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Crop residue retention and fertilizer application are the main sources of soil nutrient input in fields. Crop residue retention combined with appropriate fertilizer application rates could provide necessary nutrients for crop production under the premise of environmentally friendly conditions. The aim of this study was to clarify the influence of different topdressing nitrogen rates on the soil fungal community in a wheat field under crop residue retention and to evaluate the rationality of nitrogen fertilizer management in winter wheat from the perspective of soil ecological function. On the basis of full straw retention and 150 kg·hm-2 basal nitrogen, treatments with five topdressing nitrogen rates (0, 37.5, 75, 112.5, and 150 kg·hm-2) were set up. The abundance, diversity, structure, and ecological network of soil fungal communities were analyzed using real-time fluorescence quantitative PCR and high-throughput sequencing, and the main soil physical and chemical factors driving the change in soil fungal communities were explored. The results showed that, compared with the no topdressing nitrogen and low topdressing nitrogen rate treatments, high topdressing nitrogen rate treatments increased soil total nitrogen and mineral nitrogen and decreased soil pH, total phosphorus, available phosphorus, and available potassium. Compared with the no topdressing nitrogen treatments, the 37.5-150 kg·hm-2 topdressing nitrogen treatments significantly increased soil fungal community abundance (P<0.05), whereas there was no significant difference among different topdressing nitrogen treatments (P>0.05). The Heip index and Shannon index of soil fungal communities decreased gradually with the increase in topdressing nitrogen rate, and the Sobs index, Heip index, and Shannon index of soil fungal communities in the treatment with 150 kg·hm-2 topdressing nitrogen were significantly lower than those of 0-75 kg·hm-2 topdressing nitrogen treatments (P<0.05). Principal component analysis and similarity analysis showed that there were significant differences in soil fungal community structure under different topdressing nitrogen rate treatments (P<0.05). With the increase in topdressing nitrogen rate, the number of network edges and average number of neighbors of soil fungal ecological network increased first and then decreased, and the network complexity of 37.5 kg·hm-2 topdressing nitrogen treatments was the highest. Compared with 0-75 kg·hm-2 topdressing nitrogen treatments, 112.5 kg·hm-2 and 150 kg·hm-2 topdressing nitrogen treatments increased the characteristic path length of the soil fungal ecological network, whereas it decreased the network density. With the increase in topdressing nitrogen rate, the relative abundance of soil saprotrophs gradually increased, and the pathotroph-saprotroph-symbiotroph relative abundance gradually decreased. Redundancy analysis showed that soil pH, total phosphorus, mineral nitrogen, available phosphorus, and available potassium were the main soil physicochemical factors affecting the soil fungal community structure in the wheat field under different topdressing nitrogen rate treatments. In conclusion, on the basis of straw retention and basal nitrogen, topdressing nitrogen at the wheat jointing stage could change the diversity, structure, and species composition of the soil fungal community, in turn affecting the soil fungal ecological network and function, and high topdressing nitrogen rates could reduce soil fungal community diversity, ecological network complexity, and network density.
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Micobioma , Solo , Solo/química , Triticum , Nitrogênio/análise , Fertilizantes/análise , Fósforo , Minerais , Agricultura/métodosRESUMO
Aging is widely thought to be associated with oxidative stress. Momordica charantia (MC) is a classic vegetable and traditional herbal medicine widely consumed in Asia, and M. charantia polysaccharide (MCP) is the main bioactive ingredient of MC. We previously reported an antioxidative and neuroprotective effect of MCP in models of cerebral ischemia/reperfusion and hemorrhage injury. However, the role played by MCP in neurodegenerative diseases, especially during aging, remains unknown. In this study, we investigated the protective effect of MCP against oxidative stress and brain damage in a D-galactose-induced aging model (DGAM). The Morris water maze test was performed to evaluate the spatial memory function of model rats. The levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were measured and telomerase activity was determined. The results showed that MCP treatment attenuated spatial memory dysfunction induced by D-galactose. In addition, MCP increased antioxidant capacity by decreasing MDA and increasing SOD and GSH levels. MCP treatment also improved telomerase activity in aging rats. Mechanistically, MCP promoted the entry of both Nrf2 and ß-Catenin into the nucleus, which is the hallmark of antioxidation signaling pathway activation. This study highlights a role played by MCP in ameliorating aging-induced oxidative stress injury and reversing the decline in learning and memory capacity. Our work provides evidence that MCP administration might be a potential antiaging strategy.
