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ObjectiveTo explore the molecular mechanism of Sanhuang Xiexintang （SHXXT） in protecting stress gastric ulcer （SGU） in rats through network pharmacology， molecular docking， and animal experiments. MethodThe active ingredients and corresponding targets in SHXXT were collected and screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCMID）， Bioinformation Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and Swiss Target Prediction database. SGU-related targets were screened from the Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD）， GeneCards database， and PharmGKB database. Herbal-ingredient-target （H-C-T） network was constructed by using Cytoscape 3.9.1 software. Protein-protein interaction （PPI） of drug and disease intersection targets was analyzed by using the Protein Interaction Platform （STRING） database. Gene ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were conducted through the Database for Annotation Visualization and Integrated Discovery （DAVID）. The active ingredients and key targets were validated using AutodockVina 1.2.2 molecular docking software， and the experimental results were further validated through animal experiments. ResultThe 55 active ingredients were screened， and 255 potential target genes for SHXXT treatment of SGU were predicted. The PPI analysis showed that protein kinase B （Akt）， phosphatase and tensin homolog deleted on chromosome ten （PTEN）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and cyclooxygenase-2 （COX-2） are the core targets of SHXXT for protecting SGU. GO and KEGG analyses showed that SHXXT may affect the development of SGU by regulating various biological processes such as the phosphoinositide 3-kinase （PI3K）/Akt signaling pathway and inflammatory processes. The molecular docking results showed that both the active ingredients and key targets had good binding ability. Animal experiments showed that compared with the blank group， the ulcer index （UI） of the model group was significantly increased （P<0.01）， and the serum levels of TNF-α and IL-1β significantly increased （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly down-regulated （P<0.05）. The phosphorylation levels of PI3K， Akt， and nuclear factor kappa-B （NF-κB） were significantly up-regulated （P<0.05）. Compared with the model group， the UI of the treatment group was significantly reduced （P<0.01）， and the serum levels of TNF-α and IL-1β were significantly reduced （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly up-regulated （P<0.01）， and the phosphorylation levels of PI3K， Akt， and NF-κB were significantly downregulated （P<0.01）. ConclusionThe application of network pharmacology prediction， molecular docking simulation， and animal experimental validation confirms that SHXXT regulates the PI3K/Akt/NF-κB signaling pathway to regulate the inflammatory response of rats and thus protects the gastric mucosa of SGU rats.
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Itch is an unpleasant sensation that urges people and animals to scratch. Neuroimaging studies on itch have yielded extensive correlations with diverse cortical and subcortical regions, including the insular lobe. However, the role and functional specificity of the insular cortex (IC) and its subdivisions in itch mediation remains unclear. Here, we demonstrated by immunohistochemistry and fiber photometry tests, that neurons in both the anterior insular cortex (AIC) and the posterior insular cortex (PIC) are activated during acute itch processes. Pharmacogenetic experiments revealed that nonselective inhibition of global AIC neurons, or selective inhibition of the activity of glutaminergic neurons in the AIC, reduced the scratching behaviors induced by intradermal injection of 5-hydroxytryptamine (5-HT), but not those induced by compound 48/80. However, both nonselective inhibition of global PIC neurons and selective inhibition of glutaminergic neurons in the PIC failed to affect the itching-scratching behaviors induced by either 5-HT or compound 48/80. In addition, pharmacogenetic inhibition of AIC glutaminergic neurons effectively blocked itch-associated conditioned place aversion behavior, and inhibition of AIC glutaminergic neurons projecting to the prelimbic cortex significantly suppressed 5-HT-evoked scratching. These findings provide preliminary evidence that the AIC is involved, at least partially via aversive emotion mediation, in the regulation of 5-HT-, but not compound 48/80-induced itch.
