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1.
Int J Mol Sci ; 25(10)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38791176

RESUMO

Extensive microbial interactions occur within insect hosts. However, the interactions between the Huanglongbing (HLB) pathogen and endosymbiotic bacteria within the Asian citrus psyllid (ACP, Diaphorina citri Kuwayama) in wild populations remain elusive. Thus, this study aimed to detect the infection rates of HLB in the ACP across five localities in China, with a widespread prevalence in Ruijin (RJ, 58%), Huidong (HD, 28%), and Lingui (LG, 15%) populations. Next, microbial communities of RJ and LG populations collected from citrus were analyzed via 16S rRNA amplicon sequencing. The results revealed a markedly higher microbial diversity in the RJ population compared to the LG population. Moreover, the PCoA analysis identified significant differences in microbial communities between the two populations. Considering that the inter-population differences of Bray-Curtis dissimilarity in the RJ population exceeded those between populations, separate analyses were performed. Our findings indicated an increased abundance of Enterobacteriaceae in individuals infected with HLB in both populations. Random forest analysis also identified Enterobacteriaceae as a crucial indicator of HLB infection. Furthermore, the phylogenetic analysis suggested a potential regulatory role of ASV4017 in Enterobacteriaceae for ACP, suggesting its possible attractant activity. This research contributes to expanding the understanding of microbial communities associated with HLB infection, holding significant implications for HLB prevention and treatment.


Assuntos
Enterobacteriaceae , Hemípteros , Filogenia , Doenças das Plantas , RNA Ribossômico 16S , Animais , Hemípteros/microbiologia , Enterobacteriaceae/genética , Enterobacteriaceae/classificação , Enterobacteriaceae/patogenicidade , RNA Ribossômico 16S/genética , Doenças das Plantas/microbiologia , China/epidemiologia , Citrus/microbiologia , Microbiota
2.
Funct Integr Genomics ; 23(2): 170, 2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-37209314

RESUMO

As a toxic heavy metal, cadmium (Cd) is one of the principal pollutants influencing rice productivity and food security. Despite several studies, the underlying mechanism of Cd response in plants remains largely unclear. Dehydrins are part of the late embryogenesis abundant (LEA) family which protect plants against abiotic stresses. In this study, a Cd-responsive LEA gene, OsDHN2, was functionally characterized. The chromosome localization results indicated that OsDHN2 was located on chromosome 2 of rice. Meanwhile, cis-acting elements, such as MBS (MYB binding site involved in drought-inducibility), ARE (anaerobic induction), and ABRE (abscisic acid), were present in the OsDHN2 promoter region. Expression pattern analysis also showed that OsDHN2 expression was induced in both roots and shoots under Cd stress. Overexpression of OsDHN2 improved Cd tolerance and reduced Cd concentration in yeast. Moreover, increased expression levels of SOD1, CTA1, GSH1, or CTT1 were found in transgenic yeast under Cd stress, suggesting the increased antioxidant enzymatic activities. These results suggested that OsDHN2 is a Cd-responsive gene that has the potential to improve resistance to Cd in rice.


Assuntos
Cádmio , Oryza , Cádmio/toxicidade , Cádmio/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oryza/genética , Oryza/metabolismo , Biologia Computacional , Regulação da Expressão Gênica de Plantas
3.
Plant Cell Environ ; 45(5): 1520-1536, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35150141

RESUMO

Nitrogen (N) is an essential macronutrient for crop growth and yield. Improving the N use efficiency (NUE) of crops is important to agriculture. However, the molecular mechanisms underlying NUE regulation remain largely elusive. Here we report that the OsNLP3 (NIN-like protein 3) regulates NUE and grain yield in rice under N sufficient conditions. OsNLP3 transcript level is significantly induced by N starvation and its protein nucleocytosolic shuttling is specifically regulated by nitrate. Loss-of-function of OsNLP3 reduces plant growth, grain yield, and NUE under sufficient nitrate conditions, whereas under low nitrate or different ammonium conditions, osnlp3 mutants show no clear difference from the wild type. Importantly, under sufficient N conditions in the field, OsNLP3 overexpression lines display improved grain yield and NUE compared with the wild type. OsNLP3 orchestrates the expression of multiple N uptake and assimilation genes by directly binding to the nitrate-responsive cis-elements in their promoters. Overall, our study demonstrates that OsNLP3, together with OsNLP1 and OsNLP4, plays overlapping and differential roles in N acquisition and NUE, and modulates NUE and the grain yield increase promoted by N fertilizer. Therefore, OsNLP3 is a promising candidate gene for the genetic improvement of grain yield and NUE in rice.


