and 40 mg/kg, strictosamide obviously decreased the TPA-induced mice ear edema (24.7 and 28.1% inhibition, respectively), and significantly inhibited acetic acid-stimulated peritoneal vascular permeability in mice (23.3 and 33.4% inhibition, respectively). It also significantly decreased the leukocytes in the mice peritoneal cavity induced by CMC-Na at all the tested doses (46.0, 49.1, and 58.7% inhibition, respectively). To acetic acid-induced writhing test in mice, strictosamide markedly prolonged the pain latency at 20 and 40 mg/kg and decreased the writhing counts at 40 mg/kg (49.7% inhibition). However, it did not obviously improve the pain threshold of mice in hot-plate test. DISCUSSION AND CONCLUSION: Strictosamide may have important effects on inflammation and inflammatory pain. The results provide scientific support for the role of strictosamide in the use of N. officinalis to treat inflammatory diseases.
Subject(s)
Analgesics/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Edema/drug therapy , Plant Extracts/therapeutic use , Vinca Alkaloids/therapeutic use , Analgesics/isolation & purification , Animals , Anti-Inflammatory Agents/isolation & purification , Edema/metabolism , Edema/pathology , Female , Male , Mice , Mice, Inbred ICR , Plant Extracts/isolation & purification , Vinca Alkaloids/isolation & purificationABSTRACT
AIM: To identify the structure of the acid-catalyzed product of strictosamide and explore the reaction mechanism. METHODS: The acid-catalyzed reaction process of strictosamide was monitored by HPLC, and a macroporous resin was used to purify the reaction solution. The structure of the product was confirmed by MS, NMR, and ROESY spectra. RESULTS: The acid-catalyzed transformation yield from strictosamide to vincoside lactam was 52%. CONCLUSION: The reaction mechanism of the transformation from strictosamide to vincoside lactam may be related to the stability of the three-dimensional configuration of the compound. These results offer a new way to obtain vincoside lactam from the widely distributed indole alkaloid strictosamide by acid-catalysis.
Subject(s)
Acids/chemistry , Lactams/chemistry , Vinca Alkaloids/chemistry , Catalysis , Molecular StructureABSTRACT
OBJECTIVE: To investigate the effect of Yisui Shengxue Granule (, YSSXG), a complex Chinese medicine, on the oxidative damage of erythrocytes from patients with hemoglobin H (HbH) disease. METHODS: Twenty-two patients with HbH disease and 22 healthy volunteers were observed. YSSXG was given to patients with HbH disease for 3 months. Before and after the 3-month treatment, blood parameters [hemoglobin (Hb), red blood cells (RBCs), and reticulocyte percent (Ret)] were examined; inclusion bodies in erythrocytes were observed by transmission electron microscopy (TEM); activities of antioxidant defense enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (Cat)] and erythrocyte membrane malondialdehyde (MDA) concentrations were determined. RESULTS: In patients with HbH disease, measured values of RBC and Hb obtained from the first to the third months after treatment with YSSXG were significantly higher than before treatment (P<0.01). Measured values of Ret from the second to the third months after treatment were significantly lower than before treatment (P<0.05 and P<0.01, respectively). Prior to treatment with YSSXG, TEM images of RBCs showed the presence of numerous inclusion bodies. After treatment with YSSXG, the amount and volume of inclusion bodies decreased. Treatment with YSSXG also led to a significant increase in SOD activity (P<0.01), a decrease in Cat activity (P<0.01), and no significant differences in GSHPx activity (P>0.05) or MDA concentration (P>0.05). However, compared with the healthy counterparts, SOD, GSH-Px, and Cat activities presented at high levels (P<0.01) both before and after treatment. CONCLUSIONS: YSSXG could improve the degree of hemolysis and anemia in patients with HbH disease. The mechanism may be related to its antioxidative effects, which could elevate the activity of total SOD in erythrocytes and efficiently inhibit the oxidative precipitation of ß-globin chains.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Erythrocytes/drug effects , Erythrocytes/pathology , Oxidative Stress/drug effects , alpha-Thalassemia/blood , alpha-Thalassemia/pathology , Adolescent , Adult , Catalase/metabolism , Child , Child, Preschool , Drugs, Chinese Herbal/therapeutic use , Erythrocyte Membrane/drug effects , Erythrocyte Membrane/metabolism , Erythrocyte Membrane/ultrastructure , Erythrocytes/enzymology , Erythrocytes/ultrastructure , Female , Glutathione Peroxidase/metabolism , Humans , Inclusion Bodies/drug effects , Inclusion Bodies/ultrastructure , Male , Malondialdehyde/metabolism , Superoxide Dismutase/metabolism , Young Adult , alpha-Thalassemia/drug therapyABSTRACT
A pilot study was conducted to test an membrane bioreactor (MBR) process for combined biological and chemical P removal to achieve a very low effluent total phosphorus (TP) concentration of 0.025 mg P/L. With the data from the pilot test, a simulation study was performed to demonstrate that: (1) the pilot system behaviour (effluent quality, MLSS, etc.) can be modelled accurately with an activated sludge model combined with a chemical precipitation model; and (2) with the calibrated model, simulation scenarios can be performed to further understand the pilot MBR process, and provide information for optimizing design and operation when applied at full-scale. Results from the pilot test indicated that the system could achieve very low effluent TP concentration through biological P removal with a limited chemical addition, and chemical addition to remove P to very low level did not affect other biological processes, i.e., organic and nitrogen removal. Simulation studies indicate that the process behaviour can be modelled accurately with an activated sludge model combined with a chemical precipitation model, and the calibrated model can be used to provide information to optimize system design and operation, e.g., chemical addition control under dynamic loading conditions is important for maintaining biological P removal.