Subject(s)
Humans , Animals , Serotonin , Insular Cortex , Pruritus/chemically induced , Cerebral Cortex/physiology , NeuronsABSTRACT
Cardiovascular diseases， with high incidence and high mortality， belong to the category of "chest impediment and heart pain" in traditional Chinese medicine （TCM）. Chinese medicines have unique effect on the prevention and treatment of cardiovascular diseases with little side effects. Huoxin pills， one of the National Essential Drugs， is formulated based on the basic pathogenesis of weak pulse at Yang and wiry pulse at Yin and the pathological basis of myocardial ischemia and hypoxia and used for treating angina pectoris of coronary heart disease （Qi deficiency and blood stasis syndrome）. This medicine is derived from the classic famous prescription and is composed of ten precious Chinese medicinal herbs. It can replenish Qi， activate blood， and warm collaterals to diffuse impediment by enhancing myocardial contractility and cardiac output to improve micro-circulation and increase coronary blood flow， regulating immune functions， alleviating inflammation， detoxifying， and tranquilizing mind. Clinically， it is suitable for patients with angina pectoris caused by the lack of heart Yang， chest tightness， shortness of breath， palpitation， fear of cold for limbs and so on， especially for the elderly with Yang deficiency or the patients with a history of myocardial infarction. On the basis of the available research reports， this paper explains the formula meaning of Huoxin pills from the perspective of the basic pathogenesis of coronary heart disease and predicts its action targets， location and links. Furthermore， we expound the mechanism of action of Huoxin pills based on basic research and clinical evidence-based research， aiming to provide data support and evidence for the clinical application of this medicine.
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Imperatorin, which is extracted from umbelliferous plants such as Radix Angelicae Dahuricae, Radix Saposhnikoviae and Fructus Cnidii, belongs to furanocoumarins and is especially rich in Radix Angelicae Dahuricae. Research has shown that imperatorin possesses functions of anti-inflammatory, analgesic, antibactrial, antiviral, antiallergic, anti-tumor, reverse drug resistance in tumor cells, interaction with drug metabolizing enzymes, affecting cardiovascular and nervous system effect. It is also one of the standard components in quality control of various analgesics. In recent years, research findings related to imperatorin is increasing fast. A number of patent applications have been approved for the application of imperatorin in the treatment of anti-tumor and cardiovascular diseases. In addition, since the water insolubility of imperatorin affects its bioavailability, most researchers have gradually attached importance to this aspect of research, such as modifying its structure or synthesizing its derivatives. The literatures on the pharmacological effects and mechanisms of imperatorin at home and abroad in recent years were consulted and summarized in this paper. Imperatorin was found not only to display other pharmacological effects like furanocoumarins but also could cure osteoporosis, skin diseases and show photosensitization. Moreover, the mechanism of its action has the effect of multi-pathway and multi-target, but most of the studies have not identified its targets, which still needs further study. Extensive and significant pharmacological effect make imperatorin show a great potential for development of new drugs. This paper reviews the basic properties, the progress on pharmacological effects and mechanisms of imperatorin, proposes the research status and direction of future reseach. Hopes to provide ideas for researchers and beneficial references for the future development and utilization of imperatorin.
