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1.
J Proteome Res ; 23(5): 1713-1724, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38648079

RESUMO

Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirinhigh/ODC1high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.


Assuntos
Autofagia , Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Progressão da Doença , Neoplasias Pulmonares , Ornitina Descarboxilase , Feminino , Humanos , Masculino , Células A549 , Autofagia/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Ornitina Descarboxilase/metabolismo , Ornitina Descarboxilase/genética , Prognóstico , Regulação para Cima
2.
BMC Cancer ; 24(1): 913, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39080593

RESUMO

BACKGROUND: In China, the national cervical cancer screening protocol involves initial testing for high-risk human papillomavirus (hrHPV), followed by cytology for hrHPV-positive cases. This study evaluates the effectiveness of PAX1 methylation (PAX1m) analysis in identifying precancerous or cancerous lesions in cervical samples from Chinese women positive for non-16/18 hrHPV strains. METHODS: Between February 2022 and March 2023, 281 cervical samples from non-16/18 hrHPV-positive women underwent cytological examination and PAX1m analysis. The study assessed the statistical relationship between PAX1m levels and the presence of cervical lesions, comparing the diagnostic performance of PAX1m to conventional cytology. RESULTS: A significant association was found between PAX1 methylation levels and the risk of CIN2 + and CIN3 + lesions, with 47 instances of CIN2 + detected. Odds ratios (ORs) for moderate and high PAX1m levels were 8.86 (95% CI: 2.24-42.17) and 166.32 (95% CI: 47.09-784.97), respectively. The area under the ROC curve for PAX1m in identifying CIN2 + lesions was 0.948 (95% CI: 0.895-0.99). PAX1m demonstrated similar sensitivity and negative predictive value (NPV) to cytology but reduced the colposcopy referral rate from 47.7% with cytology alone to 25.6% with PAX1m, showing superior specificity and positive predictive value across age groups. CONCLUSIONS: PAX1 methylation is a strong indicator of CIN2 + and CIN3 + risk, offering diagnostic performance comparable to cytology with the added benefit of reduced unnecessary colposcopy referrals. These findings support the use of PAX1m analysis as a reliable tool for triaging non-16/18 hrHPV-positive women in outpatient settings.


Assuntos
Metilação de DNA , Detecção Precoce de Câncer , Fatores de Transcrição Box Pareados , Infecções por Papillomavirus , Triagem , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/genética , Pessoa de Meia-Idade , Detecção Precoce de Câncer/métodos , Adulto , Fatores de Transcrição Box Pareados/genética , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Triagem/métodos , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/virologia , Displasia do Colo do Útero/genética , China/epidemiologia , Idoso , Curva ROC , Biomarcadores Tumorais/genética , Esfregaço Vaginal
3.
Nanotechnology ; 35(35)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38806006

RESUMO

Artificially synthesized DNA is involved in the construction of a library of oil tracers due to their unlimited number and no-biological toxicity. The strategy of the construction is proposed by oleophilic Silica-encapsulated DNA nanoparticles, which offers fresh thinking in developing novel tracers, sensors, and molecular machines in engineering & applied sciences based on artificially synthesized DNA blocks.


Assuntos
DNA , Nanopartículas , Dióxido de Silício , Dióxido de Silício/química , DNA/química , Nanopartículas/química , Óleos/química
4.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1872-1881, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38812199

