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OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).
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Diabetes Mellitus , Neuropatias Diabéticas , Plantas Medicinais , Humanos , Neuropatias Diabéticas/tratamento farmacológico , Banhos , Método Duplo-Cego , Extratos Vegetais/uso terapêuticoRESUMO
Ferroptosis is an iron-dependent cell death and is associated with cancer therapy. Can it play a role in resistance of postoperative infection of implants, especially with an extracellular supplement of Fe ions in a non-cytotoxic dose? To answer this, "nanoswords" of Fe-doped titanite are fabricated on a Ti implant surface to resist bacterial invasion by a synergistic action of ferroptosis-like bacteria killing, proton disturbance, and physical puncture. The related antibiosis mechanism is explored by atomic force microscopy and genome sequencing. The nanoswords induce an increased local pH value, which not only weakens the proton motive force, reducing adenosine triphosphate synthesis of Staphylococcus aureus, but also decreases the membrane modulus, making the nanoswords distort and even puncture a bacterial membrane easily. Simultaneously, more Fe ions are taken by bacteria due to increased bacterial membrane permeability, resulting in ferroptosis-like death of bacteria, and this is demonstrated by intracellular iron enrichment, lipid peroxidation, and glutathione depletion. Interestingly, a microenvironment constructed by these nanoswords improves osteoblast behavior in vitro and bone regeneration in vivo. Overall, the nanoswords can induce ferroptosis-like bacterial death without cytotoxicity and have great promise in applications with clinical implants for outstanding antibiosis and biointegration performance.
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Ferroptose , Osseointegração , Antibiose , Ferro/metabolismo , Staphylococcus aureus/metabolismo , ÍonsRESUMO
Accumulating evidence suggests that ginger and its pungent constituents harbor a wealth of biological activities including cancer chemopreventive activity. However, relatively few researches focus on [6]-dehydroshogaol (6-DHS) compared with other ginger pungent constituents such as [6]-shogaol (6S). In this work, we selected three ginger compounds, 6-DHS, 6S and [6]-paradol (6P) differentiated by the presence and number of the Michael acceptor units, to probe structural basis and mechanism of 6-DHS in inhibiting angiogenesis, a key step for tumor growth and metastasis. It was found that their antiangiogenic activity is significantly dependent on the presence and number of Michael acceptor units. Benefiting from its two Michael acceptor units, 6-DHS is the most potent inhibitor of thioredoxin reductase and depletor of glutathione, thereby being the most active generator of reactive oxygen species, which is responsible for its strongest ability to inhibit angiogenesis. This work highlights 6-DHS being a Michael acceptor-dependent pro-oxidative angiogenesis inhibitor.
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Zingiber officinale , Catecóis/farmacologia , Zingiber officinale/química , Zingiber officinale/metabolismo , Glutationa/metabolismo , Estresse Oxidativo , Extratos Vegetais/farmacologia , Tiorredoxina Dissulfeto RedutaseRESUMO
OBJECTIVE: To study the effect of intervening in the signal transduction pathways of TGF-ß1, Smad4 and Smad7 with Qianliexiao Decoction (QLX) on the proliferation and apoptosis of prostate fibroblasts (PrF) in mice with experimental autoimmune prostatitis (EAP). METHODS: A model of EAP with damp-heat syndrome was established in C57BL/6 mice by immunization induction combined with the TCM modeling method. The prostate tissue of the mice was harvested for isolation, culturing and purification of PrFs and detection of their purity. After modeling by stimulation with a medium containing >90%-purity or 5 ng/ml TGF-ß1, the PrFs in the logarithmic growth phase were obtained and randomly divided into a blank control (serum-free medium), a model control, a positive control (medium containing 5 ng/ml TGF-ß1), a low-dose QLX (serum containing 5% QLX), a medium-dose QLX (serum containing 10% QLX), and a high-dose QLX group (serum containing 20% QLX). After 24 hours of intervention, the proliferation of the PrFs was measured, the protein expressions of TGF-ß1, Smad4, Smad7, p-Smad4 and p-Smad7 detected by Western blot, their mRNA expressions determined by qPCR, and the apoptosis