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Objective:Explore the expression of SIRT1 protein in gastric cancer tissues and cells.Analyze the correlation of SIRT1 protein expression and multidrug resistance protein P-gp and Top-Ⅱ alpha.Methods:Immunohistochemical to detect SIRT1,P-gp and Top-Ⅱ alpha protein in 15 cases of gastric cancer tissue and 15 cases of normal gastric mucosa tissues.Western blot test the expression of SIRT1 protein in normal gastric mucosa epithelial cell line GES-1 and human gastric cancer cell line SGC7901,MKN45,MKN28,HGC27,AGS and MGC803.Western blot test the expression of SIRT1,P-gp and Top-Ⅱ alpha protein in normal gastric mucosa epithelial cell line GES-1 and human gastric cancer cell line SGC7901,MKN45.After siRNA-SIRT1/liposome transfection gastric cancer cells SGC7901,western blot test the changes of expression of SIRT1,P-gp and Top-Ⅱ alpha protein and MTT test the changes of SGC7901 cells proliferation in vitro and the sensitivity of chemotherapy drugs 5-Fu.Results:In 15 cases of gastric cancer tissue have the positive expression of 15 cases of SIRT1 protein,13 cases of P-gp protein and 3 cases of Top-Ⅱ alpha protein.In 15 cases of normal gastric mucosa tissues have the positive expression of 6 cases of SIRT1 protein,5 cases of P-gp protein and 0 cases of Top-Ⅱ alpha protein.The relative quantity of SIRT1 protein expression average were 0.385,0.827,0.009,0.232,0.275,0.159,0.275 in GES-1,SGC7901,MKN45,MKN28,HGC27,AGS and MGC803,respectively.The relative quantity of P-gp protein expression average were 0.339,0.526,1.03 in GES 1,SGC7901 and MKN45 and Top-Ⅱ alpha protein were 0.093,0.889,and 0.158,respectively,siRNA-SIRT1 transfected SGC7901 for 8 hours and after 72 hours to test the relative quantity of SIRT1 protein expression average were 0.965,0.937,0.958,0.567,0.253,0.083 in control,BC-V,negative,siRNA-1,2,3 SIRT1,P-gp were 1.893,1.905,1.932,0.465,0.006,0.465 and Top-Ⅱ alpha were 0.09,0.07,0.073,0.085,0.168,0.085.MTT results showed that after SIRT1 protein expression was inhibited the SGC7901 proliferation has no obvious change in vitro and cell sensitivity to the chemotherapy drugs 5-Fu was increased significantly.Conclusion:SIRT1 expression in gastric cancer tissues and the expression of SIRT1 in gastric cancer tissue and cell carcinoma factors role,SIRT1 protein overexpression can promote P-gp protein expression lower Top-Ⅱ alpha protein expression in gastric cancer cells to chemotherapy of multiple drug resistance increase.
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Chaihu Jia Longgu Muli Tang is a classical Chinese formulas treating Shaoyang syndrome complicated with Yangming syndrome according to Treatise on Febrile Diseases. This formula is used in mental disorder, nervous system, gynecologic, andrologic, and cardiovascular disease. However, its therapeutic effect on ischemia stroke and its mechanism is far from clear. In clinical practice, we have found that this formula is effective in treating ischemic stroke, which can shorten the course of the disease and reduce recurrence. The characteristics of this formula include: Shaoyang cardinal disadvantageous syndrome, mental and nervous symptoms, retained fluid punched upward syndrome and accumulation of heat in the stomach and intestines. By combining traditional Chinese medicine (TCM) pathogenesis and efficacy with modern pathology and pharmacology, we proposed that the TCM pathogenesis of stroke, which is characterized by hyperactivity of heat combining with phlegm, stasis and water drink, is consistent with syndromes and corresponding pathology targeted by Chaihu Jia Longgu Muli Tang, including the stress brain edema zone around the ischemic lesion, the increase of intracranial pressure, the excitement of sympathetic nerve, the release of monoamine neurotransmitter, the hypofunction of autonomic nervous system after stroke, and gastrointestinal stress response. Furthermore, the pharmacological mechanism of Chaihu Jia Longgu Muli Tang is concentrated on regulation the neuroendocrinology system centered by hypothalamic-pituitary-adrenal axis (HPA), participating in the process of neuron regeneration and apoptosis, oxidative stress, hyperactivity of sympathetic nerve, and inflammatory reaction. These pathological processes are consistent with the pathological changes after ischemic stroke. Therefore, Chaihu Jia Longgu Muli Tang is a key formula for treating ischemic stroke.
