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1.
J Fluoresc ; 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37870733

RESUMO

In this paper, a ratiometric fluorescence biosensor was introduced for alkaline phosphatase (ALP) detection based on 2-aminopurine (2-Amp) and thioflavin T (ThT)-G-quadruplex system. We designed a special DNA (5'-AGGGTTAGGGTTAGGGTTAGGGAAA/i2-Amp/AAAA-PO4-3', AP) modified with a phosphate moiety at the 3'-end, G-quadruplex at the 5'-end, and a fluorophore (2-Amp) in the middle. In the absence of ALP, the G-rich AP strand could be prone to fold into G-quadruplex structures in the presence of K+. Then, ThT combined with G-quandruplex, resulting in the enhancement of fluorescence emission peak at 485 nm. However, ALP-mediated hydrolysis of the 3'-phosphoryl end promoted the cleavage of AP by the exonuclease I (Exo I), releasing 2-Amp which displayed a strong fluorescence emission peak at 365 nm. Moreover, the quantitative fluorescence model (QFM) was derived for the analysis of the fluorescence measurements obtained by the proposed ratiometric fluorescent biosensor. With the aid of the advanced model, the proposed ratiometric fluorescent biosensor possessed satisfactory results for the detection of ALP in the human serum samples, with accuracy comparable to that of the reference method-the commercial ALP assay kit. Under the optimized experimental conditions, this method exhibited good selectivity and higher sensitivity, and the detection limit was found to be as low as 0.017 U/L. Therefore, it is reasonable to expect that the method had a great potential to detect ALP quantitatively in clinical diagnosis.

2.
Phytochemistry ; 214: 113796, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37499849

RESUMO

- Seven previously undescribed ent-eudesmane sesquiterpenoids (1-7), as well as seven known analogs (8-14), were isolated from the Chinese liverwort Chiloscyphus polyanthus var. rivularis. Their structures were established based on comprehensive spectroscopy analysis, electronic circular dichroism calculations, as well as biosynthetic considerations. The cytotoxicity against HepG2 (Human hepatocellular carcinomas) cancer cell line, and antifungal activity against Candida albicans SC5314 of all isolated ent-eudesmane sesquiterpenoids were preliminarily tested, results showed that the tested compounds did not display obvious cytotoxicity and antifungal activities under the tested concentration.


Assuntos
Antifúngicos , Antineoplásicos , Hepatófitas , Sesquiterpenos de Eudesmano , Sesquiterpenos , Antifúngicos/farmacologia , Antifúngicos/química , China , Hepatófitas/química , Estrutura Molecular , Sesquiterpenos/química , Sesquiterpenos de Eudesmano/farmacologia , Sesquiterpenos de Eudesmano/química , Células Hep G2/efeitos dos fármacos , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia
3.
Adv Ther ; 40(9): 3784-3803, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37351811

RESUMO

INTRODUCTION: The efficacy of sugammadex on postoperative pulmonary complications (PPCs) in susceptible patients, compared with neostigmine, remains indeterminate. The Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) Group Investigators proposed a risk index for the early identification of susceptible patients, with excellent externally validated discrimination ability. Meta-analytical techniques were applied to evaluate the efficacy of sugammadex on PPCs in patients with ARISCAT-defined risk factors. METHODS: The study is registered on PROSPERO, number CRD42021261156. We searched PubMed, Scopus, Embase, Cochrane library, GreyNet, and OpenGrey for eligible randomized controlled trials (RCTs) without restricting the language or year of publication. RESULTS: Twelve RCTs consisting of 1182 patients susceptible to PPCs were included. A robust reduction was observed on the incidence of PPCs in susceptible patients who received sugammadex [RR 0.66; 95% CI (0.54, 0.80), p < 0.01], with a low level of between-study heterogeneity (I2 = 45.98%; H2 = 1.85). Similar protective effects were also proved in avoiding residual neuromuscular block (NMB) [RR 0.25; 95% CI (0.11, 0.56); p < 0.01], atelectasis [RR 0.74; 95% CI (0.59, 0.95); p = 0.02], pneumonia [RR 0.49; 95% CI (0.28, 0.88); p = 0.02], and respiratory failure [RR 0.61; 95% CI (0.39, 0.96); p = 0.03]. No difference was observed regarding adverse events [RR 0.85; 95% CI (0.72, 1.01); p = 0.06]. CONCLUSION: Low to moderate quality of evidence demonstrated the edge of sugammadex over neostigmine for NMB reversal in reducing the likelihood of PPCs and residual NMB in patients with ARISCAT-defined risk factors. Clinicians may reassess the type of reversal agent when treating patients susceptible to PPCs.