Assuntos
Oryza , Grão Comestível/metabolismo , Fertilizantes , Nitratos/metabolismo , Nitrogênio/metabolismo , Oryza/genética , Oryza/metabolismo
4.
BMC Cancer ; 22(1): 1222, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443693

RESUMO

INTRODUCTION: Clinicians increasingly perform laparoscopic surgery for intrahepatic cholangiocarcinoma (ICC). However, this surgery can be difficult in patients with advanced-stage ICC because of the complicated procedures and difficulty in achieving high-quality results. We compared the effects of a three-step optimized procedure with a traditional procedure for patients with advanced-stage ICC. METHODS: Forty-two patients with advanced-stage ICC who received optimized laparoscopic hemihepatectomy with lymph node dissection (LND, optimized group) and 84 propensity score-matched patients who received traditional laparoscopic hemihepatectomy plus LND (traditional group) were analyzed. Surgical quality, disease-free survival (DFS), and overall survival (OS) were compared. RESULTS: The optimized group had a lower surgical bleeding score (P = 0.038) and a higher surgeon satisfaction score (P = 0.001). Blood loss during hepatectomy was less in the optimized group (190 vs. 295 mL, P < 0.001). The optimized group had more harvested LNs (12.0 vs. 8.0, P < 0.001) and more positive LNs (8.0 vs. 5.0, P < 0.001), and a similar rate of adequate LND (88.1% vs. 77.4%, P = 0.149). The optimized group had longer median DFS (9.0 vs. 7.0 months, P = 0.018) and median OS (15.0 vs. 13.0 months, P = 0.046). In addition, the optimized group also had a shorter total operation time (P = 0.001), shorter liver resection time (P = 0.001), shorter LND time (P < 0.001), shorter hospital stay (P < 0.001), and lower incidence of total morbidities (14.3% vs. 36.9%, P = 0.009). CONCLUSIONS: Our optimization of a three-step laparoscopic procedure for advanced ICC was feasible, improved the quality of liver resection and LND, prolonged survival, and led to better intraoperative and postoperative outcomes.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Laparoscopia , Humanos , Laparoscopia/efeitos adversos , Colangiocarcinoma/cirurgia , Hepatectomia/efeitos adversos , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos
5.
Acta Pharmacol Sin ; 42(5): 744-754, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32753731

RESUMO

Currently, dendritic cell-specific transmembrane protein (DC-STAMP), a multipass transmembrane protein, is considered as the master regulator of cell-cell fusion, which underlies the formation of functional multinucleated osteoclasts. Thus, DC-STAMP has become a promising target for osteoclast-associated osteolytic diseases. In this study, we investigated the effects of oridonin (ORI), a natural tetracyclic diterpenoid compound isolated from the traditional Chinese herb Rabdosia  rubescens, on osteoclastogenesis in vivo and ex vivo. ICR mice were injected with LPS (5 mg/kg, ip, on day 0 and day 4) to induce inflammatory bone destruction. Administration of ORI (2, 10 mg·kg-1·d-1, ig, for 8 days) dose dependently ameliorated inflammatory bone destruction and dramatically decreased DC-STAMP protein expression in BMMs isolated from LPS-treated mice. Treatment of preosteoclast RAW264.7 cells with ORI (0.78-3.125 µM) dose dependently inhibited both mRNA and protein levels of DC-STAMP, and suppressed the following activation of NFATc1 during osteoclastogenesis. Knockdown of DC-STAMP in RAW264.7 cells abolished the inhibitory effects of ORI on RANKL-induced NFATc1 activity and osteoclast formation. In conclusion, we show for the first time that ORI effectively attenuates inflammation-induced bone loss by suppressing DC-STAMP expression, suggesting that ORI is a potential agent against inflammatory bone diseases.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Diterpenos do Tipo Caurano/uso terapêutico , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Osteólise/tratamento farmacológico , Animais , Regulação para Baixo/efeitos dos fármacos , Feminino , Lipopolissacarídeos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Osteólise/induzido quimicamente , Osteólise/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
6.
Dig Dis Sci ; 66(4): 1063-1071, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32462510

