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We investigated the influence of DNA fragmentation index (DFI) on in vitro fertilization (IVF), embryo transfer (ET), and intracytoplasmic sperm injection (ICSI). We analyzed the semen parameters of 61 cycles in infertile couples undergoing IVF-ET and ICSI and determined DFI by sperm chromatin dispersion testing. Based on DFI, the patients were differentiated into a control group (DFI < 25%, n = 35) and a test group (DFI ≥ 25%, n = 26). Flow cytometry and immunofluorescence were used to investigate the extent of sperm reactive oxygen species (ROS) and apoptosis. We also investigated the effect of DFI on pregnancy outcomes of IVF-ET/ICSI. DFI was negatively related to sperm motility and positively correlated with ROS and apoptosis (P < 0.05). Abnormally elevated DFI reduced the rate of transplantable, high-quality embryos, implantation, clinical pregnancy, delivery, and live birth after IVF-ET, and increased the chance of early abortion per transfer cycle (P < 0.05). However, there was no significant correlation between DFI and fertilization rate, cleavage rate, transplantable rate, high-quality embryo rate, implantation rate, clinical pregnancy rate, early abortion rate, delivery rate and live birth rate when assisted by ICSI (P > 0.05). Sperm DNA integrity is crucial for fertilization and the development of healthy offspring. ROS may increase the level of DFI by inducing apoptosis in sperm.
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Sanggenon C is a flavonoid extracted from the root bark of white mulberry, which is a traditional Chinese medicine with anti-inflammatory, antioxidative, and antitumor pharmacological effects. In this study, sanggenon C was found to inhibit human gastric cancer (GC) cell proliferation and colony formation, induce GC cell cycle arrest in the G0-G1 phase, and promote GC cell apoptosis. Moreover, sanggenon C was found to decrease the level of mitochondrial membrane potential in GC cells and inhibit mitochondrial fission. Mechanistically, RNA sequencing, bioinformatics analysis, and a series of functional analyses confirmed that sanggenon C inhibited mitochondrial fission to induce apoptosis by blocking the extracellular regulated protein kinases (ERK) signaling pathway, and constitutive activation of ERK significantly abrogated these effects. Finally, sanggenon C was found to suppress the growth of tumor xenografts in nude mice without obvious side effects to the vital organs of animals. This study reveals that sanggenon C could be a novel therapeutic strategy for GC treatment.
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Dinâmica Mitocondrial , Neoplasias Gástricas , Camundongos , Animais , Humanos , Neoplasias Gástricas/tratamento farmacológico , Camundongos Nus , Proteínas Quinases/farmacologia , Apoptose , Carcinogênese , Proliferação de Células , Linhagem Celular TumoralRESUMO
Originally considered to be a plant pathogen, reports of phaeohyphomycosis due to Curvularia lunata (C. lunata) in animals and humans are increasing. However, studies on the pathogenesis, virulence, and epidemiology of C. lunata have rarely been discussed. In the present study, BALB/c mice were experimentally inoculated with C. lunata suspension by different routes and the course of infection was evaluated. In addition, the in vitro antifungal susceptibility of C. lunata against six commonly used antifungals was evaluated using the microdilution method. Inoculation resulted in skin lesions in animals inoculated intraperitonially and subcutaneously. Infection was confirmed by both mycological and histopathologic examination. C. lunata spores and hyphae were detected in the histopathologic sections stained with hexamine silver staining. In addition, voriconazole (VRC) demonstrated greater activity against C. lunata when compared to the other antifungals, whereas fluconazole (FLC) was the least active antifungal with a minimum inhibitory concentration (MIC) range of 8-16 µg/mL. Further studies are necessary to understand the pathogenicity of C. lunata and uncover the mystery of this fungus.
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Not required for Clinical Vignette.