RESUMO

This study aims to identify the active constituents of essential oil from the rhizomes of Curcuma phaeocaulis for the treatment of dysmenorrhea. The compounds were separated and purified by molecular distillation, silica gel and Sephadex LH-20 column chromatography, preparative thin layer chromatography, and semi-preparative high performance liquid chromatography. Their structures were identified by mass spectrometry and nuclear magnetic resonance spectroscopy. The animal model of primary dysmenorrhea and the contraction model of isolated uterine smooth muscle of rats were established to examine the active constituents in the essential oil for treating dysmenorrhea. Six sesquiterpenes were isolated and identified as dehydrocommiterpene A(1), comosone Ⅱ(2), 5α(H)-eudesma-3(4),7(11)-dien-9ß-ol-6-one(3), guaia-6(7)-en-11-ol(4), curcumenol(5), and isocurcumenol(6), among which compound 1 was a novel compound. The animal experiments showed that the essential oil from C. phaeocaulis significantly lowered the level of PGF_(2α) in uterine tissue compared with the model group. The experiment with the contraction model of isolated uterine smooth muscle demonstrated that the components with high boiling points outperformed those with low boiling points in relaxing the uterine smooth muscle, and compounds 1, 2, 5, and 6 isolated from the fraction with a high boiling point had the effect of relaxing the uterine smooth muscle. Among them, compounds 5 and 6 inhibited the extracellular Ca~(2+) influx and intracellular Ca~(2+) release to relax the uterine smooth muscle. In conclusion, the components with high boiling points and sesquiterpenes are the active components in the essential oil of C. phaeocaulis for treating dysmenorrhea.


Assuntos
Curcuma , Dismenorreia , Óleos Voláteis , Dismenorreia/tratamento farmacológico , Feminino , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Animais , Curcuma/química , Ratos , Ratos Sprague-Dawley , Humanos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Útero/efeitos dos fármacos , Rizoma/química
5.
Plant Cell Rep ; 42(9): 1419-1431, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37326841

RESUMO

KEY MESSAGE: The deletion mutated rpoC2 leads to yellow stripes of Clivia miniata var. variegata by down regulating the transcription of 28 chloroplast genes and disturbing chloroplast biogenesis and thylakoid membrane development. Clivia miniata var. variegata (Cmvv) is a common mutant of Clivia miniata but its genetic basis is unclear. Here, we found that a 425 bp deletion mutation of chloroplast rpoC2 underlies the yellow stripes (YSs) of Cmvv. Both RNA polymerase PEP and NEP coexist in seed-plant chloroplasts and the ß″ subunit of PEP is encoded by rpoC2. The rpoC2 mutation changed the discontinuous cleft domain required to form the PEP central cleft for DNA binding from 1103 to 59 aa. RNA-Seq revealed that 28 chloroplast genes (cpDEGs) were all down-regulated in YSs, of which, four involved in chloroplast protein translation and 21 of photosynthesis system (PS)I, PSII, cytochrome b6/f complex and ATP synthase are crucial for chloroplast biogenesis/development. The accuracy and reliability of RNA-Seq was verified by qRT-PCR. Moreover, the chlorophyll (Chl) a/b content, ratio of Chla/Chlb and photosynthetic rate (Pn) of YS decreased significantly. Meanwhile, chloroplasts of the YS mesophyll cells were smaller, irregular in shape, contain almost no thylakoid membrane, and even proplastid was found in YS. These findings indicate that the rpoC2 mutation down-regulated expression of the 28 cpDEGs, which disturb chloroplast biogenesis and its thylakoid membrane development. Thus, there are not enough PSI and II components to bind Chl, so that the corresponding areas of the leaf are yellow and show a low Pn. In this study, the molecular mechanism of three phenotypes of F1 (Cmvv ♀ × C. miniata ♂) was revealed, which lays a foundation for the breeding of variegated plants.


Assuntos
Amaryllidaceae , Melhoramento Vegetal , Reprodutibilidade dos Testes , Cloroplastos/metabolismo , Mutação/genética , Folhas de Planta/metabolismo , Amaryllidaceae/genética , Deleção de Sequência , Regulação da Expressão Gênica de Plantas/genética
6.
Molecules ; 28(3)2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36771160

RESUMO

Four novel indane derivatives, anisotindans A-D (1-4), were isolated from the roots of Anisodus tanguticus. Their structures were established using comprehensive spectroscopic analyses, and their absolute configurations were determined by electronic circular dichroism (ECD) calculations and single-crystal X-ray diffraction analyses. Anisotindans C and D (3 and 4) are two unusual indenofuran analogs. ABTS•+ and DPPH•+ assays of radical scavenging activity reveal that all compounds (1-4) are active. Specifically, the ABTS•+ assay results show that anisotindan A (1) exhibits the best antioxidant activity with an IC50 value of 15.62 ± 1.85 µM (vitamin C, IC50 = 22.54 ± 5.18 µM).