RESUMO

BACKGROUND: Interferon regulatory factor 9 (IRF9) acts as a negative regulator of sirtuin-1 (SIRT1) to participate in many diseases. However, the role of SIRT1 and IRF9 in hyperlipidemia acute pancreatitis associated with kidney injury is unclear. AIMS: To explore the function of SIRT1 and IRF9 in hyperlipidemia acute pancreatitis associated with kidney injury and provide theoretical guidance for disease diagnosis and treatment. METHODS: Model rats were established by intraperitoneal injection of 20% L-arginine. Apoptosis of kidney tissue was determined by TUNEL staining. Expressions of IRF9, SIRT1, p53, and acetylated p53 were detected by qRT-PCR and Western blot. Dual-Luciferase Reporter Assay was carried out to validate the regulation of IRF9 on SIRT1. RESULTS: Pancreatic and renal injury was more serious, and apoptosis of kidney epithelial cells increased in acute pancreatitis (AP) and hyperlipidemia acute pancreatitis (HLAP) group. IRF9, p53, and acetylated p53 were up-regulated, and SIRT1 was down-regulated in AP and HLAP group (p < 0.05). Down-regulation of SIRT1 was negatively correlated with up-regulation of IRF9 in AP and HLAP group (p < 0.05). Pancreatic and renal injury and kidney epithelial cells apoptosis in HLAP group were more obvious than AP group (p < 0.05). The up-regulation of IRF9 and down-regulation of SIRT1 in HLAP group were more than AP group (p < 0.05). The promoter activity of SIRT1 was repressed by IRF9. CONCLUSION: In pancreatitis associated with kidney injury, IRF9 was a negative regulator of SIRT1, down-regulated the expression of SIRT1, increased acetylated p53, and promoted renal cell apoptosis. Hyperlipidemia further aggravated pancreatic and renal injury and renal cell apoptosis.


Assuntos
Hiperlipidemias , Fator Gênico 3 Estimulado por Interferon, Subunidade gama/metabolismo , Nefropatias , Pancreatite , Sirtuína 1/metabolismo , Animais , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Regulação para Baixo , Regulação da Expressão Gênica , Hiperlipidemias/complicações , Hiperlipidemias/metabolismo , Nefropatias/complicações , Nefropatias/metabolismo , Nefropatias/patologia , Pancreatite/etiologia , Pancreatite/metabolismo , Ratos , Índice de Gravidade de Doença , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo
7.
Mol Cell Biochem ; 472(1-2): 125-134, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32577948

RESUMO

Acute pancreatitis (AP) is an inflammatory disease caused by the abnormal activation of pancreatic enzymes in the pancreas, with a considerably high morbidity and mortality. However, the etiological factor and pathogenesis of AP are still unclear. This study was aimed to explore the role and mechanism of interferon regulatory factor 9 (IRF9) in the occurrence of AP and to provide experimental and theoretical foundation for AP diagnosis and treatment. AP model in vitro was established by caerulein-induced group. Small interfering RNA (siRNA) was designed and constructed to silence IRF9 gene. After siRNA transfected and caerulein treated successfully, the expression levels of IRF9, SIRT1, and acetylated p53 (Ac-p53) were determined by qRT-PCR and Western blot. The apoptosis, proliferation, and migration of AR42J cells were checked by flow cytometry, MTT, and transwell assay. Dual-luciferase reporter assay was implemented to validate the regulatory effect of IRF9 on SIRT1. Here, our study showed that the expression of IRF9 and Ac-p53 was increased, SIRT1 was decreased, and cell apoptosis, proliferation, and migration of AR42J cells were increased after caerulein induced. IRF9 gene silencing upregulated SIRT1, downregulated Ac-p53, and inhibited cell apoptosis, proliferation, and migration. Dual-Luciferase reporter assay showed that IRF9 could negatively regulate SIRT1. The potential mechanism was that IRF9 could modulate cell apoptosis, proliferation, migration, and bind the promoter of SIRT1 to repress SIRT1-p53. It hinted that IRF9 showed a novel function in AP by modulating cell apoptosis, proliferation, migration, and suppressing SIRT1-p53. IRF9 might be a good potential treatment target for AP.