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Doenças em Gêmeos/diagnóstico , Doença de Hashimoto/diagnóstico , Vasculite por IgA/diagnóstico , Criança , Doenças em Gêmeos/complicações , Feminino , Doença de Hashimoto/complicações , Humanos , Vasculite por IgA/complicações , GêmeosRESUMO
In the rhizosphere, plant root exudates can mediate the toxicity of antibiotics on microorganisms, yet the mechanisms are poorly understood. To simulate the antibiotic contamination of global rivers and lakes, the current study investigated the effects of two antibiotics (ofloxacin at 8.69 × 104 ng L-1 and tetracycline at 8.62 × 104 ng L-1) and their binary combination (8.24 × 104 ng L-1 ofloxacin and 7.11 × 104 ng L-1 tetracycline) on bacterial communities in micro-polluted constructed wetlands with and without artificial root exudates. The two antibiotics had no significant effects on the removal of excess carbon and nitrogen from the microcosms treated with and without exudates. Furthermore, with regard to bacterial community structure, antibiotic exposure increased the bacterial richness of bulk and exudate treated microcosms (P < 0.05). However, a significant increase (P < 0.05) in bacterial diversity elicited by ofloxacin and antibiotic mixture exposure was only observed in microcosms with exudates. In exudate treated microcosms, ofloxacin promoted the relative abundance of Arthrobacter spp., which are ofloxacin-resistant bacterial species, which significantly varied from what was observed in microcosms free of exudates. Moreover, tetracycline, ofloxacin and their combination all significantly increased the relative abundance of nitrogen cycling bacteria Rhizobacter spp. and Rhizobium spp., and decreased the relative abundance of antibiotic-resistant bacteria Pseudomonas spp. Simultaneously, with regard to bacterial community functions, the functional profiles (Kyoto Encyclopedia of Genes and Genomes) showed that the pathways of amino acid and carbohydrate metabolism were enhanced by antibiotics in microcosms with exudates. The findings illustrate that antibiotics not only alter the bacterial structure and composition but also change their functional properties in constructed wetlands, and these interruption effects could be affected by root exudates of plants, which may further reveal the ecological implication of plants in constructed wetlands.
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Antibacterianos , Microbiota , Rizosfera , Áreas Alagadas , Antibacterianos/toxicidade , Microbiota/efeitos dos fármacos , Nitrogênio , Raízes de Plantas/microbiologiaRESUMO
The aim of this paper was to study the influence of triptolide in the immune response pathways of acquired immune deficiency syndrome( AIDS). Target proteins of triptolide and related genes of AIDS were searched in PubChem and Gene databases on line. Molecular networks and canonical pathways comparison analyses were performed by bioinformatics software( IPA). There were 15 targets proteins of triptolide and 258 related genes of AIDS. Close biological relationships of molecules of triptolide and AIDS were established by networks analysis. There were 21 common immune response pathways of triptolide and AIDS,including neuroinflammation signaling pathway,Th1 and Th2 activation pathway and role of pattern recognition receptors in recognition of bacteria and viruses. Triptolide stimulated immune response pathways by the main molecules of IFNγ,JAK2,NOD1,PTGS2,RORC. IFNγ is the focus nodes of triptolide and AIDS,and regulates genes of AIDS directly or indirectly. Triptolide may against AIDS by regulating molecules IFNγ in immune response pathways.
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Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Diterpenos/farmacologia , Interferon gama/genética , Fenantrenos/farmacologia , Síndrome da Imunodeficiência Adquirida/imunologia , Biologia Computacional , Compostos de Epóxi/farmacologia , Redes Reguladoras de Genes , Humanos , Receptores de Reconhecimento de Padrão/imunologia , Transdução de Sinais , Linfócitos T/imunologiaRESUMO
Rosai-Dorfman disease (RDD) with isolated central nervous system (CNS) involvement is an extremely rare disease. Most RDD of the CNS present as dural-based mass mimicking meningioma and other common lesions, which makes preoperative accurate diagnosis of great difficulty. We searched the pathology database in our hospital and 3 cases of RDD with isolated CNS involvement were finally included in our study. Radiological and clinical findings of these three cases were retrospectively analyzed. The lesions of 2 cases were dura-based against the cerebral convexity, presenting as a sheet-shaped thickened dura mater, another case was located just across the cerebral falx, the dural display in the center was intact. The 3 cases showed low signal intensity on T2-weighted image, obviously enhanced, significantly surrounding edema and finger-like protuberance but no invasion of the brain parenchyma or no sign of hyperplasia or sclerosis of the surrounding cranial bones. In conclusion, when we come across a disease that mimicking meningioma, especially when it manifests as the above radiological features, we should considered it might be a kind of proliferative disease of the meninges, such as RDD.