Assuntos
Bloqueio Neuromuscular , Atelectasia Pulmonar , Humanos , Sugammadex/uso terapêutico , Incidência , Neostigmina/uso terapêutico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Bloqueio Neuromuscular/efeitos adversos
4.
Phytochemistry ; 212: 113702, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37149119

RESUMO

Three unprecedented ent-labdane and pallavicinin based dimers pallamins A-C formed via [4 + 2] Diels-Alder cycloaddition, together with eight biosynthetically related monomers were isolated from Pallavicinia ambigua. Their structures were determined by the extensive analysis of HRESIMS and NMR spectra. The absolute configurations of the labdane dimers were determined by single crystal X-ray diffraction of the homologous labdane units, and 13C NMR and ECD calculations. Moreover, a preliminary evaluation of the anti-inflammatory activities of the isolated compounds was performed using the zebrafish model. Three of the monomers demonstrated significant anti-inflammatory activity.


Assuntos
Diterpenos , Hepatófitas , Animais , Diterpenos/farmacologia , Diterpenos/química , Hepatófitas/química , Estrutura Molecular , Peixe-Zebra , China
5.
Infect Genet Evol ; 111: 105431, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37015318

RESUMO

BACKGROUND: Emergence and predominance of hepatitis B virus (HBV) variants carrying S gene mutations frequently occur in HBV-infected individuals. Here, coexistent serum anti-HBsAg antibody (HBsAb) and HBV surface antigen (HBsAg) were detected in a chronic HBV patient. The patient's HBsAg proteins possessed amino acid substitutions sK122R and sV96A. We reported this case and conducted relevant studies to investigate differences in expression levels and antibody neutralization of HBsAg proteins bearing sK122R and sV96A amino acid substitutions to explore causes of antigen-antibody coexistence in a chronic hepatitis B patient. STUDY DESIGN: We first sequenced the S gene from HBV present within the patient's serum. Based on the S gene sequence, we cloned wild-type and mutated S gene sequences via site-directed mutagenesis to construct expression plasmids pJW4303-WT (wild-type), pJW4303-sV96A, pJW4303-sK122R, and pJW4303-sV96A-sK122R. Plasmids were transfected into HEK 293 T cells then culture supernatants and cells were collected. Collected cells and supernatants were next subjected to a series of quantitative and functional tests to assess expression and neutralization characteristics of wild-type and mutant HBsAg proteins. RESULTS: Based on quantification of HBsAg expression in cells transfected with the four plasmids, HBsAg-sK122R-sV96A was more intracellularly retained and less secreted than HBsAg-sV96A single-mutant protein and WT. Neutralization ability of serum from chronic HBV patient against culture supernatants containing recombinant HBsAg proteins were ranked from highest to lowest as HBsAg-sV96A, HBsAg-sV96A-sK122R, and HBsAg-sK122R. However, no significant differences of neutralization efficiency by high-potency antibodies from HBV-vaccinees against these three mutant proteins were observed. CONCLUSIONS: The levels of HBsAg proteins with amino acid substitutions sV96A-sK122R were greatly reduced in culture supernatants but were apparently increased in the intracellular fraction. This may account for the higher levels of HBV replication in patients. HBsAg neutralization by HBsAb in this patient may have been compromised by the HBsAg sK122R amino acid substitution, suggesting that antibodies produced by the patient had lost their HBV-neutralizing effect.


Assuntos
Hepatite B Crônica , Hepatite B , Humanos , Vírus da Hepatite B/genética , Antígenos de Superfície da Hepatite B , Antígenos de Superfície , Formação de Anticorpos , Células HEK293 , Mutação , Anticorpos Anti-Hepatite B
6.
J Fungi (Basel) ; 9(3)2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36983493