of the PrFs examined by flow cytometry. RESULTS: After induction with TGF-ß1, the proliferation of the PrFs was significantly increased in the positive control (P < 0.05), but inhibited in the medium- and low-dose QLX groups (P < 0.05) and even more significantly in the high-dose QLX group as compared with that in the model control (P < 0.01). The expressions of Smad4, p-Samd7 and TGF-ß1 proteins in the PrFs were remarkably higher in the positive control than in the model control group (P < 0.05), while those of p-Smad4 and TGF-ß1 markedly lower (P < 0.01) and that of p-Smad7 dramatically higher in the QLX intervention groups than in the positive control (P < 0.01), in an evident dose-dependent manner. In comparison with the model control group, the high-dose QLX group exhibited a significant decrease in the mRNA expression of Smad4 (P < 0.05) but all the three QLX groups showed a dramatic increase in those of Smad7 (P < 0.05) and TGF-ß1 (P < 0.01). The mRNA expression of Smad4 was markedly down-regulated in the high-dose QLX group compared with that in the positive control (P < 0.05), that of Smad7 up-regulated in the model control and QLX groups (P < 0.01), and that of TGF-ß1 down-regulated in the three QLX groups (P < 0.01). The apoptosis rate of the PrFs was significantly higher in the QLX groups than in the model control (P < 0.05) in a dose-dependent manner, but showed no statistically significant difference between the model control and the positive control groups (P > 0.05). CONCLUSIONS: TGF-ß1 can stimulate the proliferation of PrFs, up-regulate the expressions of TGF-ß1 and p-Smad4, and down-regulate that of p-Smad7, while QLX can inhibit the proliferation of PrFs in a dose-dependent manner by decreasing the expressions of TGF-ß1 and p-Smad4, increasing that of p-Smad7, and thereby suppressing TGF-ß1-induced proliferation of PrFs.
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Doenças Autoimunes/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Fibroblastos/efeitos dos fármacos , Prostatite/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fibroblastos/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína Smad4/metabolismo , Proteína Smad7/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
This study is aimed at identifying the effects of dietary fiber on gut health, as well as the association between that understanding and fiber consumption in fish. A total of 300 juvenile largemouth bass (micropterus salmoides, initial average weight: 15.38 ± 0.16g) were randomly divided into three treatment groups (4 replicates per group). Fish were fed with isoproteic and isolipidic diets containing 0% (low fiber, LF), 4% (moderate fiber, MF) and 8% (high fiber, HF) soybean fiber, respectively. The intestine and intestinal content of test fish per treatment group after 56 days of treatment were sampled. The results showed that the anterior intestinal sections had normal histological architecture, and no considerable damage or inflammation was observed in any histological section from all subjects examined. Curiously, fish fed the MF diet had better histological alterations than the other treatments. Meanwhile, the intestinal antioxidant capacity in the MF group was significantly promoted when compared to the other groups, as well as up-regulated expression of antioxidant-related genes including sod, cat and gpx with increasing dietary fiber concentrations. Importantly, the administrations of MF diet remarkably elevated largemouth bass innate immune parameters include intestinal inducible nitric oxide synthase (iNOS) activity, nitric oxide (NO) and total protein content. Similarly, dietary administrations of fiber down-regulated notablely the expression of pro-inflammatory cytokines including IL-8, IL-1ß and TNFα, whereas up-regulated tolerogenic cytokine IL-10 and TGF-ß1 mRNA levels. In addition, dietary fibers also modulated the community structure of the intestinal microbiota by significantly altering bacterial diversity. Dietary supplemental fibers regulated intestinal microbiota in largemouth bass, characterized by a reduced abundance of Fusobacteria along with increased abundances of Proteobacteria and Firmicutes. Taken together, the present results suggested that moderate fiber supplementation was beneficial to promoting intestinal health status of fish through antioxidant and anti-inflammatory effects, which could be at least partially responsible by the modulation of gut microbial composition.