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Doenças do Sistema Nervoso Central/diagnóstico por imagem , Doenças do Sistema Nervoso Central/patologia , Transtornos Linfoproliferativos/diagnóstico por imagem , Transtornos Linfoproliferativos/patologia , Meninges/diagnóstico por imagem , Meninges/patologia , Adulto , Encéfalo/diagnóstico por imagem , Doenças do Sistema Nervoso Central/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Transtornos Linfoproliferativos/cirurgia , Masculino , Meninges/cirurgia , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To explore the molecular-level mechanism on the hematopoiesis effect of Angelicae sinensis Radix (ASR) with systems-based interactome analysis. METHODS: This systems-based interactome analysis was designed to enforce the workflow of "ASR (herb)âcompoundâtarget proteinâinternal protein actionsâending regulated protein for hematopoiesis". This workflow was deployed with restrictions on regulated proteins expresses in bone marrow and anemia disease and futher validated with experiments. RESULTS: The hematopoiesis mechanism of ASR might be accomplished through regulating pathways of cell proliferation towards hemopoiesis with cross-talking agents of spleen tyrosine kinase (SYK), Janus kinase 2 (JAK2), and interleukin-2-inducible T-cell kinase (ITK). The hematopoietic function of ASR was also validated by colony-forming assay performed on mice bone marrow cells. As a result, SYK, JAK2 and ITK were activated. CONCLUSION: This study provides a new approach to systematically study and predict the therapeutic mechanism for ASR based on interactome analysis towards biological process with experimental validations.
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Angelica sinensis/química , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Hematopoese/efeitos dos fármacos , Raízes de Plantas/química , Animais , Medula Óssea/efeitos dos fármacos , Janus Quinase 2/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Tirosina Quinases/metabolismo , Quinase Syk/metabolismoRESUMO
OBJECTIVE: To observe the effect of norcantharidin (NCTD) on collagen-induced arthritis (CIA) rats. METHODS: Sixty Sprague-Dawley(SD) rats were randomly divided into 6 groups (n=10): normal group, CIA model group(model group), NCTD low-dose group [1.35 mg/(kgâ¢d)], NCTD middle-dose group [2.7 mg/(kgâ¢d)], NCTD high-dose group [5.4 mg/(kgâ¢d)] and methotrexate (MTX) group [1.8 mg/(kg/w)]. Anesthetized rats were sacrificed by luxation of cervical vertebra after 4 weeks of administration. The arthritis scores were evaluated twice a week. The pathological changes in the ankle joints of rats were observed by hematoxylin-eosin (H&E) staining. The serum levels of interleukin (IL) 1ß, IL-6, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), IL-17 and transform growth factor (TGF) ß were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression of retinoid-related orphan nuclear receptorγt (RORγt) and forkhead box P3 (Foxp3) in peripheral blood lymphocytes were confirmed by real-time polymerase chain reaction. RESULTS: MTX and high-dose NCTD not only decreased the arthritis scores but also alleviated the pathological changes in CIA rats' ankle joints compared with the model group (P<0.05 or P<0.01). All doses of NCTD significantly inhibited the serum levels of IL-6, IL-17 and TNF-α in CIA rats (P<0.05). Only middle- and high-dose of NCTD prominently decreased serum IL-1ß and TGF-ß levels of CIA rats (P<0.05). However, NCTD has no effect on vascular endothelial growth factor (VEGF) level in CIA rats. The Foxp3 mRNA expression in all NCTD groups were increased significantly than in the model group (P<0.05). The mRNA expression of RORγt in NCTD high-dose group was decreased apparently in comparison with the model group (P<0.05). CONCLUSIONS: NCTD showed therapeutic effect on CIA rats by inhibition of cytokines and regulation of Th17/Treg cells.
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Artrite Experimental/tratamento farmacológico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Animais , Artrite Experimental/sangue , Artrite Experimental/patologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Citocinas/sangue , Fatores de Transcrição Forkhead/metabolismo , Articulações/efeitos dos fármacos , Articulações/patologia , Masculino , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-DawleyRESUMO
Objective: Triptolide (TL), a natural product isolated from Tripterygium wilfordii Hook F (TwHF), shows potent anticancer effects in vitro and in vivo. We aimed to summary the biochemical mechanisms through which TL has been shown to induce apoptosis, autophagy and inhibit angiogenesis in pancreatic cancer (PC). Methods: We undertook a systematic review of preclinical evidence. We searched electronic databases. The potential mechanisms and the underlying signaling pathways have been accumulated as well. Results: We screened 116 abstracts for eligibility and included 17 preclinical studies in the analysis. Details of the animals and cell lines were provided in 16 studies (94.1%). Six studies (75.0%) randomly assigned animals to treatment or control groups and only 1 study (12.5%) reported on blinding. The majority of the TL's research field has focused on its pro-apoptotic effects through downregulation of inhibitory pathways and upregulation of apoptotic pathways. The studies have shown that TL is effective both in vitro and in vivo against PC cells. Conclusion: This study provides a systematic summary of TL's anti-pancreatic cancer profile and the underlying mechanisms of with special emphasis on the apoptosis, autophagy, angiogenesis and related molecular pathways. Improved study quality in terms of treatment allocation methods reporting, randomization and blinding will accelerate needed progress toward trials.