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Aim To further study the molecular mecha-nism of the herbs with hot nature on the regulational action on TRPV1 channel based on the 7900 Real-time PCR instrument. Methods 7900 PCR instrument was applied to detect the intracellular flurescence of TRPV1 channel in the dorsal root ganglions ( DRG ) neurons and the effect on the TRPV1 ’ s thermo-sensational functions of the selected 11 ingredients from hot herbs was explored. Results TRPV1 channels could be ac-tivated by gradually elevated temperature; the activa-tion process could be blocked by the TRPV1 specific blocking agent capsaizepine. Most of the ingredients from hot-nature herbs had the potential to up-regualate TRPV1 channel function. Conclusions The estab-lished TRPV1 channel detection system based on PCR instrument is suitable for the analysis of regulational functions of drugs on the heat-activated TRPV1 chan-nel;the functions of hot herbs may be related to the up-regualtional effects of its active ingredients on the TRPV1 channel which will further up-regulate energy metabolism.
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Aim The TRPV1 plasmid was transiently transfected into human embryonic kidney HEK 293T cells to establish the heterologous expression system of TRPV1-channel. Methods The transfection efficiency was confirmed under fluorescence mi-croscope and the TRPV1 protein expression was identified by u-sing Western blot, and the functional characteristics of the chan-nel were studied by using the method of confocal microscopy. Results The transfection rate could reach 40% ~50%; the transfected cells were found to have a clear band at the corre-sponding position that TRPV1 should be, which indicated that TRPV1 channel protein was expressed in the transfected cells. The confocal microscopy imaging result showed that the trans-fected HEK 293T cells were activated by TRPV1 channel ago-nist. Conclusion Transient transfection of HEK 293T cells with TRPV1 channel is successfully constructed and the heterol-ogous TRPV1 channel is verified to have normal calcium-media-ting function.
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Bitter taste receptors (BTRs) belong to the G protein-coupled receptors, which included 25 subtypes. BTRs, which were distributed in the oral cavity, mediated the bitter taste of mammalian. Furthermore, BTRs were also existed in the extra-oral digestive system such as the stomach and intestine to influence the digestion, absorption and energy regulation. It also can relax airway smooth muscles in the respiratory system and decrease blood pressure in the cardiovascular system. While being strikingly conformed to the latest advancements of BTRs, the efficacy of bitter taste property of Chinese materia medica (CMM) such as“excretion”,“dryness” and“strengthening” have been used in ancient theories of property and flavor in traditional Chinese medicine (TCM) for thousands of years in the treatment of multisystem diseases such as digestive, endocrine, respiratory and cardiovascular system. Therefore, applying modern techniques and new methods in the interpretation of the scientific connotation of bitter taste property of CMM based on BTRs should be a feasible way and a new research pattern. It played an important role in the enriching of the property theory in CMM, as well as enhancing the modernization and objectivization of CMM.
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To further uncover the scientific significance and molecular mechanism of the Chinese herbs with pungent hot or warm natures, endogenous and exogenous expression systems were established by isolation of dorsal root ganglion (DRG) neurons and transfection of HEK293 cells with TRPV1 channel gene separately. On this basis, the regulation action of capsaicin, one main ingredient from chili pepper, on TRPV1 channel was further explored by using confocal microscope. Besides, the three-sites one-unit technique and method were constructed based on the brown adipose tissue (BAT), anal and tail skin temperatures. Then the effect of capsaicin on mouse energy metabolism was evaluated. Both endogenous and exogenous TRPV1 channel could be activated and this action could be specifically blocked by the TRPV1 channel inhibitor capsazepine. Simultaneously, the mice's core body temperature and BAT temperature fall down and then go up, accompanied by the increase of temperature of the mice's tail skin. Promotion of the energy metabolism by activation of TRPV1 channel might be the common way for the pungent-hot (warm) herbs to demonstrate their natures.
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To further uncover the scientific significance and molecular mechanism of the Chinese herbs with pungent hot or warm natures, endogenous and exogenous expression systems were established by isolation of dorsal root ganglion (DRG) neurons and transfection of HEK293 cells with TRPV1 channel gene separately. On this basis, the regulation action of capsaicin, one main ingredient from chili pepper, on TRPV1 channel was further explored by using confocal microscope. Besides, the three-sites one-unit technique and method were constructed based on the brown adipose tissue (BAT), anal and tail skin temperatures. Then the effect of capsaicin on mouse energy metabolism was evaluated. Both endogenous and exogenous TRPV1 channel could be activated and this action could be specifically blocked by the TRPV1 channel inhibitor capsazepine. Simultaneously, the mice's core body temperature and BAT temperature fall down and then go up, accompanied by the increase of temperature of the mice's tail skin. Promotion of the energy metabolism by activation of TRPV1 channel might be the common way for the pungent-hot (warm) herbs to demonstrate their natures.