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Momordica charantia , Telomerase , Ratos , Animais , Galactose/toxicidade , Momordica charantia/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , beta Catenina/metabolismo , Telomerase/metabolismo , Telomerase/farmacologia , Envelhecimento/metabolismo , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Transdução de Sinais , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Superóxido Dismutase/metabolismo , Malondialdeído/metabolismoRESUMO
Orostachys cartilaginous is a traditional herbal medicine and its cell cultures contain large amounts of polysaccharides. To utilize the cultured O.â cartilaginous cells, this study purified the crude polysaccharides of O.â cartilaginous cells by macroporous resin absorption and optimized the purification process in the experiment of orthogonal design with four factors (sample concentration and volume, and eluent concentration and volume) and three levels; the antibacterial and anti-cancer effects of the purified polysaccharides (OTP) were further examined. The results showed that polysaccharide purity reached 95 % in the optimized group, i. e., 1.6â mg/mL of sample (crude polysaccharides) concentration, 3.0 bed volume (BV) of sample volume, 65 % eluent (ethanol) concentration, and 3.0 BV of eluent volume. In the antibacterial experiment, the growth of three bacterial species, i. e., Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis was inhibited by OTP, whereas that of Escherichia coli was not affected; the largest diameter of the inhibitory zone was found on B.â subtilis; the extracellular alkaline phosphatase activity and the electrical conductivity, nucleic acid, and protein levels of B.â subtilis increased after OTP treatment, indicating that the inhibition of B.â subtilis growth was caused by the leakage of cell contents. In the anti-cancer experiment, OTP decreased the cell viabilities of the tested human cancer cells, i. e., AGS (gastric cancer), HCT116 (colon cancer), HepG2 (liver cancer), and HeLa (cervical cancer), and the highest inhibitory effect was on HCT116. OTP promoted HCT116 apoptosis and affected the expression of apoptosis-related proteins, i. e., the expression of B-cell lymphoma-2 decreased and that of bcl-2 associated X protein, cytochrome c, caspase 9 and caspase 3 increased. The findings of the present study suggest that O.â cartilaginous cell cultures have a potential application in food or drug production.
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Plantas Medicinais , Humanos , Antibacterianos/farmacologia , Etanol , Polissacarídeos/farmacologia , Técnicas de Cultura de CélulasRESUMO
Evaluating ecological sustainability and crop productivity of different crop rotation patterns could provide theoretical support for adjusting and optimizing crop planting structure. We set seven treatments with different rotation crops and periods. We used real-time quantitative PCR to determine the abundance of soil bacterial community and 16S rRNA gene amplicon high-throughput sequencing technology to analyze diversity and taxa composition of soil bacterial community. Both soil available nutrients and succeeding wheat yield were measured. The results showed that, compared with the rotation with summer maize, the rotations with summer peanut or soybean in diffe-rent periods reduced soil organic carbon, mineral nitrogen, and available potassium, but significantly increased soil available phosphorus. The 16S rRNA gene copy numbers of soil bacteria in the treatments of rotations with summer peanut or soybean in different periods were significantly decreased, while community richness and diversity were increased. Different rotation crops significantly changed the structure and taxonomic composition of soil bacterial community. Compared with the rotation with summer maize, the rotations with summer soybean in different periods significantly increased the 1000-grain weight and grain yield of succeeding winter wheat. In conclusion, rotations with summer peanut or soybean in different periods could increase soil available phosphorus content and bacterial diversity, and significantly change soil bacterial community structure. In particular, rotation with summer soybean performed best in promoting yield formation of succeeding winter wheat.