RESUMO

Plant-parasitic nematodes cause severe economic losses to agriculture. As important biocontrol agents, nematophagous fungi evolved the ability to obtain nitrogen sources from nematodes. However, the impact of nitrogen sources on the growth and development of these fungi is largely unknown. In this study, we aimed to better understand how nitrogen sources could influence vegetative growth and conidiation through epigenetic regulation in the nematophagous fungus, Purpureocillium lavendulum. Through nutrition screening, we found a phenomenon of the fungus, limited colony extension with a large amount of conidia production when cultured on PDA media, can be altered by adding ammonia nitrate. Characterized by site-directed mutagenesis, the histone H3K14 acetylation was found to be involved in the alternation. Furthermore, the acetyltransferase PlGCN5 was responsible for H3K14 acetylation. Knockout of Plgcn5 severely diminished conidiation in P. lavendulum. Chip-seq showed that H3K14ac distributed in conidiation regulating genes, and genes in the MAPK pathway which may be the downstream targets in the regulation. These findings suggest that histone modification and nitrogen sources coordinated lifestyle regulation in P. lavendulum, providing new insight into the mechanism of growth regulation by nutritional signals for the carnivorous fungus.

7.
Front Cardiovasc Med ; 9: 1042573, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36531715

RESUMO

Aims: Several models have been developed to predict the risk of atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA). However, these models are of poor quality from the start. We, therefore, aimed to develop and validate a predictive model for post-operative recurrence of AF. Materials and methods: In a study including 433 patients undergoing the first circumferential pulmonary vein isolation (CPVI) procedure, independent predictors of AF recurrence were retrospectively identified. Using the Cox regression of designated variables, a risk model was developed in a random sample of 70% of the patients (development cohort) and validated in the remaining (validation cohort) 30%. The accuracy and discriminative power of the predictive models were evaluated in both cohorts. Results: During the established 12 months follow-up, 134 patients (31%) recurred. Six variables were identified in the model including age, coronary artery disease (CAD), heart failure (HF), hypertension, transient ischemic attack (TIA) or cerebrovascular accident (CVA), and left atrial diameter (LAD). The model showed good discriminative power in the development cohort, with an AUC of 0.77 (95% confidence interval [CI], 0.69-0.86). Furthermore, the model shows good agreement between actual and predicted probabilities in the calibration curve. The above results were confirmed in the validation cohort. Meanwhile, decision curve analysis (DCA) for this model also demonstrates the advantages of clinical application. Conclusion: A simple risk model to predict AF recurrence after ablation was developed and validated, showing good discriminative power and calibration.

8.
Chem Biodivers ; 19(9): e202200559, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35843891

RESUMO

An unprecedented 4,9-seco-oplopanane (1), two undescribed drimane epimers (2 and 3), and five known drimane sesquiterpenoids (4-8) were isolated from the Chinese liverwort Lejeunea flava (Sw.) Nees. The structures of the new sesquiterpenoids were determined using nuclear magnetic resonance spectroscopy, electronic circular dichroism calculations, and single-crystal X-ray diffraction measurements. The inhibitory capacity of the new compounds against nitric oxide production in lipopolysaccharide-induced RAW 264.7 murine macrophages, along with the cytotoxicity of the new compounds against A549 and HepG-2 human cancer cell lines, were discussed.


Assuntos
Anemone , Hepatófitas , Sesquiterpenos , Animais , China , Hepatófitas/química , Humanos , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico , Sesquiterpenos Policíclicos , Sesquiterpenos/química , Sesquiterpenos/farmacologia
9.
World J Clin Cases ; 9(28): 8492-8497, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34754858

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) may be caused by hepatitis B virus (HBV) infection. Post-infection recovery-associated changes of HBV indicators include decreased hepatitis B surface antigen (HBsAg) level and increased anti-HBsAg antibody titer. Testing to detect HBV DNA is conducted rarely but could detect latent HBV infection persisting after acute infection and prompt administration of treatments to clear HBV and prevent subsequent HBV-induced HCC development. Here, we present an HCC case with an extremely high anti-HBsAg antibody titer and latent HBV infection. CASE SUMMARY: A 57-year-old male patient with abdominal pain who was diagnosed with primary HCC presented with an extremely high level (over 2000 ng/mL) of serum alpha-fetoprotein. Abdominal B-ultrasonography and computed tomography scan results indicated focal liver lesion and mild splenomegaly. Assessments of serological markers revealed a high titer of antibodies against hepatitis B core antigen (anti-HBcAg antibodies), an extremely high titer (1000 mIU/mL) of hepatitis B surface antibodies (anti-HBsAg antibodies, anti-HBs) and absence of detectible HBsAg. Medical records indicated that the patient had reported no history of HBV vaccination, infection or hepatitis. Therefore, to rule out latent HBV infection in this patient, a serum sample was collected then tested to detect HBV DNA, yielding a positive result. Based on the aforementioned information, the final diagnosis was HCC associated with hepatitis B in a compensated stage of liver dysfunction and the patient was hospitalized for surgical treatment. CONCLUSION: A rare HCC case with high serum anti-HBsAg antibody titer and detectable HBV DNA resulted from untreated latent HBV infection.