Assuntos
Antioxidantes , Antioxidantes/farmacologia , Antioxidantes/química , Estrutura Molecular
7.
Mol Biol Rep ; 49(3): 1925-1934, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34860320

RESUMO

BACKGROUND: Lycium ruthenicum is an eco-economic shrub which can exist in two forms, thorny and thornless under varying soil moisture conditions. The aim of this study was to determine if the two forms of L. ruthenicum were influenced by soil water content (SWC) and to test the three-way link among SWC, occurrence of branch-thorn and DNA methylation modification. METHODS AND RESULTS: Here, pot experiment was carried out to reveal the influence of SWC on the occurrence of branch-thorn and then paraffin sections, scanning electron microscope and methylation-sensitive amplification polymorphism(MSAP) analysis were used to determine the three-way link among SWC, branch-thorn occurrence and DNA methylation. The results showed that (a) soil drought promoted the development of thorn primordium into branch-thorn and (b) branch-thorn covered axillary bud to protect it against drought and other stresses; (c) the branch-thorn occurrence response to drought was correlated with hypermethylation of CCGG sites and (d) thorny and thornless plants of a clone were distinguished successfully based on the MSAP profiles of their leaves. CONCLUSIONS: Branch-thorns of the L. ruthenicum clone, which occurred in response to drought, covered axillary buds to protect them against drought and other stresses; thorn primordium of the clone did not develop into branch-thorn under the adequate soil moisture condition. The occurrence and absence of the branch-thorns were correlated with the hyper- and hypo-methylation, respectively. We proposed that the branch-thorn plasticity might be an adjustment strategy for the environment, which seems to support the theory of "Use in, waste out".


Assuntos
Lycium , DNA , Metilação de DNA/genética , Lycium/genética , Folhas de Planta/genética , Solo , Água
8.
Bioorg Chem ; 127: 105970, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35749854

RESUMO

Six pairs of enantiomeric phthalide dimers (1-6) were isolated from the rhizomes of Ligusticum chuanxiong. Their structures and absolute configurations were elucidated by NMR spectroscopy, X-ray diffraction analyses, and electronic circular dichroism calculations. Compounds (+)-1 and (-)-1 are new phthalide dimers, featuring two classes of monomeric units (a phthalide and an unusual 2,3-seco-phthalide) with an uncommon linkage (3,6'/8,3'a). Compounds (+)-2 and (-)-3 are also novel phthalide dimers that had not been reported previously. Although (-)-2 and (+)-3 have been successfully isolated in previous studies, their absolute configurations were not unambiguously determined. As for compound 4, it was reported as a racemate in one study, and one of its enantiomers was identified in a subsequent study. Herein, all enantiomeric phthalide dimers were successfully separated, and their absolute configurations were determined. The inhibitory effects of all isolates against lipopolysaccharide-induced nitric oxide production were tested using RAW264.7 cells. The results show that compounds (+)-2, (-)-2, (+)-3, (-)-3, (+)-4, (-)-4, (+)-5, (+)-6, and (-)-6 have inhibitory activities, with compound (+)-5 being the most active (IC50 value of 4.3 ± 1.3 µM).