Subject(s)
Bioreactors/microbiology , Membranes, Artificial , Sewage/microbiology , Waste Disposal, Fluid/methods , Water Purification/methods , Nitrogen/metabolism , Phosphorus/metabolismABSTRACT
OBJECTIVE: To observe the effects of Yiqi Huoxue Formula (YQHXF), a compound Chinese herbal medicine, on transforming growth factor-ß (TGF-ß)/smad signal transduction pathway and connective tissue growth factor (CTGF) in rats with renal interstitial fibrosis METHODS: Unilateral ureteral obstruction (UUO) rat model was established and the rats were randomly divided into 5 groups: untreated group, high-, medium-, and low-dose YQHXF groups and fosinopril sodium group. Another group with sham operation was set as control. All rats were administered with corresponding drugs for 3 weeks. After the last administration, each rat was sacrificed and weighed and the serum was separated for creatinine (Cr) and blood urea nitrogen (BUN) detection. Kidneys of the rats were taken out, and mRNA and protein expressions of TGF-ß, smad2, smad7 and CTGF were measured with real-time fluorescent quantitative reverse transcription-polymerase chain reaction and Western blotting respectively; fibrosis of the kidney tissue was observed with hematoxylin-eosin (HE) staining and Masson trichrome staining. RESULTS: Compared with sham-operation group, Cr and BUN in serum of UUO groups were increased, while high-dose YQHXF treatment decreased the UUO-induced increase of Cr and BUN levels. HE staining and Masson staining results showed that the renal tubular epithelial cells in untreated group got atrophied; lumens of renal tubules expanded; fibroplastic proliferation and inflammatory cell infiltration were observed in renal interstitium; the number of glomerulus decreased and collagen increased significantly compared with sham-operation group. In the high- and medium-dose YQHXF groups and fosinopril sodium group, the histopathological changes of inflammatory cell infiltration, fibroplastic proliferation, expansion of lumens of renal tubules was improved as compared with the untreated group. The mRNA and protein expressions of TGF-ß, smad2 and CTGF in untreated group were higher than those in sham-operation group (P<0.05), and the mRNA and protein expressions of smad7 in untreated group were lower than those in the sham-operation group (P<0.05). Compared with untreated group, high- and medium-dose of YQHXF significantly down-regulated the mRNA and protein expressions of TGF-ß, smad2 and CTGF (P<0.01, P<0.05), and up-regulated the mRNA and protein expressions of smad7 (P<0.01, P<0.05). CONCLUSIONS: The mRNA expression of CTGF in UUO rats may be regulated by TGF-ß/smad signaling transduction pathway. YQHXF might inhibit the expression of CTGF through down-regulation of TGF-ß and smad2 and up-regulation of smad7, thus inhibiting the progression of renal interstitial fibrosis.