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Solo , Triticum , Solo/química , Carbono , RNA Ribossômico 16S/genética , Agricultura/métodos , Produtos Agrícolas , Bactérias/genética , Zea mays/microbiologia , Fósforo/química , Glycine max , Arachis , Produção AgrícolaRESUMO
O. elatus Nakai is a traditional medicine that has been confirmed to exert effective antioxidant and anti-inflammatory functions, and is used for the treatment of different disorders. However, its potential beneficial effects on drug induced hepatotoxicity and relevant molecular mechanisms remain unclear. This study investigated the protective effect and further elucidated the mechanisms of action of O. elatus on liver protection. O. elatus chlorogenic acids-enriched fraction (OEB), which included chlorogenic acid and isochlorogenic acid A, were identified by HPLC-MS/MS. OEB was administrated orally daily for seven consecutive days, followed by a single intraperitoneal injection of an overdose of APAP after the final OEB administration. The effects of OEB on immune cells in mice liver were analyzed using flow cytometry. APAP metabolite content in serum was detected using HPLC-MS/MS in order to investigate whether OEB affects CYP450 activities. The intestinal content samples were processed for 16 s microbiota sequencing. Results demonstrated that OEB decreased alanine aminotransferase, aspartate aminotransferase contents, affected the metabolism of APAP, and decreased the concentrates of APAP, APAP-CYS and APAP-NAC by inhibiting CYP2E1 and CYP3A11 activity. Furthermore, OEB pretreatment regulated lipid metabolism by affecting the peroxisome proliferator-activated receptors (PPAR) signaling pathway in mice and also increased the abundance of Akkermansia and Parabacteroides. This study indicated that OEB is a potential drug candidate for treating hepatotoxicity because of its ability to affect drug metabolism and regulate lipid metabolism.
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Local tumor photothermal treatment with the near-infrared light at the second window (NIR-II) is a promising strategy in triggering the in situ tumor vaccination (ISTV) for cancer therapy. However, limited penetration of photothermal agents within tumors seriously limits their spatial effect in generating sufficient tumor-associated antigens, a key factor to the success of ISTV. In this study, a nano-adjuvant system is fabricated based on the NIR-II-absorbable gold nanostars decorated with hyaluronidases and immunostimulatory oligodeoxynucleotides CpG for ISTV. The nano-adjuvant displays a deep tumor penetration capacity via loosening the dense extracellular matrix of tumors. Upon NIR-II light irradiation, the nano-adjuvant significantly inhibits the tumor growth, induces a cascade of immune responses, generates an obvious adaptive immunity against the re-challenged cancers, boosts the abscopal effect, and completely inhibits the pulmonary metastases. The study highlights an advanced nano-adjuvant formulation featuring deep tumor penetration for NIR-II-triggered ISTV.
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Ouro , Neoplasias , Linhagem Celular Tumoral , Humanos , Raios Infravermelhos , Neoplasias/terapia , Fototerapia , VacinaçãoRESUMO
OBJECTIVE: To investigate a previously uncharacterized function of Sijunzi Decoction (SJZD) in inhibition of gastric cancer stem cells (GCSCs). METHODS: MKN74 and MKN45, two CD44 positive gastric cancer cell lines with stem cell properties were used. The cells were divided into 2 groups. Treatment group was treated with SJZD (1-5 mg/mL) for indicated time (48 h-14 days). The control group was treated with equal volume of phosphate buffered saline. Cell Counting Assay Kit-8 were used to measure cell viability. Spheroid colony formation and GCSCs marker expression were performed to determine GCSCs stemness. Cell fractionation and chromatin immunoprecipitation assays were used to assess the distribution and DNA-binding activity of ß-catenin after SJZD treatment, respectively. RESULTS: SJZD treatment repressed cell growth and induced apoptosis in MKN74 and MKN45 cell lines (P<0.05). Moreover, SJZD dramatically inhibited formation of spheroid colony and expression of GCSC markers in GC cells (P<0.05). Mechanistically, SJZD reduced nuclear accumulation and DNA binding activity of ß-catenin (P<0.05), the key regulator for maintaining CSC stemness. CONCLUSION: SJZD inhibits GCSCs by attenuating the transcriptional activity of ß-catenin.