Assuntos
Benzofuranos , Ligusticum , Anti-Inflamatórios/farmacologia , Benzofuranos/química , Benzofuranos/farmacologia , Ligusticum/química , Estrutura Molecular , Rizoma/química
9.
Molecules ; 27(18)2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-36144834

RESUMO

Perilla frutescens (L.) Britt. (Labiatae), a medicinal plant, has been widely used for the therapy of multiple diseases since about 1800 years ago. It has been demonstrated that the extracts of P. frutescens exert significant anti-inflammatory effects. In this research, two pairs of 7,7'-cyclolignan enantiomers, possessing a cyclobutane moiety, (+)/(-)-perfrancin [(+)/(-)-1] and (+)/(-)-magnosalin [(+)/(-)-2], were separated from P. frutescens leaves. The present study achieved the chiral separation and determined the absolute configuration of (±)-1 and (±)-2. Compounds (+)-1 and (-)-1 have notable anti-inflammatory effects by reducing the secretion of pro-inflammatory factors (NO, TNF-α and IL-6) and the expression of pro-inflammatory mediators (iNOS and COX-2). These findings indicate that cyclolignans are effective substances of P. frutescens with anti-inflammatory activity. The present study partially elucidates the mechanisms underlying the effects of P. frutescens.


Assuntos
Ciclobutanos , Perilla frutescens , Perilla , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2 , Mediadores da Inflamação , Interleucina-6 , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa
10.
Zhongguo Zhong Yao Za Zhi ; 47(12): 3265-3269, 2022 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-35851120

RESUMO

Macroporous resin chromatography, silica gel column chromatography, preparative thin layer chromatography, and semi-preparative high performance liquid chromatography were performed to isolate two compounds from the acid extract of the lateral roots of Aconitum carmichaelii: a new 9-phenylisoquinoline alkaloid(1) and a known pavine alkaloid(2). Their structures were elucidated by spectroscopy. The absolute configuration of compound 1 was identified by electronic circular dichroism(ECD) and it was determined to be(aS)-7,8-dimethoxy-9-(2-carboxy-4,5-dimethoxyphenyl)-3,4-dihydroisoquinoline-1(2H)-one(1). The cardioprotective effects of 1 and 2 against doxorubicin-induced toxicity in H9 c2 cells were evaluated. Both of the isoquinoline alkaloids showed cardioprotective activity.


Assuntos
Aconitum , Alcaloides , Medicamentos de Ervas Chinesas , Aconitum/química , Alcaloides/análise , Alcaloides/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Raízes de Plantas/química
11.
Zhongguo Zhong Yao Za Zhi ; 47(20): 5530-5536, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36471969

RESUMO

This study investigated the chemical components from the florets of Carthamus tinctorius. Five compounds were isolated from C. tinctorius by column chromatography with silica gel and toyopearl HW-40 F, preparative thin-layer chromatography(TLC), and semi-preparative reverse phased high performance liquid chromatography(RP-HPLC). Their structures were identified by mass spectrometry(MS), one-dimension nuclear magnetic resonance(1 D-NMR), two-dimension nuclear magnetic resonance(2 D-NMR), and single-crystal X-ray diffraction as(-)-(2S,3S,5S,7S,10R)-eudesma-4(15)-en-2,3,11-triol(1 a),(+)-(2R,3R,5R,7R,10S)-eudesma-4(15)-en-2,3,11-triol(1 b), rosin(2),(+)-syringaresinol(3), and(E)-1-(4'-hydroxyphenyl)-but-1-en-3-one(4). Compounds 1 a and 1 b are a pair of enantiomeric sesquiterpenoids. Compound 1 a is a new eudesmene and is named(-)-plucheol A. Compound 1 a at 100 µmol·L~(-1) showed significant antioxidant activity against ABTS~(+·) and DPPH·, with the scavenging rates of 30.98%±4.17% and 27.52%±1.24%, respectively, while compound 1 b was inactive. In addition, compounds 1 a and 1 b showed no obvious anti-inflammatory activity.