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[This corrects the article on p. 402 in vol. 7, PMID: 27877128.].
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Objective:Tripterygium wilfordii Hook F (TwHF) is a widely used and effective treatment for inflammatory diseases. There have been concerns about its toxicity but no adequate synthesis of the evidence for adverse events (AEs). We aimed to undertake a clinically informative, systematic safety profile of TwHF. Methods: We undertook a systematic review and meta-analysis of experimental studies and observational studies. We searched electronic databases and conference abstracts. Safety outcomes were rates of common AEs. Results: We screened 4137 abstracts for eligibility and included 594 studies in the analysis. The overall incidence of AEs was 26.7% (95% CI 24.8%, 28.8%) in 23,256 TwHF users. The estimates did vary markedly when stratified by specific study types. The incidence of gastrointestinal symptoms, adverse reproductive outcomes, adverse skin reactions, hematologic events and cardiovascular events were 13.3% (95% CI 11.9%, 14.9%), 11.7% (95% CI 10.3%, 13.3%), 7.8% (95% CI 6.3-9.5%), 6.5% (95% CI 5.7-7.4 %) and 4.9% (95% CI 1.6 %, 14.3 %), respectively. The prevalence of irregular menstruation (IM) was increased in patients taking TwHF compared with those given control (odds ratio [OR] 4.65, 95% CI 3.08 to 7.03). TwHF use has lower risk of weight gain (OR 0.12 [95% CI 0.04 to 0.39]) and hair loss (OR 0.37 [95% CI 0.18 to 0.78]). Furthermore, long-term aspirin use (>6 months) has a higher AEs incidence (31.0% [95% CI 24.5%-38.5%]). Conclusion: Our findings suggest that more than one in four patients who were taking TwHF had experienced AEs. A clear need exists for improved understanding of contributing risk factors, as well as of prevention and management strategies to improve patients' tolerance for TwHF.
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BACKGROUND: Diazotrophic (nitrogen-fixing) Gram-positive and endospore-formed Paenibacillus spp. have potential uses as a bacterial fertilizer in agriculture. The transcriptional analysis of nitrogen fixation in Paenibacillus is lacking, although regulation mechanisms of nitrogen fixation have been well studied in Gram-negative diazotrophs. RESULTS: Here we report a global transcriptional profiling analysis of nitrogen fixation in Paenibacillus sp. WLY78 cultured under N2-fixing condition (without O2 and NH4(+)) and non-N2-fixing condition (air and 100 mM NH4(+)). The nif (nitrogen fixation) gene operon composed of 9 genes (nifBHDKENXhesAnifV) in this bacterium was significantly up-regulated in N2-fixing condition compared to non-N2-fixing condition, indicating that nif gene transcription is strictly controlled by NH4(+) and O2. qRT-PCR confirmed that these nif genes were differently expressed. Non-nif genes specifically required in nitrogen fixation, such as mod, feoAB and cys encoding transporters of Mo, Fe and S atoms, were coordinately transcribed with nif genes in N2-fixing condition. The transcript abundance of suf operon specific for synthesis of Fe-S cluster was up-regulated in N2-fixing condition, suggesting that Sul system, which takes place of nifS and nifU, plays important role in the synthesis of nitrogenase. We discover potential specific electron transporters which might provide electron from Fe protein to MoFe protein of nitrogenase. The glnR whose predicted protein might mediate nif transcription regulation by NH4(+) is significantly up-regulated in N2-fixing condition. The transcription levels of nitrogen metabolism and anaerobic respiration were also analyzed. CONCLUSIONS: The nif gene operon (nifBHDKENXhesAnifV) in Paenibacillus sp. WLY78 is significantly up-regulated in N2-fixing condition compared to non-N2-fixing condition. Non-nif genes specifically required in nitrogen fixation were also significantly up-regulated in N2-fixing condition. Fur and Fnr which are involved in anaerobic regulation and GlnR which might mediate nif gene transcription regulation by NH4(+) were significantly up-regulated in N2-fixing condition. This study provides valuable insights into nitrogen fixation process and regulation in Gram-positive firmicutes.