Subject(s)
Animals , Humans , Mice , Adipose Tissue, Brown , Physiology , Capsaicin , Pharmacology , Energy Metabolism , Ganglia, Spinal , Cell Biology , HEK293 Cells , Neurons , Physiology , Plants, Medicinal , Chemistry , TRPV Cation Channels , Physiology , Temperature , ThermogenesisABSTRACT
Siraitia grosvenorii is a perennial herb endemic to Guangxi province of China. Its fruit, commonly known as Luo hanguo, and has been used for hundreds of years as a natural sweetener and as a traditional medicine for the treatment of pharyngitis, pharyngeal pain, as well as an anti-tussive remedy in China. Based on ninety-three literary sources, this review summarized the advances in chemistry, biological effects, and toxicity research of S. grosvenorii during the past 30 years. Several different classes of compounds have been isolated or detected from various parts of S. grosvenorii, mainly triterpenoids, flavonoids, polysaccharides, amino acids, and essential oils. Various types of extracts or individual compounds derived from this species exhibited a wide array of biological effects e.g. anti-tussive, phlegm-relieving, anti-oxidant, immunomodulatory, liver-protecting, glucose-lowering, and anti-microbial. The existing research has shown that extracts and individual compounds from S. grosvenorii are basically non-toxic. Finally, some suggestions for further research on specific chemical and pharmacological properties of S. grosvenorii are proposed in this review.
Subject(s)
Animals , Humans , Amino Acids , Cucurbitaceae , Chemistry , Flavonoids , Plant Extracts , Pharmacology , Polysaccharides , TriterpenesABSTRACT
Objective To evaluate the renal protective effect of targeted abdominal perfusion pressure (APP) treatment in intra-abdominal hypertension (IAH) and further investigate its related mechanisms.Methods Twelve healthy pigs were randomly divided into experimental group and control group,each group had 6 pigs.All animals were collected urine volume each hour,continuously monitored mean arterial pressure (MAP) and renal cortical blood flow after anesthesia.IAH models were established by intraperitoneally injecting carbon dioxide in all animals,the baseline MAP,intra-abdominal pressure (IAP)and APP were obtained before IAH models established.In both groups,IAP was raised gradually from 0 mm Hg to 10 mm Hg,20 mm Hg and 30 mm Hg.In control group,IAP was maintained at 30 mm Hg for 8 hours with-out any other interventions.In experimental group,the animals were intravenously given with norepinephrine in order to get a target level of APP equal to its baseline values after 15 minutes of the onset of 30 mm Hg IAP.Changes of renal cortical blood flow,serum creatinine,TNF-α,IL-6 and urine IL-18 with the alteration of IAP in both groups were explored.Animals were then sacrificed for renal histopathology after 8 hours of the onset of 30 mm Hg IAP.Results With the increase of IAP,renal cortical blood flow in both groups was significantly decreased (P ＜ 0.01).Compared to its baseline,serum Cr and urinary IL-18 were significantly up-regulated after the maintenance of IAP at 30 mm Hg for 6 hours in both groups (P ＜ 0.05).However,in experimental group,which utilized a strategy of targeted APP,significant improvement of the renal cortical blood flow was observed (P ＜ 0.01),and urinary IL-18 was significantly lower than the control group (P ＜ 0.05).Renal histopathological examination found no obvious abnormalities either in control group or in experimental group.Conclusions The targeted APP treatment may have some renal protective function within the first 8 hours of IAH by improving renal cortical blood flow rather than affecting systemic inflammatory response.