Assuntos
Apoptose , Movimento Celular , Proliferação de Células , Fator Gênico 3 Estimulado por Interferon, Subunidade gama/metabolismo , Pancreatite/patologia , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Biomarcadores/metabolismo , Células Cultivadas , Regulação da Expressão Gênica , Fator Gênico 3 Estimulado por Interferon, Subunidade gama/genética , Pancreatite/genética , Pancreatite/metabolismo , Ratos , Sirtuína 1/genética , Proteína Supressora de Tumor p53/genética
8.
Acta Pharmacol Sin ; 41(2): 229-236, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31431733

RESUMO

In chronic infectious diseases caused by gram-negative bacteria, such as osteomyelitis, septic arthritis, and periodontitis, osteoclastic activity is enhanced with elevated inflammation, which disturbs the bone homeostasis and results in osteolysis. Lipopolysaccharide (LPS), as a bacteria product, plays an important role in this process. Recent evidence shows that an antimalarial drug artesunate attenuates LPS-induced osteolysis independent of RANKL. In this study we evaluated the effects of artesunate on LPS-induced osteoclastogenesis in vitro and femur osteolysis in vivo, and explored the mechanisms underlying the effects of artesunate on LPS-induced osteoclast differentiation independent of RANKL. In preosteoclastic RAW264.7 cells, we found that artesunate (1.56-12.5 µM) dose dependently inhibited LPS-induced osteoclast formation accompanied by suppressing LPS-stimulated osteoclast-related gene expression (Fra-2, TRAP, Cathepsin K, ß3-integrin, DC-STAMP, and Atp6v0d2). We showed that artesunate (3.125-12.5 µM) inhibited LPS-stimulated nuclear factor of activated T cells c1 (NFATc1) but not NF-κB transcriptional activity; artesunate (6.25, 12.5 µM) significantly inhibited LPS-stimulated NFATc1 protein expression. Furthermore, artesunate treatment markedly suppressed LPS-induced Ca2+ influx, and decreased the expression of PP2B-Aα (calcineurin) and pPLCγ1 in the cells. In addition, artesunate treatment significantly decreased the expression of upstream signals TLR4 and TRAF6 during LPS-induced osteoclastogenesis. Administration of artesunate (10 mg/kg, ip) for 8 days effectively inhibited serum TNF-α levels and ameliorated LPS (5 mg/kg, ip)-induced inflammatory bone loss in vivo. Taken together, artesunate attenuates LPS-induced inflammatory osteoclastogenesis by inhibiting the expression of TLR4/TRAF6 and the downstream PLCγ1-Ca2+-NFATc1 signaling pathway. Artesunate is a valuable choice to treat bone loss induced by gram-negative bacteria infection or inflammation in RANKL-independent pathway.


Assuntos
Antimaláricos/farmacologia , Artesunato/farmacologia , Inflamação/tratamento farmacológico , Osteoclastos/efeitos dos fármacos , Animais , Antimaláricos/administração & dosagem , Artesunato/administração & dosagem , Cálcio/metabolismo , Relação Dose-Resposta a Droga , Feminino , Inflamação/patologia , Lipopolissacarídeos , Camundongos , Camundongos Endogâmicos ICR , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/citologia , Osteogênese/efeitos dos fármacos , Fosfolipase C gama/metabolismo , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Fator 6 Associado a Receptor de TNF/metabolismo , Receptor 4 Toll-Like/metabolismo
9.
Clin Lab ; 65(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414744