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Bass/imunologia , Fibras na Dieta/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Ração Animal/análise , Animais , Dieta/veterinária , Fibras na Dieta/administração & dosagem , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Intestinos/anatomia & histologia , Intestinos/microbiologia , Distribuição Aleatória , Glycine max/químicaRESUMO
BACKGROUND: As a common complication of diabetes, the incidence of diabetic peripheral neuropathy (DPN) is 60-70% worldwide. DPN is a major risk factor for diabetic foot, which may lead to foot ulceration and even amputation. The treatment of DPN remains challenging. Our preliminary study demonstrated that the external application of Tangbi Waixi (TW) decoction to the lower extremities relieved clinical symptoms and improved nerve conduction velocity in DPN patients. The aim of this study was to verify the efficacy of TW among DPN patients and evaluate the herb mixture's safety using rigorous methodological designs. METHODS/DESIGN: This study is a multicenter, double-blind, randomized controlled trial. A total of 640 DPN patients will be recruited and randomized to receive a foot bath with either the TW decoction or control drug. Participants will be assessed at baseline and 12 and 24 weeks after treatment. The primary outcome was the change of the Toronto Clinical Scoring System (TCSS). Secondary outcomes were nerve conduction velocity, blood glucose, blood lipids, serum inflammatory cytokines, and the European Quality of Life Five-Dimension Scale (EQ-5D) and TCM symptom scores. DISCUSSION: This multicenter, prospective, randomized clinical trial will provide valuable data regarding the efficacy and safety of foot bath treatment with TW decoction. Positive results would provide a novel treatment regimen for DPN patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IOR-16009331 . Registered on 8 October 2016.
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Banhos/métodos , Pé Diabético/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Adolescente , Adulto , Idoso , Banhos/efeitos adversos , China , Pé Diabético/diagnóstico , Pé Diabético/fisiopatologia , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: This study aimed to determine whether resveratrol treatment alleviates endoplasmic reticulum stress and changes the expression of adipokines in adipose tissues and cells. METHODS: 8-week-old male C57BL/6 mice were fed a high-calorie diet (HCD group) or high-calorie diet supplemented with resveratrol (high-calorie diet + resveratrol group) for 3 months. Insulin resistance, serum lipids and proinflammatory indices, the size and inflammatory cell infiltration in subcutaneous and visceral adipose tissues were analyzed. The gene expressions of endoplasmic reticulum stress, adipokines, and inflammatory cytokines were determined. The induced mature 3T3-L1 cells were pretreated with resveratrol and then palmitic acid, and the gene expressions of endoplasmic reticulum stress, adipokines, and inflammatory cytokines were determined. RESULTS: Subcutaneous and visceral adipose tissues in the high-calorie diet-fed mice exhibited adipocyte hypertrophy, inflammatory activation, and endoplasmic reticulum stress. Resveratrol alleviated high-calorie diet-induced insulin resistance and endoplasmic reticulum stress, increased expression of SIRT1, and reversed expression of adipokines in varying degrees in both subcutaneous and visceral adipose tissues. The effects of resveratrol on palmitic acid-treated adipocytes were similar to those shown in the tissues. CONCLUSIONS: Resveratrol treatment obviously reversed adipocyte hypertrophy and insulin resistance by attenuating endoplasmic reticulum stress and inflammation, thus increasing the expression of SIRT1 and inverting the expression of adipokines in vivo and in vitro.
Assuntos
Adipócitos/efeitos dos fármacos , Adipocinas/metabolismo , Tecido Adiposo/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Ácido Palmítico/farmacologia , Estilbenos/farmacologia , Células 3T3-L1 , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Resistência à Insulina/fisiologia , Lipídeos/sangue , Masculino , Camundongos , ResveratrolRESUMO
OBJECTIVE: To investigate the effect of waist hot-compress with the Shirexiao (SRX) pad on the expressions of Th17/Treg-specific factors in the prostatic tissue of the mouse model of experimental autoimmune prostatitis (EAP) with damp heat syndrome, and explore its possible action mechanisms. METHODS: Twenty healthy male mice were included as normal controls and another 100 chosen for establishing the model of EAP with damp heat syndrome by subcutaneous injection of purified prostate protein solution from the Wistar rat and Freund's complete adjuvant using the TCM method. The model mice were randomly divided into five groups: model control, matrix, and low-, medium- and high-dose SRX. After chemical removal of the hair at lumbar vertebrae 1ï¼3, the animals of the low-, medium- and high-dose SRX groups were treated with the SRX pad heated to 45â and externally applied to the non-hair area, qd, bid, and tid, respectively, 10 minutes each time, those of the matrix group with the vaseline pad, and those of the normal and model control groups with the saline pad. After 4 weeks of continuous treatment, all the mice were sacrificed for determination of the protein and mRNA expressions of RORγt and Foxp3 in the prostate tissue by Western blot and quantitative real-time PCR. RESULTS: The symptoms, signs and pathological changes of the EAP model mice were similar to the manifestations of chronic prostatitis. After intervention, the protein and mRNA expressions of Foxp3 were significantly down-regulated while those of RORγt markedly up-regulated in the EAP model group as compared with the normal control (P <0.05). In comparison with the model controls, the protein and mRNA expressions of RORγt were remarkably decreased in the medium- and high-dose SRX groups (P <0.05), that of the Foxp3 protein was markedly increased in the high-dose group (P <0.05), while that of Foxp3 mRNA exhibited no statistically significant difference in the low-, medium- or high-dose groups (P >0.05). CONCLUSIONS: The Shirexiao waist hot-compress therapy plays a positive role in the treatment of autoimmune prostatitis with damp heat syndrome by reducing the expression of RORγt, inhibiting the differentiation of Th17 and thus checking the differentiation imbalance of Th17/Treg.