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<p><b>OBJECTIVE</b>To explore the pathological mechanisms of Guizhi Decoction () syndrome and the therapeutic molecular mechanisms of the Guizhi Decoction, Mahuang Decoction (), Sangju Decoction ( ) and Yinqiao Powder (), as well as the potentially biological basis that Guizhi Decoction is most effective only for the patients with Guizhi Decoction syndrome in clinical practice.</p><p><b>METHODS</b>We first got serum samples from the patients suffering from both upper respiratory tract infection and Guizhi Decoction syndrome identified by the doctors of Chinese medicine (CM) in the clinic. Four formulas with therapeutic actions of pungent warmth or pungent coolness for superficial syndromes were chosen and four kinds of rat serum samples each containing one of the above-mentioned herbal formulas were collected, then the effects of Guizhi Decoction syndromes' patient serum as well as the effects of sera containing the formulas after being stimulated by the patient serum samples on both the mRNA expression of certain toll-like receptor (TLR) subtypes and the release of some inflammatory cytokines in RAW264.7 cells were tested and analyzed in vitro.</p><p><b>RESULTS</b>The expression of TLR-3, TLR-4 and TLR-9 mRNA among the 9 tested TLR subforms were up-regulated in the macrophages stimulated by the sera from untreated upper respiratory infection patients with the Guizhi Decoction syndrome (symptomcomplex). The products such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-β from stimulated macrophages through TLR signaling pathways were also increased correspondingly. Interestingly, the changes induced by the Guizhi Decoction syndrome patients' sera were masked significantly after the macrophages were incubated with the sera from donors treated with Guizhi Decoction. Similarly, the three other exterior-releasing formulas were all effective in reversing the up-regulated changes of certain TLR subforms to different degrees, but both the number of targeted TLRs and efficacy of them seemed to be inferior to that of Guizhi Decoction.</p><p><b>CONCLUSION</b>Evidence from these experiments might contribute to the scientific explanation of both the pharmacological mechanisms of Guizhi Decoction and also the CM theory that Guizhi Decoction is specifically prescribed for the treatment of Guizhi Decoction syndrome (The gearing formula to the symptom-complex).</p>
Subject(s)
Animals , Female , Humans , Male , Mice , Middle Aged , Rats , Cell Survival , Genetics , Cytokines , Bodily Secretions , Drugs, Chinese Herbal , Pharmacology , Gene Expression Regulation , Healthy Volunteers , Inflammation Mediators , Metabolism , Inhibitory Concentration 50 , Macrophages , Metabolism , RNA, Messenger , Genetics , Metabolism , Rats, Sprague-Dawley , Syndrome , Toll-Like Receptors , Genetics , MetabolismABSTRACT
Nowadays there are still a lot of controversies about indications methods and timing for tracheotomy in the patients who need long-term mechanical ventilation.Some recent studies have shown that early tracheostomy can increase patient comfort compliance and may reduce the use of sedatives,decrease ventilator associated pneumonia occurrence,reduce duration of mechanical ventilation and ICU stay.Presently we consider that the early tracheostomy may benefit patients needing long-term mechanical ventilation,and percutaneous dilational tracheostomy is a better way of tracheotomy,however we need to correctly grasp the indications.
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The theory of herbal properties of traditional Chinese medicine (TCM) is an indispensable part of theoretical system of TCM and plays an important role in the clinical prescription and application of TCM. In this theoretical system, the theory of four herbal properties takes a core and dominant position and becomes an indispensable part of TCM natures and actions. In combination of studies and experience, this essay proposes the latest discovery in modern biology-modern scientific connotation of cold and hot herbal properties on the basis of cold and hot perceptions of organism on the basis of analysis and summary of TRP channel protein and correlation of cold and hot perceptions of organism and thermoregulation, which is an effective approach to make breakthroughs in studies on modernization drive of the theory of four herbal properties of TCM.