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Genoma Bacteriano , Fixação de Nitrogênio , Paenibacillus/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Óperon , Paenibacillus/fisiologiaRESUMO
To explore the pharmacological mechanism of glycyrrhizin with series methods of systems pharmacology, main diseases related to glycyrrhizin were obtained by text mining tool; and the target proteins of glycyrrhizin were obtained via the database of Polysearch and PubChem. Then, the target proteins interaction network of glycyrrhizin was built using the software called Cytoscape. Next, the protein groups related to glycyrrhizin were analyzed by using Gene Ontology (GO) tool, and the action pathway of its target proteins was analyzed by using enrichment method. Text mining results showed that the related diseases of glycyrrhizin included chronic hepatitis C, chronic hepatitis, hepatitis, HIV virus, liver cancer and so on. Gene ontology analysis indicated that glycyrrhizin played a role mainly through modification of proteins and chromatin. The signaling pathway enrichment results showed that the main action proteins of glycyrrhizin were related to MAPK signaling pathway, toll-like receptor signaling pathway, neurotrophic factor signaling pathway, cancer and apoptosis pathways. So we can conclude that glycyrrhizin may exert its biological functions primarily by regulating multiple pathways such as MAPK signaling pathway and Toll-like receptors signaling pathway. The pharmacological action of a drug can be rapidly and comprehensively analyzed by the ways of systems pharmacology.
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Ácido Glicirrízico/farmacologia , Mapas de Interação de Proteínas , Transdução de Sinais/efeitos dos fármacos , Mineração de Dados , Ontologia Genética , Humanos , ProteínasRESUMO
OBJECTIVE: To explore the effect of combination therapy of tetramethylpyrazine (TMP) with methotrexate (MTX) on collagen induced arthritis (CIA) rats. METHODS: Totally 55 male SD rats were stratified by body weight. Nine of them were randomly recruited as the normal control group. The rest 46 were immunized with type II bovine collagen (C II) for establishing rheumatoid arthritis (RA) model. Forty successfully modeled rats were randomly divided into 4 groups according to swollen toe degree, i.e., the CIA group, the TMP group, the MTX group, and the TMP plus MTX group, 10 in each group. Rats in the MTX group were administered with MTX (1. 2 mg/kg) , once per week for 4 continuous weeks. Those in the TMP group were administered with 40 mg/kg TMP, once per day for 10 continuous days, and then discontinued for 7 successive days, and continued for another 10 successive days. Rats in the TMP plus MTX group were administered with a mixture of equal dose MTX and TMP, and when MTX was discontinue, TMP was administered according to the way in the TMP group. Equal volume of saline solution was given to rats in the normal control group and the CIA group. Clinical parameters including ankle width (mediolateral diameter) and hindpaw swelling were measured at day 0, 4, 11, 18, and 26 after treatment. Rats were sacrificed 28 days after treatment, their knee joints and ankle joints were collected for pathological analyses. Serum levels of IL-1ß, IL-6, and IL-17A were detected by ELISA. Changes of fibrinogen (FIB) and platelet aggregation rate (PAg) were detected. RESULTS: Compared with the normal control group, the ankle width and hindpaw swelling increased significantly (P < 0.01), contents of FIB and PAg increased obviously (P < 0.05, P < 0.01), serum levels of IL-1ß, IL-6, and IL-17 increased remarkably (P <0. 01) in the CIA group. Obvious cell proliferation, inflammatory cell infiltration, hyperemia and edema of synovial tissues could be seen. Pannus formed and immerged in cartilages, resulting in necrosis. Compared with the model group, changes of ankle width and hindpaw swelling were all alleviated in each medicated group (P <0. 05, P <0. 01). Of them, the effect was superior in the MTX group to that of the TMP group and the MTX plus TMP group (P < 0.05, P < 0.01). Contents of FIB, serum levels of IL-1ß and IL-6 decreased significantly in the MTX group (P < 0.05). Contents of FIB, serum levels of IL-1ß and IL-6 decreased significantly in the TMP group and the MTX plus TMP group (P < 0.05). Besides, serum levels of FIB and IL-6 were obviously lower in the MTX plus TMP group than in the TMP group and the MTX group (P < 0.01). Levels of PAg and IL-17A were more significantly lowered in the TMP group than in the MTX plus TMP group and the MTX group. Pathological changes could be alleviated in each medicated group, with the optimal effect obtained in the MTX plus TMP group. CONCLUSION: Combination of TMP with MTX could significantly ameliorate inflammatory reactions and FIB contents of CIA rats.