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Bandagens Compressivas , Temperatura Alta , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Prostatite/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Adjuvantes Imunológicos , Animais , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Fatores de Transcrição Forkhead/metabolismo , Adjuvante de Freund , Remoção de Cabelo , Humanos , Masculino , Camundongos , Prostatite/etiologia , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Regulação para CimaRESUMO
As a typical representative of Lepidopteran insects, the silkworm, Bombyx mori, has numerous advantages, such as simple husbandry,highly prolific nature, short generation time, easily handled to be operated with moderate body size, clear genetic background and abundant mutation resources. Silkworm has not only been studied by the geneticists, but also been used as a new laboratory animal model of human disease and drug screening. There is a plenty of genetic resources in silkworm, some of which could be used as models of human genetic diseases, such as Phenylketonuria, Parkinson's disease, Hermansky-Pudlak syndrome and so on. Silkworm has also played a significant role in the study of pathogenesis of human pathogenic microorganisms. Moreover, silkworm could be used to evaluate the pharmacokinetic/pharmacodynamics properties and safety of a new drug comprehensively and systematically. At the same time, it can be used in the high throughput drug screening assays to shorten the period of the new drug research and development. This review summarizes that the silkworm is an excellent model in the drug screening assays, and has a potential in application to the large-scale drug screening.
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Bombyx , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Animais , HumanosRESUMO
OBJECTIVE: To explore the effect and specific mechanism of lung-tonifying and expectorant decoction on lung cancer rats with Qi deficiency and blood stasis, and aim to provide a new idea on treating the disease with traditional Chinese medicine based on syndrome differentiation. METHODS: A total of 60 C57BL/6J male rats were included in the study. The model of Qi deficiency and blood stasis was established in 60 rats by using multiple-factor stimulation. About 10 rats were randomly taken to verify whether the model establishment was successful and the rest of 50 rats were divided into 5 groups with 10 rats each: blank control group, cisplatin group, low dose group, medium dose group and high dose group. The blank control group was treated with normal saline, and cisplatin group was treated with cisplatin while the other three groups were treated with lung-tonifying and expectorant decoction at different doses. The volume change in transplanted tumor, tumor inhibition rate, apoptosis rate, and expression of Bcl-2, Bax, cleaved caspase-3 and cleaved caspase-9 in 5 groups were compared. RESULTS: The rapidest growth rate of transplanted tumor volume was observed in blank control group and the slowest in cisplatin group. The growth rate was gradually decreased with the increasing dose of lung-tonifying and expectorant decoction, and the difference in growth of tumor volume among groups was statistically significant (P < 0.05). The cisplatin group showed the highest tumor inhibition rate, with dose-dependent increase (P < 0.05). The apoptosis rate in low dose group was higher than blank control group but lower than high dose group (P < 0.05). The apoptosis rate in medium dose group was significantly higher than blank control group (P < 0.05). The apoptosis rate in high dose group was significantly higher than control group (P < 0.05). The positive expression rates of Bcl-2 and Bax in all groups showed statistically significant difference (P < 0.05), while expression of cleaved caspase-3 and cleaved caspase-9 in 5 groups was significantly different, with dose-dependent increase (P < 0.05). CONCLUSIONS: The lung-tonifying and expectorant decoction inhibits the proliferation of tumor cells by inducing and activating the cell apoptosis in treatment of lung cancer with Qi deficiency and blood stasis, probably with good clinical therapeutic effect.