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Medicamentos de Ervas Chinesas , Neoplasias Gástricas , Linhagem Celular Tumoral , DNA/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Células-Tronco Neoplásicas/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , beta Catenina/metabolismoRESUMO
Objective: Epigenetics, including DNA methylation, histone modification, and posttranscriptional regulation of microRNAs, is the study of heritable changes in gene expression that do not include DNA-sequence alterations. Epigenetics has become a new strategy for basic and clinical research on acupuncture in the last decade. The aim of this research update was to summarize the epigenetic mechanisms of angiogenesis induced by acupuncture treatment in ischemic heart diseases. Materials and Methods: The current authors' group has been working to illustrate the mechanism of acupuncture from an epigenetics perspective, which has shed new lights on the mechanisms and applications of acupuncture in cardiovascular diseases. This article summarizes the group's new findings in animal models as well as in patients with chronic stable angina. Progress since 2011 in other teams' research in this field is also discussed in this article. Conclusions: Acupuncture could regulate histone modifications and could rescue patients who sustain ischemic injuries. This treatment could possibly work through promoting angiogenesis.
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italic>Bulbophyllum orchids are popular for its ornamental appearance and great medicinal values. However, there is still a lack of research on phylogenetic relationship and species identification for this genus. In this study, the plastome sequences of three medicinal Bulbophyllum orchids (Bulbophyllum affine, Bulbophyllum pectinatum, Bulbophyllum funingense) were sequenced and analyzed. After assembly and annotation, it was found that the plastomes of Bulbophyllum plants encoded a total of 108 genes, including 74 protein-coding genes, 30 tRNA genes and 4 rRNA genes. Based on the analysis of mVISTA and comparison between junctions, it was found that the plastome structure of Bulbophyllum orchids was relatively conserved, and the variation mainly existed in the non-coding regions. Phylogenetic analysis showed that Bulbophyllum orchids were closely related to Dendrobium orchids. SSR analysis of Bulbophyllum showed that most SSRs were located in the intergenic spacer and had the most single nucleotide repeats. In addition, based on the comparative analysis of non-coding sequences, a total of 10 high-variability sequences were screened out, among which the combination of five non-coding region sequences, including psbI-trnS, psbC-trnS, clpP-ex1-psbB, psaJ-rpl33, rpl33-rps18, had the highest sequence variability and could be used in the species identification study of medicinal plants of Bulbophyllum. In conclusion, this study provides a theoretical basis for phylogenetic relationship and species identification of Bulbophyllum orchids through the comparative analysis of plastome sequences of three medicinal plants of the genus Bulbophyllum.
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Escherichia coli phytase appA, which hydrolyzes phytate, has been widely applied as an important feed supplement, but its resistance to trypsin needs to be improved. Six putative solvent-accessible amino acid residues (K74, K75, K180, R181, K183, and K363), which could be easily attacked by trypsin, were selected to improve trypsin tolerance of Escherichia coli phytase appA. Inspection of the three-dimensional structure and computational design via hydrogen bond analysis, six optimal mutation sites of K74D/K75Q/K180N/R181N/K183S/K363N, which strengthened the hydrogen bonding, were performed to generate three mutants. Results showed that the most beneficial mutant appA-M6 had a specific activity of 3262 U/mg with molecular weight of approximately 52-55 kDa. Similar to appA-WT, the optimal pH (4.5) and temperature (60 °C) of appA-M6 were unchanged. Compared with appA-WT, appA-M6 showed a significant enhancement (p < 0.05) in resistance to trypsin and a 3.8 °C increase in melting temperature (Tm). We concluded that introduction of hydrogen bonds and N-glycosylation modification resulted in decreased enzyme flexibility and increased the enzyme stability against proteolysis and thermal denaturation. The mutant appA-M6 generated in this study could be applied for the large-scale commercial production of phytase and thus could benefit the food and feed industry.