10.
Angew Chem Int Ed Engl ; 60(28): 15286-15290, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33876516

RESUMO

An enantioselective synthetic approach for preparing manginoids and guignardones, two types of biogenetically related meroterpenoids, is reported. This bioinspired and divergent synthesis employs an oxidative 1,3-dicarbonyl radical-initiated cyclization and cyclodehydration of the common precursor to forge the central ring of the manginoids and guignardones, respectively, at a late stage. Key synthetic steps include silica-gel-promoted semipinacol rearrangement to form the 6-oxabicyclo[3.2.1]octane skeleton and the Suzuki-Miyaura reaction of vinyl bromide to achieve fragment coupling. This synthesis protocol enables the asymmetric syntheses of four fungal meroterpenoids from commercially available materials.

11.
mSphere ; 5(5)2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33115838

RESUMO

The nematophagous fungus Purpureocillium lavendulum is a natural enemy of plant-parasitic nematodes, which cause severe economic losses in agriculture worldwide. The production of asexual spores (conidia) in P. lavendulum is crucial for its biocontrol activity against nematodes. In this study, we characterized the core regulatory genes involved in conidiation of P. lavendulum at the molecular level. The central regulatory pathway is composed of three genes, P. lavendulumbrlA (PlbrlA), PlabaA, and PlwetA, which regulate the early, middle, and late stages of asexual development, respectively. The deletion of PlbrlA completely inhibited conidiation, with only conidiophore stalks produced. PlAbaA determines the differentiation of conidia from phialides. The deletion of PlwetA affected many phenotypes related to conidial maturation, including abscission of conidia from conidium strings, thickening of the cell wall layers, vacuole generation inside the cytoplasm, production of trehalose, tolerance to heat shock, etc. Comparative analyses showed that the upstream regulators of the core regulatory pathway of conidiation, especially the "fluffy" genes, were different from those in Aspergillus Besides their roles in conidiation, the central regulators also influence the production of secondary metabolites, such as the leucinostatins, in P. lavendulum Our study revealed a set of essential genes controlling conidiation in P. lavendulum and provided a framework for further molecular genetic studies on fungus-nematode interactions and for the biocontrol of plant-parasitic nematodes.IMPORTANCE Plant-parasitic nematodes cause serious damage to crops throughout the world. Purpureocillium lavendulum is a nematophagous fungus which is a natural enemy of nematodes and a potential biocontrol agent against plant-parasitic nematodes. The conidia play an important role during infection of nematodes. In this study, we identified and characterized genes involved in regulating asexual development of P. lavendulum We found that these genes not only regulate conidiation but also influence secondary-metabolite production. This work provides a basis for future studies of fungus-nematode interactions and nematode biocontrol.


Assuntos
Proteínas Fúngicas/genética , Genes Reguladores , Hypocreales/crescimento & desenvolvimento , Hypocreales/genética , Regulação Fúngica da Expressão Gênica , Reprodução Assexuada , Esporos Fúngicos/genética , Esporos Fúngicos/crescimento & desenvolvimento
12.
BMC Gastroenterol ; 20(1): 189, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32539842