RESUMO

BACKGROUND: Recently, long non-coding RNAs (lncRNAs) have attracted substantial attention owing to their unforeseen critical roles in a wide range of biological processes. The aim of our study was to provide an overview of lncRNA expression profiles in plasma of RA patients. METHODS: The Agilent LncRNA + mRNA Human Gene Expression Microarray V4.0 was employed to determine differentially expressed (DE) lncRNAs and mRNAs in plasma of four female newly diagnosed and DMARD-naïve RA patients and four female age-matched healthy controls. The KOBAS (KEGG Orthology Based Annotation System) software was applied to determine the gene ontology (GO) terms and pathway in which the DE mRNAs were enriched. Furthermore, a lncRNA-mRNA co-expression network was constructed according to the correlation between DE lncRNAs and mRNAs. RESULTS: Compared with healthy controls, a total of 289 DE lncRNAs (169 up-regulated and 120 down-regulated) and 468 DE mRNAs (280 up-regulated and 188 down-regulated) were found in the plasma of patients with RA. Bioinformatics analysis indicated that the DE mRNAs might be involved in the pathogenesis of RA mainly through platelets. In addition, a co-expression network composed of 229 network nodes and 340 connections between 116 lncRNAs and 113 mRNAs was constructed. CONCLUSIONS: We characterized the plasma lncRNA expression profiles in RA patients for the first time. Our results could shed new light on the pathogenesis of RA and help identify lncRNAs as novel diagnostic biomarkers and therapeutic targets for RA.


Assuntos
Artrite Reumatoide/genética , Biomarcadores/metabolismo , Perfilação da Expressão Gênica/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , RNA Longo não Codificante/genética , Adulto , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Biomarcadores/sangue , Biologia Computacional , Feminino , Ontologia Genética , Redes Reguladoras de Genes/genética , Humanos , Pessoa de Meia-Idade , RNA Longo não Codificante/sangue , RNA Mensageiro/sangue , RNA Mensageiro/genética , Transdução de Sinais/genética
10.
J Clin Lab Anal ; 33(5): e22862, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30779461

RESUMO

BACKGROUND: Emerging evidence indicates that some hematological markers have critical value in evaluating treatment response. This study was performed to determine the clinical value of hemoglobin (Hb), platelet (Plt), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ). METHODS: Fifty-two RA patients receiving TCZ were recruited and followed for 6 months. The values of abovementioned hematological markers were collected. Clinical disease activity index (CDAI) and disease activity score based on 28 joints (DAS28)-ESR were calculated. Correlation analysis was conducted by calculating Pearson's correlation coefficient. The change in disease activity between groups according to the baseline level of hematological markers was compared by t test. RESULTS: Significant correlation between change in NLR (△NLR), change in PLR (△PLR), and change in CDAI (△CDAI) was found (△NLR: r = 0.30, P = 0.03; △PLR: r = 0.31, P = 0.03). The change in Plt (△Plt) was correlated with change in DAS28-ESR (△DAS28-ESR) (r = 0.36, P = 8.24 × 10-3 ). Greater improvement in CDAI was seen in patients categorized into Plt high group (t = 2.06, P = 0.04), NLR high group (t = 2.15, P = 0.04), and PLR high group (t = 2.41, P = 0.02) compared with the contrast group. CONCLUSION: Our study demonstrated that △Plt, △NLR, and △PLR could be used to monitor the clinical response to TCZ. RA patients with high baseline levels of Plt, NLR, and PLR achieved more improvement, indicating these hematological markers might be utilized to guide TCZ treatment.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Biomarcadores/sangue , Adulto , Artrite Reumatoide/etiologia , Feminino , Hemoglobinas/análise , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Contagem de Plaquetas , Estudos Prospectivos , Resultado do Tratamento
11.
Phytother Res ; 33(1): 214-223, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30375049

RESUMO

Cardiac fibrosis contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. Antifibrotic therapies are likely to be a crucial strategy in curbing many fibrosis-related cardiac diseases. In our previous study, an ethyl acetate extract of a traditional Chinese medicine Aristolochia yunnanensis Franch. was found to have a therapeutic effect on myocardial fibrosis in vitro and in vivo. However, the exact chemicals and their mechanisms responsible for the activity of the crude extract have not been illustrated yet. In the current study, 10 sesquiterpenoids (1-10) were isolated from the active extract, and their antifibrotic effects were systematically evaluated in transforming growth factor ß 1 (TGFß1)-stimulated cardiac fibroblasts and NIH3T3 fibrosis models. (+)-Isobicyclogermacrenal (1) and spathulenol (2) were identified as the main active components, being more potent than the well-known natural antifibrotic agent oxymatrine. Compounds 1 and 2 could inhibit the TGFß1-induced cardiac fibroblasts proliferation and suppress the expression of the fibrosis biomarkers fibronectin and α-smooth muscle actin via down-regulation of their mRNA levels. The mechanism study revealed that 1 and 2 could inhibit the phosphorylation of TGFß type I receptor, leading to the decrease of the phosphorylation levels of downstream Smad2/3, then consequently blocking the nuclear translocation of Smad2/3 in the TGFß/Smad signaling pathway. These findings suggest that 1 and 2 may serve as promising natural leads for the development of anticardiac fibrosis drugs.