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Animals , Humans , Body Temperature Regulation , Drug Therapy , Drugs, Chinese Herbal , Chemistry , Therapeutic Uses , Medicine, Chinese Traditional , Perception , Transient Receptor Potential Channels , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the occupational exposure levels of dust in new suspension preheated dry process (NSP) cement production line and put forward rectification measures for dust-exposed posts, and to provide ideas for the modern cement production enterprises in dust control and occupational health management.</p><p><b>METHODS</b>Occupational health field investigation combined with field test were used to measure the time-weighted average concentration (C(TWA)) of the dust in the workplace. Rectification measures were taken for the dust-exposed posts with unqualified dust concentration, and the protective effects of dustproof facilities in the rectified workplace were evaluated.</p><p><b>RESULTS</b>The field investigation revealed incompletely closed dustproof facilities, improperly set dust hoods, excess of dust leakage points, and other problems in the dust-exposed posts of an NSP cement production line before rectification, and the dustproof facilities could hardly exert dust removal effect. The field test showed that the vast majority of dust-exposed posts had the dust concentrations exceeding the occupational exposure limits (OELs), with a qualified rate as low as 31.8%. A series of rectification measures were taken for these posts. After the rectification, the dust-exposed posts demonstrated dramatically dropped C(TWA), and the qualified rate of dust concentration in the dust-exposed posts rose to 90.9%.</p><p><b>CONCLUSION</b>The dust hazards in NSP cement production line cannot be ignored. Taking appropriate protective measures are critical for curbing dust hazards in modern cement production.</p>
Subject(s)
Humans , Air Pollutants, Occupational , Construction Materials , Dust , Occupational Exposure , WorkplaceABSTRACT
Cinnamaldehyde was shown to have significant anti-inflammatory and anti-pyretic actions in studies from both others' and our lab. Prostaglandin E2 (PGE2) plays a key role in generation of these pathological states, while PGE, synthase-1 (mPGES-1) is one of crucial biological elements in the process of PGE2 production. And as a downstream inducible terminal prostaglandin synthase of COX-2, mPGES-1 is now regarded as a more promising novel drug target than COX-2 and is attracting more and more attention from both academia and pharmaceutical industry. The purpose of present study was to further investigate the anti-inflammatory and antipyretic molecular mechanisms of cinnamaldehyde based on the mouse macrophage cell line RAW264. 7 in vitro. The PGE2 was identified by using the method of enzyme-linked immunosorbent assay (ELISA) and the expression of COX-2 and mPGES-1 at mRNA and protein levels was detected by the Real-time PCR and Western blotting methods respectively. The experimental results suggested that cinnamaldehyde could evidently reverse the increased production of PGE2induced by IL-1beta. Moreover, the up-regulated expression levels of mPGES-1 and COX-2 were significatly decreased. Together, these results provide compelling evidence that the down-regulated actions to both the production of PGE2 as well as the expression of mPGES-I might account for, at least in part, the anti-inflammatory and anti-pyretic effects of cinnamaldehyde.