RESUMO

BACKGROUND: Endoscopic biliary stenting by endoscopic retrograde cholangiopancreatography (ERCP) is the most common form of palliation for malignant hilar obstruction. However, ERCP in such cases is associated with a risk of cholangitis. The incidence of post-ERCP cholangitis is particularly high in Bismuth type IV hilar obstruction, and this risk is further increased when the contrast injected for cholangiography is not drained. The present study aims to compare the incidence of cholangitis associated with the use of a contrast agent, air and CO2 for cholangiography in type IV hilar biliary lesions. METHODS: The clinical data of consecutive 70 patients with type IV hilar obstruction, who underwent ERCP from October 2013 to November 2017, were retrospectively analyzed. These patients were divided into three groups based on the agent used for cholangiography: group A, contrast (n = 22); group B, air (n = 18); group C, CO2 (n = 30). These three methods of cholangiography were chronologically separated. Prior to the ERCP, MRCP was obtained from all patients to guide the endoscopic intervention. RESULTS: At baseline, there was no significant difference in terms of the patient's age, gender, symptoms and liver function tests among the three groups (P > 0.05). The complication rates were significantly higher in group A than in groups B and C (63.6% vs. 26.7 and 27.8%, P < 0.05). The incidence of post-ERCP cholangitis was significantly higher in group A (P < 0.05), while the incidence of post-ERCP pancreatitis and bleeding were similar in the three groups. After the ERCP, the mean hospital stay was shorter in groups B and C, when compared to group A (P < 0.05). However, there was no significant difference in the 30-day mortality rate among the three groups (P > 0.05). Furthermore, there was no significant difference between groups B and C in terms of primary end points. CONCLUSION: CO2 or air cholangiography during ERCP for type IV hilar obstruction is associated with reduced risk of post-ERCP cholangitis, when compared to conventional contrast agents.


Assuntos
Dióxido de Carbono/efeitos adversos , Colangiografia/efeitos adversos , Colangite/epidemiologia , Meios de Contraste/efeitos adversos , Pneumorradiografia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Neoplasias dos Ductos Biliares/cirurgia , Colangiografia/métodos , Colangite/etiologia , Feminino , Humanos , Incidência , Tumor de Klatskin/cirurgia , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/métodos , Pneumorradiografia/métodos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento
13.
Microbes Environ ; 35(1)2020.
Artigo em Inglês | MEDLINE | ID: mdl-31969532

RESUMO

The pmoA gene, encoding particulate methane monooxygenase in methanotrophs, and nirS and nirK genes, encoding bacterial nitrite reductases, were examined in the root and rhizosphere sediment of three common emergent macrophytes (Phragmites australis, Typha angustifolia, and Scirpus triqueter) and unvegetated sediment from eutrophic Wuliangsuhai Lake in China. Sequencing analyses indicated that 334 out of 351 cloned pmoA sequences were phylogenetically the most closely related to type I methanotrophs (Gammaproteobacteria), and Methylomonas denitrificans-like organisms accounted for 44.4% of the total community. In addition, 244 out of 250 cloned nirS gene sequences belonged to type I methanotrophs, and 31.2% of nirS genes were the most closely related to paddy rice soil clone SP-2-12 in Methylomonas of the total community. Three genera of type I methanotrophs, Methylomonas, Methylobacter, and Methylovulum, were common in both pmoA and nirS clone libraries in each sample. A quantitative PCR (qPCR) analysis demonstrated that the copy numbers of the nirS and nirK genes were significantly higher in rhizosphere sediments than in unvegetated sediments in P. australis and T. angustifolia plants. In the same sample, the nirS gene copy number was significantly higher than that of nirK. Furthermore, type I methanotrophs were localized in the root tissues according to catalyzed reporter deposition-fluorescence in situ hybridization (CARD-FISH). Thus, nirS-carrying type I methanotrophs were enriched in macrophyte root and rhizosphere sediment and are expected to play important roles in carbon/nitrogen cycles in a eutrophic wetland.


Assuntos
Eutrofização , Gammaproteobacteria/genética , Genes Bacterianos/genética , Magnoliopsida/microbiologia , Microbiologia do Solo , Áreas Alagadas , Proteínas de Bactérias/genética , China , Gammaproteobacteria/classificação , Gammaproteobacteria/metabolismo , Dosagem de Genes , Lagos/microbiologia , Metano/metabolismo , Nitrito Redutases/genética , Oxigenases/genética , Raízes de Plantas/microbiologia , Rizosfera
14.
Fungal Biol ; 123(4): 274-282, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30928036

RESUMO

The fungus Purpureocillium lavendulum (formally Paecilomyces lilacinus) is a natural enemy of insects and plant-parasitic nematodes, and has been used as an important bio-control agent against agricultural pests all over the world. In order to understand the genetic mechanisms governing its biocontrol efficiency and other biological processes, an effective gene disruption system is needed. Here we report the development of an efficient system which integrates selective markers that differ from Purpureocillium lilacinum, a one-step construction method for gene knockout plasmids, and a ku80 knockout strain for efficient homologous recombination. With this system, we effectively disrupted the transcription factors in the central regulation pathway of sporulation and a serine protease which were contributed to nematode infection, demonstrating this system as an efficient gene disrupting system for further characterization of genes involved in the development and pathogenesis of this fungus.