Assuntos
Aldeídos/uso terapêutico , Aristolochia/química , Fibrose/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Sesquiterpenos/uso terapêutico , Fator de Crescimento Transformador beta/metabolismo , Aldeídos/farmacologia , Animais , Fibrose/patologia , Humanos , Masculino , Camundongos , Mães , Ratos Sprague-Dawley , Sesquiterpenos/farmacologia , Transdução de Sinais
12.
Molecules ; 23(5)2018 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-29751627

RESUMO

Caulophyllum robustum Maxim is widely distributed in China and used as a traditional herbal medicine to induce childbirth, ease the pain of labor, rectify delayed or irregular menstruation, alleviate heavy bleeding and pain during menstruation, and treat external injuries and irregular menses. According to our detailed chemical investigation, three new triterpene derivatives (1⁻3), together with seven known compounds, were isolated from the root and rhizome of C. robustum Maxim. Their structures were elucidated by 1D- and 2D-NMR spectroscopic analysis and physio-chemical methods. They were identified as (1) 23-hydroxy-3,19-dioxo-olean-12-en-28-oic-acid; (2) 23-hydroxy-3,11-dioxo-olean-12-en-28-oic acid; and (3) 16α,23-dihydroxy-3-oxo-olean-12-en-28-oic acid. Compounds (1⁻10) inhibited the LPS-activated NO production in RAW264.7 cells. Furthermore, the anti-inflammatory characteristics of these compounds were confirmed on the basis of decreases in iNOS and NF-κB protein expression in RAW264.7 cells.


Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Caulophyllum/química , Triterpenos/química , Triterpenos/farmacologia , Animais , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Células RAW 264.7
13.
Org Biomol Chem ; 16(1): 57-61, 2017 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-29226933

RESUMO

Highly stereoselective syntheses of chiral indolines and tetrahydroquinolines are achieved by combining the asymmetric Zn-mediated allylation of chiral N-tert-butanesulfinyl imines with efficient intramolecular C-N cross-coupling. Herein, the advantages of such a synthetic strategy are illustrated by the synthesis of indolines and tetrahydroquinolines with quaternary stereocenters and multi-substituted 1-oxo-1,2,3,4-tetrahydroisoquinolines.

14.
Yao Xue Xue Bao ; 52(3): 443-8, 2017 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-29979858

RESUMO

Donafenib is the deuterium derivative of sorafenib, and is an anti-tumor drug in clinical trials. An accurate and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of donafenib and its N-oxide metabolite in human plasma. The analytes and internal standards (sorafenib and sorafenib N-oxide) were extracted from plasma by protein precipitation with acetonitrile, and separated on a Gemini C18 (50 mm × 2.0 mm, 5 µm) column using a gradient elution procedure. The mobile phase consisted of acetonitrile and 5 mmol ·L−1 ammonium acetate (0.2% formic acid) at a flow rate of 0.7 mL·min−1. The total run time was 5.0 min. Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 468.2 → 273.2 for donafenib and m/z 465.2 → 270.2 for its internal standard sorafenib, m/z 484.2 → 289.2 for donafenib N-oxide and m/z 481.2 → 286.2 for its internal standard sorafenib N-oxide. The standard curves were linear in the range of 5.00−5 000 ng·mL−1 for donafenib, and 1.00−1 000 ng·mL−1 for donafenib N-oxide. The method was validated and successfully applied to the pharmacokinetics study of donafenib tosylate tablets in volunteers.