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OBJECTIVE: Photodynamic therapy (PDT) triggers various cellular responses and induces cell death via necrosis and/or apoptosis. This study evaluated the feasibility of using O2 and Ca(2+) fluxes as indicators of apoptosis induced by rose bengal (RB)-mediated PDT in human oral squamous carcinoma cells (Cal27 cells). METHODS: Intracellular reactive oxygen species (ROS) generation was assessed by the dichloro-dihydro-fluorescein diacetate (DCFH-DA) method. Real-time O2 and Ca(2+) flux measurements were performed using the noninvasive micro-test technique (NMT). Apoptosis of the PDT-treated cells was confirmed by 4'6-diamidino-2-phenylindole-dilactate staining. The activation of apoptosis-related molecules was examined using Western blot. We assayed the effects of the fluctuation of O2 and Ca(2+) flux in response to PDT and the apoptotic mechanism, by which ROS, O2, and Ca(2+) synergistically may trigger apoptosis in PDT-treated cells. RESULTS: Real-time O2 and Ca(2+) flux measurements revealed that these indicators were involved in the timely regulation of apoptosis in the PDT-treated cells and were activated 2 h after PDT treatment. RB-mediated PDT significantly elicited the generation of ROS by approximately threefold, which was critical for PDT-induced apoptosis. Cytochrome c and cleaved caspase-3, caspase-9 and poly ADP ribose polymerase (PARP) were overexpressed, and the data provided evidence that 2 h was considered to be the key observation time in RB-mediated PDT-induced apoptosis in Cal27 cells. CONCLUSIONS: Our collective results indicated that the effects of O2 and Ca(2+) fluxes may act as a real-time biomonitoring system of apoptosis in the RB-PDT-treated cells. Also, RB-mediated PDT can be a potential and effective therapeutic modality in oral squamous cell carcinoma.
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Apoptose/efeitos da radiação , Carcinoma de Células Escamosas/metabolismo , Corantes Fluorescentes/farmacologia , Neoplasias Bucais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Rosa Bengala/farmacologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/radioterapiaRESUMO
[6]-Gingerol and [6]-shogaol are the major pungent components in ginger with a variety of biological activities including antioxidant activity. To explore their structure determinants for antioxidant activity, we synthesized eight compounds differentiated by their side chains which are characteristic of the C1-C2 double bond, the C4-C5 double bond or the 5-OH, and the six- or twelve-carbon unbranched alkyl chain. Our results show that their antioxidant activity depends significantly on the side chain structure, the reaction mediums and substrates. Noticeably, existence of the 5-OH decreases their formal hydrogen-transfer and electron-donating abilities, but increases their DNA damage- and lipid peroxidation-protecting abilities. Additionally, despite significantly reducing their DNA strand breakage-inhibiting activity, extension of the chain length from six to twelve carbons enhances their anti-haemolysis activity.
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Antioxidantes/química , Catecóis/química , Álcoois Graxos/química , Extratos Vegetais/química , Dano ao DNA , Peroxidação de LipídeosRESUMO
OBJECTIVE: To study chemical constituents from petroleum ether-soluble parts of cones of Platycladus orientalis. METHODS: The compound were isolaeed by repeated column chromatography of silica gel and Sephadex LH-20. The structures were elucidated by physicochemical properties and spectrum analysis. RESULTS: Seven constituents were isolated and identified as sandaracopimaric acid (1), 6alpha-hydroxy sandaracopimaric acid (2), ent-isopimara-8 (14), 15-dien-3beta, 19-diol (3), ent-isopimara-8 (9), 15-dien-3beta-ol (4), ent-isopimara-8 (14),15- dien-3beta-ol (5), isocupressic acid (6) and 15-acetylisocupressic acid (7). CONCLUSION: Compounds 2 and 7 are isolated from this genus for the first time.