Assuntos
Técnicas de Inativação de Genes/métodos , Genética Microbiana/métodos , Hypocreales/genética , Biologia Molecular/métodos , Vetores Genéticos , Recombinação Homóloga , Plasmídeos , Seleção Genética
15.
Blood Cancer J ; 8(11): 110, 2018 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-30420593

RESUMO

Peripheral T cell lymphomas (PTCL) is a heterogenous group of non-Hodgkin lymphoma and many patients remain refractory to the frontline therapy. Identifying new prognostic markers and treatment is an unmet need in PTCL. We analyzed phospho-STAT3 (pSTAT3) expression in a cohort of 169 PTCL tumors and show overall 38% positivity with varied distribution among PTCL subtypes with 27% (16/59) in PTCL-NOS; 29% (11/38) in AITL, 57% (13/28) in ALK-negative ALCL, and 93% in ALK-pos ALCL (14/15), respectively. Correlative analysis indicated an adverse correlation between pSTAT3 and overall survival (OS). PTPN6, a tyrosine phosphatase and potential negative regulator of STAT3 activity, was suppressed in 62% of PTCL-NOS, 42% of AITL, 60% ALK-neg ALCL, and 86% of ALK-pos ALCL. Loss of PTPN6 combined with pSTAT3 positivity predicted an infwere considered significantferior OS in PTCL cases. In vitro treatment of TCL lines with azacytidine (aza), a DNA methyltransferase inhibitor (DNMTi), restored PTPN6 expression and decreased pSTAT3. Combining DNMTi with JAK3 inhibitor resulted in synergistic antitumor activity in SUDHL1 cell line. Overall, our results suggest that PTPN6 and activated STAT3 can be developed as prognostic markers, and the combination of DNMTi and JAK3 inhibitors as a novel treatment for patients with PTCL subtypes.


Assuntos
Linfoma de Células T Periférico/metabolismo , Linfoma de Células T Periférico/mortalidade , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Fator de Transcrição STAT3/metabolismo , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Janus Quinases/metabolismo , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/genética , Terapia de Alvo Molecular , Fosforilação , Prognóstico , Proteína Tirosina Fosfatase não Receptora Tipo 6/genética , Fator de Transcrição STAT3/genética , Resultado do Tratamento
16.
Org Lett ; 20(20): 6550-6553, 2018 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-30289265

RESUMO

Two novel ent-aromadendrane derivatives, plagiochianin A (1), possessing an unprecedented 2,3:6,7-di- seco-6,8-cyclo-aromadendrane carbon scaffold conjugated with three cyclic acetals, and plagiochianin B (2), an exceptional pyridine type aromadendrane alkaloid, were isolated from the Chinese liverwort Plagiochila duthiana. Their structures were established by comprehensive spectroscopic analysis coupled with single-crystal X-ray diffraction and electronic circular dichroism calculations. A plausible biogenetic pathway of these two compounds is presented, and their acetylcholinesterase inhibitory activities are preliminarily tested using TLC-bioautographic assays.

17.
Sci Rep ; 8(1): 5645, 2018 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-29618826

RESUMO

Multiple components of traditional Chinese medicine (TCM) formulae determine their treatment targets for multiple diseases as opposed to a particular disease. However, discovering the unexplored therapeutic potential of a TCM formula remains challenging and costly. Inspired by the drug repositioning methodology, we propose an integrated strategy to feasibly identify new therapeutic uses for a formula composed of six herbs, Liuweiwuling. First, we developed a comprehensive systems approach to enrich drug compound-liver disease networks to analyse the major predicted diseases of Liuweiwuling and discover its potential effect on liver failure. The underlying mechanisms were subsequently predicted to mainly attribute to a blockade of hepatocyte apoptosis via a synergistic combination of multiple effects. Next, a classical pharmacology experiment was designed to validate the effects of Liuweiwuling on different models of fulminant liver failure induced by D-galactosamine/lipopolysaccharide (GalN/LPS) or thioacetamide (TAA). The results indicated that pretreatment with Liuweiwuling restored liver function and reduced lethality induced by GalN/LPS or TAA in a dose-dependent manner, which was partially attributable to the abrogation of hepatocyte apoptosis by multiple synergistic effects. In summary, the integrated strategy discussed in this paper may provide a new approach for the more efficient discovery of new therapeutic uses for TCM formulae.