Assuntos
Niacinamida/análogos & derivados , Compostos de Fenilureia/sangue , Compostos de Fenilureia/farmacocinética , Inibidores de Proteínas Quinases/sangue , Inibidores de Proteínas Quinases/farmacocinética , Antineoplásicos/sangue , Antineoplásicos/farmacocinética , Cromatografia Líquida , Humanos , Niacinamida/sangue , Niacinamida/farmacocinética , Óxidos , Plasma , Reprodutibilidade dos Testes , Sorafenibe , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
15.
Biomed Environ Sci ; 29(9): 683-685, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27806751

RESUMO

We designed two types of pre-adaption plans for this study. One was a pre-adaption training with progressive intermittent hypoxia, with a constant lower pressure oxygen tank used in the plain before arriving at the plateau (PG). The other was by progressively increasing the time of exposure to hypoxia with oxygen supplied in stages after radical plateau (RG). By testing the blood oxygen saturation (SpO2), heart rate (HR), and quality of sleep after arriving at the 3800 m high plateau, results showed that the pre-acclimatization and radical groups performed better than the control group (CG). Both strategies were equivalent in terms of effects and principles in providing more flexible choices for acclimatization.


Assuntos
Adaptação Fisiológica , Hipóxia/metabolismo , Oxigênio/metabolismo , Aclimatação , Meio Ambiente , Frequência Cardíaca , Humanos , Hipóxia/fisiopatologia
16.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(6): 1921-4, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-30053354

RESUMO

The finite bandwidth of spectroradiometers always causes significant errors when the measured light source has a narrow bandwidth compared to that of spectroradiometers. In order to solve this problem, an improved correction approach which is called seven-point correction approach is proposed. Firstly, the seven-point correction formula is obtained with Taylor's series and related derivative formula. Secondly, the effect of seven-point formula is validated through a simulated spectrum with a sine function shape. Considering the sine function as true spectrum, we calculate the measured spectrum with the bandpass function of spectroradiometers. We also correct the measured spectrum with the seven-point formula. At last, we validate the seven-point formula experimentally with a LED lamp whose center wavelength is 365 nm. Using a double grating monochromator, we measure the irradiance of LED lamp when the bandwidth of spectroradiometer is 5 and 0.5 nm. We also obtain the corrected spectrum by applying seven-point formula to measured spectrum. The simulated results show that, the corrected value at the center wavelength could be above 99% of the true value. The experimental results show that, the corrected value at the center wavelength could reach above 95% of the true value. Above all, the proposed seven-point approach has an improved correction effect compared with three-point and five point approach. This correction approach could be widely applied in the field of spectrum measurement.

17.
J Pharmacol Sci ; 126(3): 216-29, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25341683

RESUMO

Among the various cancer cell lines, HeLa cells were found to be sensitive to pterostilbene (Pte), a compound that is enriched in small fruits such as grapes and berries. However, the mechanism involved in the cytotoxicity of Pte has not been fully characterized. Using biochemical and free radical biological experiments in vitro, we identified the pro-apoptotic profiles of Pte and evaluated the level of redox stress-triggered ER stress during HeLa cell apoptosis. The data showed a strong dose-response relationship between Pte exposure and the characteristics of HeLa apoptosis in terms of changes in apoptotic morphology, DNA fragmentation, and activated caspases in the intrinsic apoptotic pathway. During drug exposure, alterations in the intracellular redox homeostasis that favor oxidation were necessary to cause ER stress-related apoptosis, as demonstrated by enzymatic and non-enzymatic redox modulators. A statistically significant and dose-dependent increase (P < 0.05) was found with regard to the unique expression levels of Nrf2/ARE downstream target genes in HeLa cells undergoing late apoptosis, levels that were restored with anti-oxidant application with the Pte treatment. Our research demonstrated that Pte trigged ER stress by redox homeostasis imbalance, which was negatively regulated by a following activation of Nrf2.


Assuntos
Adenocarcinoma/patologia , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estilbenos/farmacologia , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Células HeLa , Humanos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo
18.
J Nanosci Nanotechnol ; 14(7): 5047-53, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24757979

RESUMO

A novel Fe3O4@ZnS nanomaterial with fluorescent and superparamagnetic properties has been successfully fabricated via TOPO-TOP synthesis with an additional coordinating component (OAm). The adsorption of OAm on the preformed magnetite nanoparticles, which were prepared in phenyl ether with oleic acid and oleyl amine, played an essential role in directing the structure of the Fe3O4@ZnS composites. The obtained materials were characterized by FTIR, TEM, XRD, X-ray photoelectron spectroscopy (XPS), UV-vis, fluorescence spectrophotometer and VSM. The results indicated that the Fe3O4 nanoparticles were successfully combined with ZnS and the coating of ZnS can be controlled by adjusting the molar ratio of Fe3O4 to ZnS. The saturation magnetization values of Fe3O4, Fe3O4@ZnS (1:2) and Fe3O4@ZnS (1:5) nanoparticles are 57.0 emu g(-1), 44.4 emu g(-1) and 34.2 emu g(-1), respectively at 300 K and the nanocomposites exhibit better fluorescence without evident quenching. The combined magnetic and fluorescent properties endow the nanocomposites with great potential applications in "nano-conveyer-belt" platform technology for drug targeting, bioseparation, diagnostic analysis and so on.