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Cupressaceae/química , Diterpenos/química , Medicamentos de Ervas Chinesas/química , Frutas/química , Alcanos/química , Ácidos Carboxílicos/química , Ácidos Carboxílicos/isolamento & purificação , Diterpenos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Tetra-Hidronaftalenos/química , Tetra-Hidronaftalenos/isolamento & purificaçãoRESUMO
Based on the observed biological activities of coumarins and resveratrol, we synthesized fourteen hydroxylated 3-phenylcoumarins (stilbene-coumarin hybrids) including six novel ortho-hydroxy-methoxy substituted derivatives, 1-14, by Perkin reaction. We characterized these compounds concerning their antioxidant activity against 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced pBR322 DNA strand breakage, and their antiproliferative effects on human promyelocytic leukemia HL-60 and human lung adenocarcinoma epithelial A549 cells. Structure-activity relationship information suggests that the introduction of ortho-hydroxy-methoxy groups and ortho-dihydroxy groups on the aromatic A ring could efficiently improve antiproliferative activity. Interestingly, a new derivative, 6-methoxy-7-hydroxy-3-(4'-hydroxyphenyl)coumarin, 9, behaved as a poor antioxidant but appeared to be the most potent antiproliferative agent among the compounds examined, and this activity was mediated by deregulation in cell cycle and induction of apoptosis.
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Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antioxidantes/síntese química , Antioxidantes/farmacologia , Cumarínicos/síntese química , Cumarínicos/farmacologia , Adenocarcinoma/patologia , Antineoplásicos/química , Antioxidantes/química , Linhagem Celular Tumoral , Cumarínicos/química , Dano ao DNA , Avaliação Pré-Clínica de Medicamentos , Humanos , Neoplasias Pulmonares/patologia , Relação Estrutura-AtividadeRESUMO
Based on the bottom trawl survey data in May 2007 and May and June 2008, this paper analyzed the effects of the abundance dynamics of macro-jellyfish on the species composition, distribution, and abundance of fishery resource in the Yangtze River estuary and its adjacent waters. From May 2007 to June 2008, the average catch per haul and the top catch per haul of macro-jellyfish increased, up to 222.2 kg x h(-1) and 1800 kg x h(-1) in June 2008, respectively. The macro-jellyfish were mainly distributed in the areas around 50 m isobath, and not beyond 100 m isobath where was the joint front of the coastal waters of East China Sea, Yangtze River runoff, and Taiwan Warm Current. The main distribution area of macro-jellyfish in June migrated northward, as compared with that in May, and the highest catches of macro-jellyfish in May 2007 and May 2008 were found in the same sampling station (122.5 degrees E, 28.5 degrees N). In the sampling stations with higher abundance of macro-jellyfish, the fishery abundance was low, and the fishery species also changed greatly, mainly composed by small-sized species (Trachurus japonicus, Harpadon nehereus, and Acropoma japonicum) and pelagic species (Psenopsis anomala, Octopus variabilis) and Trichiurus japonicus, and P. anomala accounted for 23.7% of the total catch in June 2008. Larimichthys polyactis also occupied higher proportion of the total catch in sampling stations with higher macro-jellyfish abundance, but the demersal species Lophius litulon was not found, and a few crustaceans were collected. This study showed that macro-jellyfish had definite negative effects on the fishery community structure and abundance in the Yangtze River estuary fishery ecosystem, and further, changed the energy flow patterns of the ecosystem through cascading trophic interactions. Therefore, macro-jellyfish was strongly suggested to be an independent ecological group when the corresponding fishery management measures were considered.
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Ecossistema , Pesqueiros , Cifozoários/crescimento & desenvolvimento , Animais , China , Oceanos e Mares , Dinâmica Populacional , RiosRESUMO
Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, 1) is a yellow ingredient isolated from turmeric (curcumin longa). Many health benefits have been claimed for curcumin, and these have generally been ascribed to its radical-trapping antioxidant properties. In order to find more active antioxidants with 1 as the lead compound, we synthesized curcumin analogues, i.e., 1,7-bis(3,4-dihydroxyphenyl)-1,6-heptadiene-3,5-dione (2), 1-(3,4-dihydroxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (3), 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (4), 1,7-bis (4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (5), 1,7-bis(3,4-dimethoxyphenyl)-1,6-heptadiene-3,5-dione (6), 1,7-bis(4-methoxyphenyl)-1,6-heptadiene-3,5-dione (7), and 1,7-diphenyl-1,6-heptadiene-3,5-dione (8). Antioxidative effects of curcumin and these analogues against the peroxidation of linoleic acid were studied in sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB) micelles. The peroxidation was initiated thermally by a water-soluble initiator 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), and reaction kinetics were monitored by the formation of linoleic acid hydroperoxides. Kinetic analysis of the antioxidation process demonstrates that these compounds, except 6, 7 and 8, are effective antioxidants in micelles by H-atom abstraction from the phenolic groups. Compounds 2 and 3, which bear ortho-diphenoxyl functionality, possess significantly higher antioxidant activity than curcumin and other analogues, and the 4-hydroxy-3-methoxyphenyl group also plays an important role in the antioxidative activity. In addition, the synergistic antioxidant effect of these compounds with alpha-tocopherol (vitamin E) in micelles was also studied by following the formation of linoleic acid hydroperoxides and the consumption of alpha-tocopherol. It was found that these compounds could not synergistically interact with alpha-tocopherol in micelles.