Subject(s)
Animals , Mice , Acrolein , Pharmacology , Blotting, Western , Cell Line , Dinoprostone , Metabolism , Interleukin-1beta , Pharmacology , Intramolecular Oxidoreductases , Metabolism , Macrophages , Metabolism , Prostaglandin-E Synthases , Real-Time Polymerase Chain ReactionABSTRACT
<p><b>BACKGROUND</b>Tracheostomy should be considered to replace endotracheal intubation in patients requiring prolonged mechanical ventilation (MV). However, the optimal timing for tracheostomy is still a topic of debate. The present study aimed to investigate whether early percutaneous dilational tracheostomy (PDT) can reduce duration of MV, and to further verify whether early PDT can reduce sedative use, shorten intensive care unit (ICU) stay, decrease the incidence of ventilator associated pneumonia (VAP), and increase successful weaning and ICU discharge rate.</p><p><b>METHODS</b>A prospective, randomized controlled trial was carried out in a surgical ICU from July 2008 to June 2011 in adult patients anticipated requiring prolonged MV via endotracheal intubation. Patients meeting the inclusion criteria were randomly assigned to the early PDT group or the late PDT group on day 3 of MV. The patients in the early PDT group were tracheostomized with PDT on day 3 of MV. The patients in the late PDT group were tracheostomized with PDT on day 15 of MV if they still needed MV. The primary endpoint was ventilator-free days at day 28 after randomization. The secondary endpoints were sedation-free days, ICU-free days, successful weaning and ICU discharge rate, and incidence of VAP at day 28 after randomization. The cumulative 60-day incidence of death after randomization was also analyzed.</p><p><b>RESULTS</b>Total 119 patients were randomized to either the early PDT group (n = 58) or the late PDT group (n = 61). The ventilator-free days was significantly increased in the early PDT group than in the late PDT group ((9.57 ± 5.64) vs. (7.38 ± 6.17) days, P < 0.05). The sedation-free days and ICU-free days were also significantly increased in the early PDT group than in the late PDT group (20.84 ± 2.35 vs. 17.05 ± 2.30 days, P < 0.05; and 8.0 (interquartile range (IQR): 5.0 - 12.0) vs. 3.0 (IQR: 0 - 12.0) days, P < 0.001 respectively). The successful weaning and ICU discharge rate was significantly higher in early PDT group than in late PDT group (74.1% vs. 55.7%, P < 0.05; and 67.2% vs. 47.5%, P < 0.05 respectively). VAP was observed in 17 patients (29.3%) in early PDT group and in 30 patients (49.2%) in late PDT group (P < 0.05). There was no significant difference between the two groups in the cumulative 60-day incidence of death after randomization (P = 0.949).</p><p><b>CONCLUSIONS</b>The early PDT resulted in more ventilator-free, sedation-free, and ICU-free days, higher successful weaning and ICU discharge rate, and lower incidence of VAP, but did not change the cumulative 60-day incidence of death in the patients' anticipated requiring prolonged mechanical ventilation.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Critical Illness , Respiration, Artificial , Time Factors , Tracheostomy , MethodsABSTRACT
<p><b>OBJECTIVE</b>Wuji pill is a prescription of traditional Chinese medicine(TCM) and was composed of Rhizoma Coptidis, Fructus Evodiae Rutaecarpae and Radix Paeoniae Alba. The aim of this research is to investigate the effects of Wuji pill compound with different compatibility on the levels of enzymic activity of cytochrome P450 CYP3A1/3A2 in rat liver microsomes in vitro, and to confirm the compatibility mechanism of Wuji pill from the point of relationships between compound prescription of TCM and metabolism.</p><p><b>METHOD</b>With testosterone being a probe, the levels of enzymic activity of CYP3A1/3A2 were detected by HPLC, which were suppressed by Wuji pill with different compatibility in vitro.</p><p><b>RESULT</b>The IC50 of Rhizoma Coptidis, Fructus Evodiae Rutaecarpae, Radix Paeoniae Alba and 1"-9" of different level Wuji pill is: 38.96, 871.96, 15 519.17, 43.17, 60. 47, 276.12, 133.40, 118.08, 88. 47, 64. 36, 35. 13 and 39. 91 mg x L -', respectively. Rhizoma Coptidis and 1-9" of Wuji pill can suppress the enzymic activity of CYP3A1/3A2 significantly, and the capability of Rhizoma Coptidis in Wuji pill of action on CYP3A1/3A2 can be modified by different composition of Fructus Evodiae Rutaecarpae and Radix Paeoniae in Wuji pill, and there are statistical differences among the IC50 of 1#-9# of Wuji pill. While the ratio of Rhizoma Coptidis raises up in Wuji pill, Wuji pill may suppress the enzymic activity of CYP1A2 largely.</p><p><b>CONCLUSION</b>The reason why Wuji pill with different compatibility has different pharmacodynamics and pharmacokinetics characteristics is likely to lie in the difference of the capability of Wuji pill with different compatibility on CYP3A1/3A2. [Key words] Wuji pill; CYP3A1/3A2; testosterone; HPLC; different compatibility prescription of traditional Chinese medi-cine</p>