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Quimioterapia Combinada , Medicamentos de Ervas Chinesas/uso terapêutico , Metotrexato/uso terapêutico , Pirazinas/uso terapêutico , Animais , Artrite Experimental , Artrite Reumatoide , Bovinos , Colágeno Tipo II , Hemorreologia , Interleucina-17 , Interleucina-1beta , Interleucina-6 , Masculino , Ratos , Ratos Sprague-Dawley , Membrana SinovialRESUMO
Controlled clinical trials of integrative therapies available to patients with rheumatoid arthritis (RA) improved dramatically in the past 20 years, largely because of the growing need and the methodologies improvement. Tripterygium wilfordii Hook. F., a typical example of popular use herb, has been extensively studied in trials. However, clear and convincing evidence of integrative therapy, effectiveness and safety, remains insufficient to make decision. Many research efforts are hampered by standing problems with 'syndrome' recruitment failure. In addition, the outcome multiplicity induces the findings inefficiency to generalize to RA patients at large. Development of validated syndrome outcomes and methodologies has also been critical. Current efforts to enhance the understanding of integrative treatment options for patients with RA include the development of drug-specific rather than disease-specific strategies, studies in predictive biomarkers, and development of peer-review trial protocol for regular clinical trials.
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Artrite Reumatoide/tratamento farmacológico , Ensaios Clínicos como Assunto , Medicina Integrativa , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Humanos , Tripterygium/químicaRESUMO
AIM: Guizhi-shaoyao-zhimu decoction (GSZ), a traditional Chinese medicine (TCM) herbal formula, has been shown effective in the treatment of diabetic peripheral neuropathy (DPN). In this study, network analysis was performed to decipher the molecular mechanisms of GSZ in the treatment of DPN. METHODS: The chemical components of the 3 herbs forming GSZ, ie, Ramulus Cinnamomi (Guizhi), Paeonia lactiflora (Shaoyao) and Rhizoma Anemarrhenae (Zhimu), were searched in Chinese medicine dictionaries, and their target proteins were identified in PubChem. DPN genes were searched in PubMed gene databases. Ingenuity Pathway Analysis (IPA) was used to build the GSZ pharmacological network and DPN molecular network. The canonical pathways between the two networks were compared to decipher the molecular mechanisms of GSZ in the treatment of DPN. RESULTS: Sixty-one protein targets for Guizhi, 31 targets for Shaoyao, 47 targets for Zhimu, as well as 23 genes related to DPN were identified and uploaded to IPA. The primary functions of the DPN molecular network were inflammatory response, metabolic disease, cellular assembly and organization. As far as the pharmacological network functions were concerned, Guizhi target proteins were involved in neurological disease, inflammatory disease, cellular growth and proliferation, cell signaling, molecular transport, and nucleic acid metabolism, Shaoyao target proteins were related to neurological disease, inflammatory disease, and Zhimu target proteins focused on cell death and survival, cellular movement, immune cell trafficking, DNA replication, recombination and repair, and cell cycle. In the three-herb combination GSZ, several new network functions were revealed, including the inflammatory response, gene expression, connective tissue development and function, endocrine system disorders, and metabolic disease. The canonical pathway comparison showed that Shaoyao focused on IL-12 signaling and production in macrophages, and Zhimu focused on TNFR2 signaling, death receptor signaling, ILK signaling, IL-17A in gastric cells, IL-6 signaling, IL-8 signaling, the role of JAK1, JAK2, and TYK2 in interferon signaling, IL-9 signaling, HMGB1 signaling, NO production and ROS production in macrophages, whereas GSZ focused aryl hydrocarbon receptor signaling and apoptosis signaling in addition to those pathways induced by Guizhi, Shaoyao and Zhimu. CONCLUSION: Although each single herb can affect some DPN-related functions and pathways, GSZ exerts more effects on DPN-related functions and pathways. The effects of GSZ on aryl hydrocarbon receptor signaling and apoptosis signaling pathways may be the key components of its total molecular mechanisms.