Assuntos
Antioxidantes/química , Curcumina/análogos & derivados , Curcumina/química , Ácidos Linoleicos/química , Peroxidação de Lipídeos , Peróxidos Lipídicos/química , Radicais Livres/química , Micelas , Estrutura Molecular , alfa-Tocoferol/químicaRESUMO
The synergistic antioxidant effect of polyphenols extracted from green tea, i.e. (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin gallate (EGCG) and gallic acid (GA), with alpha-tocopherol (vitamin E) and L-ascorbic acid (vitamin C) against the peroxidation of linoleic acid has been studied in sodium dodecyl sulfate (SDS) micelles. The peroxidation was initiated thermally by a water-soluble azo initiator 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH), and the reaction kinetics were studied by monitoring the formation of linoleic acid hydroperoxides and consumption of the antioxidants. It was found that the mixture of the green tea polyphenol, vitamin E and vitamin C could act synergistically to protect lipid peroxidation. Kinetic and mechanistic studies on the antioxidation process revealed that this antioxidant synergism was due to the regeneration of vitamin E by the green tea polyphenol and the regeneration of the latter by vitamin C.
Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Flavonoides/farmacologia , Micelas , Fenóis/farmacologia , Dodecilsulfato de Sódio , Chá/química , alfa-Tocoferol/farmacologia , Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Catequina/análogos & derivados , Catequina/metabolismo , Misturas Complexas/metabolismo , Misturas Complexas/farmacologia , Flavonoides/metabolismo , Radicais Livres/farmacologia , Meia-Vida , Cinética , Ácido Linoleico/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fenóis/metabolismo , Polifenóis , alfa-Tocoferol/metabolismoRESUMO
Three kinds of adsorbents-potassium dihydrogen phosphate, sawdust and mixture of potassium dihydrogen phosphate and sawdust were added respectively into composting to investigate their adsorption effect on ammonia. The experimental results showed that all the adsorbents could restrain ammonia volatilizing, with the sorption of potassium dihydrogen phosphate adsorbents being the best of all, the sorption of mixture adsorbent with potassium dihydrogen phosphate and sawdust being the second and the sorption of sawdust adsorbent being the last. Therefore, the total nitrogen loss ratios respectively reduced from 38% to 13%, 15% and 21% after adding these three kinds of adsorbents into composting. However, potassium dihydrogen phosphate produced negative influence on composting properties as its supplemented amount exceeded a quantity basis equivalent to 18% of total nitrogen in the composting, for example: pH value had been lessened, microorganism activity reduced, which finally resulted in the reduction of biodegradation ratio of organic matter. But it did not result in these problems when using the mixture of potassium dihydrogen phosphate and sawdust as adsorbent, in which the amount of potassium dihydrogen phosphate was under a quantity basis equivalent to 6% of total nitrogen in the composting. Moreover, the mixture adsorbent produced better adsorption effect on ammonia, and raised biodegradation ratio of organic matter from 26% to 33%.