Assuntos
Apoptose/efeitos dos fármacos , Bases de Dados Factuais , Medicamentos de Ervas Chinesas/farmacologia , Redes Reguladoras de Genes , Falência Hepática/classificação , Falência Hepática/tratamento farmacológico , Biologia de Sistemas/métodos , Animais , Descoberta de Drogas , Galactosamina/toxicidade , Lipopolissacarídeos/toxicidade , Falência Hepática/induzido quimicamente , Falência Hepática/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transdução de Sinais
18.
J Med Chem ; 61(4): 1609-1621, 2018 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-29406740

RESUMO

The plant metabolite 3,4,5-tri-O-galloylquinic acid methyl ester (TGAME, compound 6) was synthesized, and its potential effect on calcium oxalate monohydrate (COM) crystal binding to the surface of Madin-Darby canine kidney cells type I (MDCKI) and crystal growth in a Drosophila melanogaster Malpighian tubule (MT) model were investigated. Membrane, cytosolic, and total annexin A1 (AxA1), α-enolase, and heat shock protein 90 (HSP90) amounts were examined by Western blot analysis after subcellular fractionation, then confirmed by immunofluorescence staining of cultured cells. Pretreatment of MDCKI cells with TGAME for up to 6 h significantly diminished COM crystal binding in a concentration-dependent manner. TGAME significantly inhibited AxA1 surface expression by immunofluorescence microscopy, whereas intracellular AxA1 increased. Western blot analysis confirmed AxA1 expression changes in the membrane and cytosolic fractions of compound-treated cells, whereas whole cell AxA1 remained unchanged. TGAME also significantly decreased the size, number, and growth of calcium oxalate (CaOx) crystals induced in a Drosophila melanogaster MT model and possessed a potent antioxidant activity in a DPPH assay.


Assuntos
Anexina A1/efeitos dos fármacos , Oxalato de Cálcio/química , Adesão Celular/efeitos dos fármacos , Ácido Gálico/análogos & derivados , Ácido Quínico/análogos & derivados , Animais , Anexina A1/metabolismo , Antioxidantes , Linhagem Celular , Cristalização , Cães , Drosophila melanogaster , Ácido Gálico/síntese química , Ácido Gálico/química , Ácido Gálico/farmacologia , Células Madin Darby de Rim Canino/efeitos dos fármacos , Células Madin Darby de Rim Canino/metabolismo , Túbulos de Malpighi/química , Ácido Quínico/síntese química , Ácido Quínico/química , Ácido Quínico/farmacologia , Frações Subcelulares/química , Frações Subcelulares/metabolismo
19.
J Sep Sci ; 39(11): 2172-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27062107

RESUMO

High-speed countercurrent chromatography, combined with macroporous resin chromatography were applied to the separation and purification of flavans from Ixeris chinensis. Four flavans, namely, 5-methoxy-7,4'-dihydroxyflavan-3-ol (1), 5,7-dimethoxy-4'-hydroxyflavan-3-ol (2), 5,7-dimethoxy-4'-hydroxyflavan (3), and 5,7-dimethoxy-8-methyl-4'-hydroxyflavan (4), were obtained from I. chinensis for the first time. Their chemical structural identification was carried out by spectroscopic methods, including 1D and 2D NMR spectroscopy. Amounts of 13.2 mg of compound 1, 6.4 mg of compound 2, 5.8 mg of compound 3, and 14.5 mg of compound 4 were separated from 120 mg 75% ethanol fraction. The purities of 1-4 were 99.1, 99.2, 97.3, and 98.6 %, respectively.


Assuntos
Asteraceae/química , Flavonoides/química , Flavonoides/isolamento & purificação , Distribuição Contracorrente , Espectroscopia de Ressonância Magnética , Porosidade , Resinas Sintéticas/química
20.
Data Brief ; 6: 803-10, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26937451

RESUMO

Fibronectin and collagen type I are abundant extracellular matrix proteins that modulate cell mechanics and they regulate angiogenic sprouting. In this data article, fibronectin- or collagen type I-coated micro-posts were used to examine the traction force, cell spread area and directional contraction of human umbilical vein endothelial cells (HUVECs).

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