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6-Fitase/química , 6-Fitase/genética , Fosfatase Ácida/química , Fosfatase Ácida/genética , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Escherichia coli/enzimologia , 6-Fitase/metabolismo , Fosfatase Ácida/metabolismo , Motivos de Aminoácidos , Estabilidade Enzimática , Escherichia coli/química , Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Glicosilação , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Engenharia de Proteínas , Temperatura , Tripsina/químicaRESUMO
Field surveys and literatures show that Polygonati Rhizome (Huangjing) was firstly recorded in Shen Nong&s Herbal Classic, and widely used as a medicinal and edible plant. It has a long history of cultivation, and the researches on chemistry have made some progress. The future development is prospected on health market. But the Polygonati Rhizome industry has faced a lot of problems, including the resource depletion, unstable quality, low-tech in cultivation and germplasm confusion, unclear of functional composition, decentralized, small scaled and primary processing products. The suggestion for sustainable development are listed below. First, the relevant researches should focused on material basis and biological mechanism of core effects. To speed up the selection and breeding of improved varieties, ensure the supply of high-quality seedlings and eliminate the unauthentic species are the most important measures. Secondly, to strengthen the conservation and rational use of wild resources, break through the key technologies of high-quality artificial cultivation on light regulation, site control, density control and precision harvesting are also very important. Thirdly, to reveal the toxicity-reducing-and-efficacy-enhancing mechanism of processing, optimize the parameters and setup the standard operating procedure are indispensable. Fourthly, that full advantage of the root, leaf, flower and fruit resources should be strengthened for enlarged health products based on the development of exact functional factors. Above all, Polygonati Rhizome could be a growing market in the future driven by the technological innovation, cultural creativity, integration of three industries, brand strategy and internet+technique.
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Rizoma , Melhoramento Vegetal , Folhas de Planta , Polygonatum , Desenvolvimento SustentávelRESUMO
As a classical external treatment of traditional Chinese medicine, blistering moxibustion has significant curative effect on asthma, rheumatoid arthritis and other immune disorders, which suggests that it has certain immunoregulation effect. When stimulated, skin immune system evokes innate immune or acquired immune systems, including dendritic cells (DC), a type of crucial cell related to acquired immunity. From the classification and function of DC, especially the differentiation, migration and maturation of DC in local skin after blistering moxibustion. This article was to discuss the possible ways of immunoregulation of DC in local skin after blistering moxibustion, so as to provide reference for the study on immunoregulatory mechanism of blistering moxibustion.
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The Three Gorges Reservoir (TGR), which is the largest water conservancy project ever built in tne world, produced a drawdown area of about 348.93 km2 because of water level control. The biological geochemical cycle of the soil in the drawdown zone has been changed as the result of long-term winter flooding and summer drought and vegetation covering. The loss of soil nitrogen in the drawdown zone poses a threat to the water environmental in TGR. Pengxi river, is an important anabranch, which has the largest drawdown area has been selected in the present study. The four typical vegetation, contained Cynodon dactylon, Cyperus rotundus, Anthium sibiricum and Zea mays L. as the control, were studied to measure nutrient characteristics and nitrogen forms of rhizosphere and non-rhizosphere soils in three distribution areas with different soil types (paddy soil, purple soil and fluvo-aquic soils). The variables measured included organic matter (OM), total nitrogen (TN), total phosphorus (TP), total potassium (TK), hydrolysis N, available P and available K, pH, ion-exchangeable N (IEE-N), weak acid extractable N (CF-N) , iron-manganese oxides N (IMOF-N), organic matter sulfide N (OSF-N), added up four N forms for total transferable N (TF-N) and TN minus TF-N for non-transferable N (NTF-N). The results showed: (1) pH of rhizosphere soil was generally lower than that of non-rhizosphere soil under