Assuntos
Amônia/química , Poeira , Fosfatos/química , Compostos de Potássio/química , Eliminação de Resíduos/métodos , Solo , Adsorção , Aerobiose , Reatores Biológicos , Nitrogênio/química , Nitrogênio/metabolismo , MadeiraRESUMO
BACKGROUND AND AIM: Intestinal microflora play a crucial role in some severe liver diseases. The purpose of this study was to evaluate the effects of a Lactobacillus strain and a Bifidobacterium strain on ischemia-reperfusion (I/R) liver injury. METHODS: Rats were divided into six groups. Each group received either Bifidobacterium Catenulatum ZYB0401; Lactobacillus Fermentum ZYL0401; a mixture of these two bacterial strains; gentamicin; or saline by daily gavage for 7 days. On the sixth day, all rats, except those in the control group, were subjected to 20 min of liver ischemia. After 22 h of hepatic reperfusion, liver enzymes and histology, malondialdehyde (MDA), superoxide dismutase (SOD), endotoxemia, serum tumor necrosis factor-alpha (TNF-alpha), intestinal bacteria, intestinal mucosal ultrastructure, and bacterial translocation were studied. RESULTS: All administered bacteria increased intestinal Bifidobacterium and Lactobacillus, decreased endotoxemia (P < 0.01), alanine aminotransferase (ALT) (P < 0.01), and markedly ameliorated liver histology and intestinal mucosal ultrastructure. Only rats treated with Bifidobacterium Catenulatum ZYB0401 and Lactobacillus Fermentum ZYL0401 showed reduced incidence of bacterial translocation to the kidney (P < 0.05), associated with decreased serum TNF-alpha and liver MDA (P < 0.05) and increased liver SOD (P < 0.05) compared to the I/R group. Gentamicin decreased almost all kinds of intestinal bacteria (P < 0.01) and decreased ALT (P < 0.01) and serum TNF-alpha, but failed to reduce both endotoxemia and the incidence of bacterial translocation and had no effects on liver MDA and SOD. CONCLUSION: Bifidobacterium Catenulatum ZYB0401 in combination with Lactobacillus Fermentum ZYL0401 could be useful in restoring intestinal microflora and in preventing liver injury in hepatic I/R of rats.
Assuntos
Bifidobacterium , Lactobacillus , Fígado/irrigação sanguínea , Fígado/microbiologia , Probióticos/uso terapêutico , Traumatismo por Reperfusão/microbiologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Técnicas de Cocultura , Suplementos Nutricionais , Modelos Animais de Doenças , Fígado/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Hepatic ischemia/reperfusion injury may induce intestinal microflora imbalance. Salvia miltiorrhiza is effective in promoting blood circulation and counteracting peroxidation in tissues. The aim of the present study was to determine the effects of Salvia miltiorrhiza on intestinal microflora, endotoxemia, and bacterial translocation in rats with hepatic I/R injury. METHODS: Sprague-Dawley rats in specific pathogen free grade were divided into 3 groups: group I(n=6) for sham operation; groups II(n=10) and III(n=7) for liver ischemia for 20 minutes and reperfusion for 22 hours. Group III was also pretreated with 4 ml/day of Salvia miltiorrhiza solution (250 mg/kg) by daily gavage for 7 days. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA) and superoxide dismutase(SOD) in liver tissues, serum endotoxin, intestinal bacterial counts, intestinal mucosal histology and bacterial translocation were studied. RESULTS: The levels of ALT, AST, plasma endotoxin and MDA in liver tissues were decreased more markedly in group III (57.57+/-18.08 U/L, 147.57+/-40.84 U/L, 0.42+/-0.144 EU/ml and 0.52+/-0.19 nmol/mg-prot respectively) in group II(122.8+/-80.12 U/L, 295.9+/-216.92 U/L, 0.80+/-0.262 EU/ml and 0.72+/-0.12 nmol/mg-prot; P<0.05-0.01 respectively). Liver SOD activity was increased more significantly in group III (318.47+/-64.62 U/mg-prot) than in group II(240.76+/-63.67 U/mg-prot, P<0.05). The counts of Bifidobacteria and Bacteroides increased more significantly in group III than in group II, but were similar to those in group I. Bacterial translocation to the kidney in group II was 50%(5/10), whereas no bacterial translocation to the kidney occurred in the other two groups (P<0.01). Ileal mucosal structure was markedly ameliorated in group III as compared with group II. CONCLUSIONS: Salviae miltiorrhiza could partially restore intestinal microflora balance, improve intestinal mucosal integrity, and reduce bacterial translocation and plasma endotoxin in rats with hepatic ischemia/reperfusion injury.