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Neuropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Genômica/métodos , Medicina Tradicional Chinesa/métodos , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Biologia de Sistemas/métodos , Animais , Análise por Conglomerados , Mineração de Dados , Bases de Dados Genéticas , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/genética , Neuropatias Diabéticas/metabolismo , Combinação de Medicamentos , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/metabolismo , Mapas de Interação de Proteínas , Transdução de Sinais/efeitos dos fármacos , Integração de Sistemas , Resultado do TratamentoRESUMO
Fine particulate matter (PM2.5) is a significant environmental pollutant responsible for a number of human diseases. Ginsenoside Rg1 (Rg1) is likely to have the potential to relieve PM2.5induced cell injury. The present study is designed to preliminarily observe the harmful effect of PM2.5 and the protective effect of Rg1 against PM2.5 on human A549 lung epithelial cells in vitro. The cytotoxic effects of the PM2.5 or Rg1 on A549 cells were measured by means of cell viability, and then exposure concentration of PM2.5 and pretreatment concentration of Rg1 used in the following assays were established. The A549 cells were pretreated with Rg1 for 1 h and then exposed to PM2.5 for 24 h. The levels of lactate dehydrogenase (LDH) in the cell culture supernatant and malondialdehyde (MDA) within the cells were assayed. The present results revealed that 2001,200 µg/ml of PM2.5 decreased the viability of A549 cells significantly in a concentrationdependent manner; however, 50400 µg/ml of Rg1 had no significant effect. Pretreatment with 100, 200 or 400 µg/ml Rg1 significantly diminished the 200 µg/ml PM2.5induced A549 cell viability and decreased LDH leakage and MDA generation in a concentrationdependent manner. These results indicated that PM2.5 induced cell injury and Rg1, antagonized PM2.5induced cell injury to a certain extent.
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Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Ginsenosídeos/farmacologia , Material Particulado/toxicidade , Linhagem Celular Tumoral , Fármacos do Sistema Nervoso Central/farmacologia , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Malondialdeído/metabolismoRESUMO
One of effective measures for controlling toxic reactions is to use toxic herbs according to corresponding indication syndrome. It is important to develop toxicity theory of Chinese medicine in a sound and international way using modern language to elucidate its scientific connotation. We expect to explain scientific connotation of controlling toxic reaction while toxic herbs are used to the indication syndrome by using holistic research ideas and methods capable of reflecting governing exterior to infer interior, establish appropriate corresponding syndrome animal models by cutting into dose-effect/toxicity of toxic Chinese herbs, construct and analyze multi-layer molecular network using theories and technologies of metabonomics, network biology, and bioinformatics.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Medicamentos de Ervas Chinesas/toxicidade , Medicina Tradicional Chinesa/métodosRESUMO
OBJECTIVE: To observe the effects of Radix Glycyrrhizae polysaccharide on regulatory T cells (Treg) in spleen and lymphocyte transformation ratio in tumor-bearing mice so as to explore the mechanisms of its immunoregulatory function. METHODS: Fifty BALB/c mice were randomly divided into normal group, untreated group, cyclophosphamide group, Radix Glycyrrhizae polysaccharide group and Radix Glycyrrhizae polysaccharide plus cyclophosphamide group. Except normal group, mice were subcutaneously implanted H22 tumor cells in the right axillary region. After 24 h, mice in normal and untreated group were subcutaneously injected with physiological saline, while mice in the cyclophosphamide group were intraperitoneally injected with cyclophosphamide and mice in Radix Glycyrrhizae polysaccharide group were subcutaneously injected with polysaccharide. Fourteen days later, Treg cells of spleen were detected by flow cytometry and lymphocyte transformation ratio was detected by methyl thiazolyl tetrazolium method. RESULTS: The proportion of Treg cells was significantly higher in the untreated group than in the normal group, and was lower in the Radix Glycyrrhizae polysaccharide group than in the untreated group (P < p0.01). Lymphocyte transformation ratio in the Radix Glycyrrhizae polysaccharide group was higher than that in the cyclophosphamide group. There was no interaction between Radix Glycyrrhizae polysaccharide and cyclophosphamide. CONCLUSION: Radix Glycyrrhizae polysaccharide can regulate the cellular immunity disorders of tumor-bearing mice by decreasing proportion of Treg cells and increasing spleen lymphocyte transformation ratio.