19.
Ann Med ; 56(1): 2389470, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39126262

RESUMO

BACKGROUND: Previous meta-analyses have investigated the efficacy of lipid-lowering therapies for atherosclerotic cardiovascular disease; however, few have focused on patients with acute coronary syndrome (ACS). This meta-analysis aimed to compare the benefits of intensive lipid-lowering therapy with those of background statin therapy in patients with ACS. METHODS: Searches were performed on PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for articles published until April 13, 2023. Randomized controlled trials that compared intensive lipid-lowering therapies and background statin therapies in patients with prior ACS and recorded the outcome of three-point major cardiovascular events (MACE) were included. The risk ratio (RR) with 95% confidence interval (CI) was used as a measure of primary and secondary outcomes. RESULTS: Nine trials involving 38,640 patients with ACS were identified. Pooled results suggested that intensive lipid-lowering therapies are associated with a reduction in the risk of three-point MACE (RR, 0.88; 95% CI, 0.83-0.94; p < 0.001), recurrent ACS (RR, 0.82; 95% CI, 0.71-0.96; p = 0.013), nonfatal myocardial infarction (MI) (RR, 0.87; 95% CI, 0.81-0.93; p < 0.001), stroke (RR, 0.83; 95% CI, 0.73-0.94; p = 0.003), and unstable angina-related hospitalization (RR, 0.57; 95% CI, 0.33-0.99; p = 0.046), but not all-cause mortality (RR, 0.94; 95% CI, 0.82-1.07; p = 0.329), cardiovascular disease-related mortality (RR, 0.96; 95% CI, 0.88-1.06; p = 0.457) or coronary revascularization (RR, 0.89; 95% CI, 0.79-1.00; p = 0.057). CONCLUSIONS: Intensive lipid-lowering therapies may reduce the risk of three-point MACE, recurrent ACS, nonfatal MI, stroke, and hospitalization for unstable angina in patients with ACS undergoing background statin therapy. These results may assist in clinical decision-making for the secondary prevention of cardiovascular events to initiate intensive lipid-lowering therapies immediately after ACS.


Assuntos
Síndrome Coronariana Aguda , Inibidores de Hidroximetilglutaril-CoA Redutases , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/mortalidade , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Hipolipemiantes/uso terapêutico , Hipolipemiantes/administração & dosagem , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Resultado do Tratamento , Hospitalização/estatística & dados numéricos , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/epidemiologia
20.
J Neurosci Methods ; 403: 110049, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38151187

RESUMO

BACKGROUND: Dynamic spatial functional network connectivity (dsFNC) has shown advantages in detecting functional alterations impacted by mental disorders using magnitude-only fMRI data. However, complete fMRI data are complex-valued with unique and useful phase information. METHODS: We propose dsFNC of spatial source phase (SSP) maps, derived from complex-valued fMRI data (named SSP-dsFNC), to capture the dynamics elicited by the phase. We compute mutual information for connectivity quantification, employ statistical analysis and Markov chains to assess dynamics, ultimately classifying schizophrenia patients (SZs) and healthy controls (HCs) based on connectivity variance and Markov chain state transitions across windows. RESULTS: SSP-dsFNC yielded greater dynamics and more significant HC-SZ differences, due to the use of complete brain information from complex-valued fMRI data. COMPARISON WITH EXISTING METHODS: Compared with magnitude-dsFNC, SSP-dsFNC detected additional and meaningful connections across windows (e.g., for right frontal parietal) and achieved 14.6% higher accuracy for classifying HCs and SZs. CONCLUSIONS: This work provides new evidence about how SSP-dsFNC could be impacted by schizophrenia, and this information could be used to identify potential imaging biomarkers for psychotic diagnosis.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Cadeias de Markov
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