different vegetation in different type soils because the possible organic acid and H+ released form plant roots and cation absorption differences, and the OM, TP, TN and hydrolysis N of rhizosphere soil were generally higher than those of non-rhizosphere soil, and that the enrichment ratio (ER) of all the four nutrient indicators showed Cyperus rotundus > Cynodon dactylon > Zea mays L. > Anthium sibiricum. Available P showed enrichment in the rhizosphere of three natural vegetations but lose under corn, and available K, TK showed different ER in different conditions. (2) IEF-N CF-N, IMOF-N, OSF-N and TF-N of rhizosphere soil were generally higher than those of non-rhizosphere soil, but the TF-N to TN ratio in rhizosphere of Cyperus rotundus and Cynodon dactylon were lower than those of non-rhizosphere soil, and in rhizosphere of Anthium sibiricum and Zea mays L. were higher, the rhizosphere effect of different vegetations on the N cycle was significant difference. (3) the correlation between nutrient characteristics and nitrogen forms was evaluated to explore the influence factor for the N forms changing. There was a significant correlation between soil OM and four N forms, TP was significantly correlated with CF-N, OSF-N, TF-N, and soil available P content was significantly negatively correlated with IMOF-N, OSF-N, TF-N and TN. Our research could provide that the drawdown zone covered with Cyperus rotundus and Cynodon dactylon was better than Anthium sibiricum and Zea mays L. to improve soil N holding and fixation. The vegetation recovery in the drawdown zone should consider the rhizosphere effect of different vegetations on N cycle.
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Nitrogênio/química , Rizosfera , Solo/química , China , Cynodon , Cyperus , Secas , Inundações , Fósforo/química , Raízes de Plantas , Rios , Zea maysRESUMO
Reducing process cost of the bioconversion of lignocellulosic is a challenge. In China, abundant acidic wastewater from monosodium glutamate production is difficult to treat, leading to serious water pollution. In this study, acidic liquid (ALC) and solid residue components (SC) obtained from the wastewater were used in pretreatment and cellulase production, respectively, to evaluate their potential in bioconversion of corn stover. Optimum pretreatment conditions (170 degrees C, 60min, 0.75% ALC) were identified by a central composite design method. There were little difference in the chemical components and digestibility (above 84%) of between ALC and H(2)SO(4)-treated corn stover, and amounts of HMF and furfural in liquor after pretreatment with ALC and H(2)SO(4) under optimum conditions. SC can be substituted for (NH(4))(2)SO(4) in liquor fermentation to produce cellulase with comparable filter paper (about 10.7U/ml) and beta-glucosidase (about 2.7U/ml) activities.
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Celulase/metabolismo , Resíduos Industriais/prevenção & controle , Penicillium/enzimologia , Extratos Vegetais/metabolismo , Glutamato de Sódio/química , Poluentes da Água/química , Zea mays/química , Biodegradação Ambiental , Estudos de Viabilidade , Extratos Vegetais/química , Purificação da Água/métodosRESUMO
BACKGROUND: Due to the long duration of treatment and the emergence of multidrug-resistant strains, new antitubercular agents are urgently needed. I2906, as a novel lead, was screened and tested for efficacy in vitro and in vivo. METHODS: To determine the efficacy of I2906,the minimum inhibitory concentrations against Mycobacterium tuberculosis and cytotoxicity were tested, and its in vivo activities were assessed by administering it to mice infected with M. tuberculosis H37Rv or multidrug-resistant strain. RESULTS: Under in vitro conditions, I2906 showed excellent antimycobacterial activities and low cytotoxicity. In a murine model infected with M. tuberculosis H37Rv, the reductions on bacterial loads of both lungs and spleen were statistically significant (p < 0.05) between I2906-treated mice and untreated controls after 4 weeks. Further, the colony-forming unit counts in the lungs were dramatically lower (p < 0.05) than that of isoniazid-treated mice by the addition of I2906 after 8 weeks. Moreover, survival rate was increased by I2906 treatment. For multidrug-resistant strain infection, bacterial counts were reduced significantly in the lungs and spleen due to I2906 treatment in comparison with data from untreated controls (p < 0.05). CONCLUSIONS: I2906 displayed potential antimicrobial activities against M. tuberculosis H37Rv and drug-resistant strains in vitro and in vivo, and could improve efficacy of isoniazid in vivo.