Subject(s)
Connective Tissue Growth Factor/metabolism , Drugs, Chinese Herbal/pharmacology , Kidney Diseases/drug therapy , Signal Transduction , Smad Proteins/metabolism , Transforming Growth Factor beta/metabolism , Animals , Fibrosis , Kidney/metabolism , Kidney/pathology , Kidney Diseases/metabolism , Kidney Diseases/pathology , Male , Phytotherapy , Rats , Rats, Wistar , Smad2 Protein/metabolism , Smad7 Protein/metabolismABSTRACT
Ischemia-reperfusion (I/R) injury of the kidney is a complex pathophysiological process and a major cause of acute renal failure. It has been shown that I/R injury is related to inflammatory responses and activation of apoptotic pathways. Inhibition of certain elements of inflammatory responses and apoptotic pathway seemed to ameliorate renal I/R injury. As an effective element of Panax notoginseng, NR1 has antioxidant, anti-inflammatory, antiapoptotic, and immune-stimulatory activities. Therefore, we speculate that NR1 can attenuate renal I/R injury. Ischemia-reperfusion injury was induced by renal pedicle ligation followed by reperfusion along with a contralateral nephrectomy. Male Sprague-Dawley rats were randomized to four groups: sham group, I/R control group, NR1-1 group (rats treated with NR1, 20 mg.kg.d) and NR1-2 group (rats treated with NR1, 40 mg.kg.d). All animals were killed 72 h after I/R induction. Blood and renal tissues were collected. Renal dysfunction was observed by the level of serum creatinine and histological evaluation. Apoptosis and inflammatory response in the tissue of kidney were detected mainly with molecular biological methods. NR1 attenuated I/R-induced renal dysfunction as indicated by the level of serum creatinine and histological evaluation. It prevented the I/R-induced increases in the levels of proinflammatory cytokine TNF-alpha, myeloperoxidase activity, phosphorylation of p38, and activation of nuclear factor kappaB with cell apoptosis in the kidney and enhanced expression of antiapoptosis cytokine bcl-2. Treatment with NR1 improves renal function after I/R associated with a significant reduction in cell apoptosis and inflammatory responses, which may be related to p38 and nuclear factor kappaB inhibition.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Ginsenosides/therapeutic use , Kidney/blood supply , Reperfusion Injury/prevention & control , Animals , Apoptosis/drug effects , Creatinine/blood , Cytokines/blood , Drug Evaluation, Preclinical , Drugs, Chinese Herbal/pharmacology , Genes, bcl-2 , Ginsenosides/pharmacology , Kidney/pathology , Kidney/physiopathology , Male , NF-kappa B/metabolism , Neutrophils/enzymology , Peroxidase/analysis , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Random Allocation , Rats , Rats, Sprague-Dawley , Renal Circulation/drug effects , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
OBJECTIVE: To explore the relationship between syndromes of traditional Chinese medicine (TCM) and genetic background in patients with beta-thalassemia. METHODS: TCM syndromes were surveyed in the selected 78 patients with beta-thalassemia intermedia including 120 parents. The gene mutations were detected separately. The frequency and score of TCM syndromes between the offspring and their parents in different family types were analyzed, and the differences were compared. RESULTS: The 73 families were divided into two family types by hereditary characteristics. Family type one meant that genotypes of one of the parents were normal, while the offspring genotypes were heterozygous and were exactly the same as another parent. In the 22 families of type one, the heterozygous offspring manifested 6 high-frequency symptoms and signs such as spontaneous perspiration, dry mouth and dry throat, pale or sallow complexion, tidal fever and night sweating, lassitude and pale fingernails. The heterozygous parents manifested 5 high-frequency symptoms and signs such as lassitude in loins and knees, dizziness, aversion to cold and cold limbs, tinnitus, dry mouth and dry throat. The normal parents manifested 3 high-frequency symptoms and signs such as lassitude in loins and knees, dizziness, and spontaneous perspiration. TCM syndrome score in the heterozygous offspring was higher than that in the heterozygous and normal parents, but there was no significant difference (P>0.05). Family type two meant that genotypes of both parents were heterozygous, while the offspring genotypes were heterogenic duplex heterozygotes. In the 51 families of type two, the offspring manifested 9 high-frequency symptoms and signs such as pale or sallow complexion, spontaneous perspiration, dry mouth and dry throat, pale fingernails, tidal fever and night sweating, lassitude, frequent attack of common cold, dysphoria with feverish sensation in chest, and yellow discoloration of the skin and sclera. The parents manifested 3 high-frequency symptoms and signs such as lassitude in loins and knees, dizziness, aversion to cold and cold limbs. TCM syndrome score in the offspring was significant higher than that in the parents (P<0.01). CONCLUSION: In the two family types, TCM syndrome in the offspring is of yin-blood deficiency, while the syndrome of the parents is of kidney deficiency. The differences of TCM syndromes between the offspring and the parents may have some relations to the type of mutant genes and genetically modified ingredients. This research provides scientific evidence to TCM syndrome differentiation treatment of thalassemia.