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Antituberculosos/uso terapêutico , Hidrazinas/farmacologia , Hidrazinas/toxicidade , Mycobacterium tuberculosis/efeitos dos fármacos , Quinolonas/farmacologia , Quinolonas/toxicidade , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Animais , Antituberculosos/sangue , Antituberculosos/farmacologia , Antituberculosos/toxicidade , Linhagem Celular Tumoral , Contagem de Colônia Microbiana , Avaliação Pré-Clínica de Medicamentos , Feminino , Haplorrinos , Humanos , Hidrazinas/sangue , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/patogenicidade , Quinolonas/sangue , Baço/microbiologia , Análise de Sobrevida , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/patologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologiaRESUMO
In order to identify new and potent candidate drugs to treat tuberculosis, a library of compounds was screened, and (S,S)-N,N'-bis-[3-(2,2',6,6'-tetramethylbenzhydryloxy)-2-hydroxy-propyl]-ethylenediamine (S2824) was identified as a hit in the screen. This research discusses our efforts to synthesize and test 30 analogs of this hit for activity against Mycobacterium tuberculosis. Two compounds with homopiperazine ring possess high in vitro activity against drug sensitive and resistant M. tuberculosis with MICs 0.78-3.13 microg/mL (or 1.22-4.88 microM).
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Antituberculosos/síntese química , Azepinas/síntese química , Compostos Benzidrílicos/síntese química , Etilenodiaminas/síntese química , Tuberculose/tratamento farmacológico , Antituberculosos/química , Antituberculosos/toxicidade , Azepinas/química , Azepinas/toxicidade , Compostos Benzidrílicos/química , Compostos Benzidrílicos/toxicidade , Avaliação Pré-Clínica de Medicamentos , Farmacorresistência Bacteriana , Etilenodiaminas/química , Etilenodiaminas/toxicidade , Mycobacterium tuberculosis/efeitos dos fármacosRESUMO
AIM: Polypeptide from Chlamys farreri (PCF, molecular mass is 879) is a new marine polypeptide compound isolated from Chlamys farreri. This study investigates the possible protective roles and the mechanism of PCF against ultraviolet B (UVB)-induced apoptosis in murine thymocytes. METHODS: The rate of apoptosis and caspase-3 activation was measured by flow cytometry. The expression of stress-response genes c-fos and c-jun was observed by RT-PCR. Western blot analysis was performed to determine the release of cytochrome c. RESULTS: It was found that UVB induced murine thymocyte death. The cells treated with UVB showed an increase in cytochrome c release, caspase-3 activity, as well as in the expression of c-fos and c-jun. In addition, all were involved in UVB-induced cell apoptosis. CONCLUSION: Our present observations pointed to the ability of PCF to avert UVB-induced apoptosis in thymocytes by modulating c-fos and c-jun expression, cytochrome c release, and the consequent activation of caspase-3, which were essential components of the UV-induced cell apoptotic pathway. The results suggested that PCF is a promising protective substance against UV radiation.
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Materia Medica/farmacologia , Pectinidae/química , Peptídeos/farmacologia , Timo/citologia , Raios Ultravioleta , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Western Blotting , Caspase 3/metabolismo , Células Cultivadas , Citocromos c/metabolismo , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/efeitos da radiação , Citometria de Fluxo , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/efeitos da radiação , Genes fos/genética , Genes jun/genética , Materia Medica/isolamento & purificação , Camundongos , Peptídeos/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Timo/efeitos dos fármacos , Timo/efeitos da radiaçãoRESUMO
Radix Ranuncoli Ternati is clinically effective traditional Chinese medicine for multidrug resistant tuberculosis. Its active components and mechanism of action remain unsolved. Two dimensional gel electrophoresis (2-DE) was employed to address this problem. Globlal proteome of Mycobacterium tuberculosis untreated and treated with Radix Ranuncoli Ternati were compared, and 22 protein spots were found to be expressed differentially. 3 protein spots which remarkably decreased in Mycobacterium tuberculosis treated with Radix Ranuncoli Ternati were subjected to matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) analysis. The data obtained from peptide mass finger printing were used for database search. The 3 protein spots in gel were identified as cysA2 (thiosulfate sulfurtransferase), tsf (elongation factor EF-Ts) and hspX (heat shock protein X). These data provide insights into the changed global protein patterns of Mycobacterium tuberculosis treated with Radix Ranuncoli Ternati and may prove useful for further study in the mechanism in how Radix Ranuncoli Ternati influence the life of Mycobacterium tuberculosis. The differentially expressed proteins may be potential novel antituberculosis drug targets.
Assuntos
Proteínas de Bactérias/análise , Medicina Tradicional Chinesa , Mycobacterium tuberculosis/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proteoma , Antígenos de Bactérias/análise , Eletroforese em Gel Bidimensional , Mycobacterium tuberculosis/química , Fator Tu de Elongação de Peptídeos/análise , Fatores de Alongamento de Peptídeos/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
AIM: Liver fibrosis is a common pathological process of chronic liver diseases. Activation of hepatic stellate cells (HSCs) is the key issue in the occurrence of liver fibrosis. In this study, we observed the inhibitory action of rat serum containing Biejiajian oral liquid (BOL), a decoction of turtle shell, on proliferation of rat HSCs, and to explore the anti-hepatofibrotic mechanisms of BOL. METHODS: A rat model of hepatic fibrosis was induced by subcutaneous injection of CCl(4). Serum containing low, medium and high dosages of BOL was prepared respectively. Normal and fibrotic HSCs were isolated and cultured. The effect of sera containing BOL on proliferation of HSCs was determined by (3)H-TdR incorporation. RESULTS: The inhibitory rate of normal rat HSC proliferation caused by 100 mL/mL sera containing medium and high dosages of BOL showed a remarkable difference as compared with that caused by colchicine (medium dosage group: 34.56+/-4.21% vs 29.12+/-2.85%, P<0.01; high dosage group: 37.82+/-1.32% vs 29.12+/-2.85%, P<0.01). The inhibitory rate of fibrotic rat HSC proliferation caused by 100 mL/L serum containing medium and high dosages of BOL showed a remarkable difference as compared with that caused by colchicine (medium dosage group: 51.31+/-3.14% vs 38.32+/-2.65%, P<0.01; high dosage group: 60.15+/-5.36% vs 38.32+/-2.65%, P<0.01). The inhibitory rate of normal rat HSC proliferation caused by 100 mL/L and 200 mL/L sera containing a medium dosage of BOL showed a significant difference as compared with that caused by 50 mL/L (100 mL/L group: 69.02+/-9.96% vs 50.82+/-9.28%, P<0.05; 200 mL/L group: 81.78+/-8.92% vs 50.82+/-9.28%, P<0.01). The inhibitory rate of fibrotic rat HSC proliferation caused by 100 mL/L and 200 mL/L sera containing a medium dosage of BOL showed a significant difference as compared with that caused by 50 mL/L (100 mL/L group: 72.19+/-10.96% vs 61.38+/-7.16%, P<0.05; 200 mL/L group: 87.16+/-8.54% vs 61.38+/-7.16%, P<0.01). CONCLUSION: Rat serum containing BOL can inhibit proliferation of rat HSCs, and the inhibition depends on the dosage and concentration of BOL. The inhibitory effect on HSC proliferation is one of the main anti-hepatofibrotic mechanisms of BOL.