Assuntos
Carthamus tinctorius , Sesquiterpenos , Carthamus tinctorius/química , Cromatografia Líquida de Alta Pressão/métodos , Sesquiterpenos/química , Estereoisomerismo , Espectrometria de Massas , Estrutura Molecular
12.
BMC Cancer ; 21(1): 559, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001062

RESUMO

BACKGROUND: As an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression, KDM6B has been implicated in the development and malignant progression in various types of cancers. However, its potential roles in esophageal squamous cell carcinoma (ESCC) have not been explored. METHODS: The expression of KDM6B in human ESCC tissues and cell lines was examined using RT-qPCR, immunohistochemical staining and immunoblotting. The effects of KDM6B on the proliferation and metastasis of ESCC were examined using in vitro and in vivo functional tests. RNA-seq and ChIP-seq assay were used to demonstrate the molecular biological mechanism of KDM6B in ESCC. RESULTS: We show that the expression level of KDM6B increased significantly in patients with lymph node metastasis. Furthermore, we confirmed that KDM6B knockdown reduces proliferation and metastasis of ESCC cells, while KDM6B overexpression has the opposite effects. Mechanistically, KDM6B regulates TNFA_SIGNALING_VIA_NFκB signalling pathways, and H3K27me3 binds to the promoter region of C/EBPß, leading to the promotion of C/EBPß transcription. Besides, we show that GSK-J4, a chemical inhibitor of KDM6B, markedly inhibits proliferation and metastasis of ESCC cells. CONCLUSIONS: The present study demonstrated that KDM6B promotes ESCC progression by increasing the transcriptional activity of C/EBPß depending on its H3K27 demethylase activity.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Animais , Benzazepinas/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sequenciamento de Cromatina por Imunoprecipitação , Desmetilação do DNA , Conjuntos de Dados como Assunto , Progressão da Doença , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Histonas/metabolismo , Humanos , Histona Desmetilases com o Domínio Jumonji/antagonistas & inibidores , Histona Desmetilases com o Domínio Jumonji/genética , Masculino , Camundongos , Regiões Promotoras Genéticas , Pirimidinas/farmacologia , RNA-Seq , Ativação Transcricional , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Acta Pharmacol Sin ; 42(10): 1630-1641, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33495515

RESUMO

Respiratory syncytial virus (RSV) is leading cause of respiratory tract infections in early childhood. Gut microbiota is closely related with the pulmonary antiviral immunity. Recent evidence shows that gut dysbiosis is involved in the pathogenesis of RSV infection. Therefore; pharmacological and therapeutic strategies aiming to readjust the gut dysbiosis are increasingly important for the treatment of RSV infection. In this study, we evaluated the therapeutic effects of a probiotic mixture on RSV-infected mice. This probiotic mixture consisted of Lactobacillus rhamnosus GG, Escherichia coli Nissle 1917 and VSL#3 was orally administered to neonatal mice on a daily basis either for 1 week in advance or for 3 days starting from the day of RSV infection. We showed that administration of the probiotics protected against RSV-induced lung pathology by suppressing RSV infection and exerting an antiviral response via alveolar macrophage (AM)-derived IFN-ß. Furthermore, administration of the probiotics reversed gut dysbiosis and significantly increased the abundance of short-chain fatty acid (SCFA)-producing bacteria in RSV-infected mice, which consequently led to elevated serum SCFA levels. Moreover, administration of the probiotics restored lung microbiota in RSV-infected mice. We demonstrated that the increased production of IFN-ß in AMs was attributed to the increased acetate in circulation and the levels of Corynebacterium and Lactobacillus in lungs. In conclusion, we reveal that probiotics protect against RSV infection in neonatal mice through a microbiota-AM axis, suggesting that the probiotics may be a promising candidate to prevent and treat RSV infection, and deserve more research and development in future.


Assuntos
Antivirais/uso terapêutico , Microbioma Gastrointestinal/fisiologia , Macrófagos Alveolares/metabolismo , Probióticos/uso terapêutico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Animais , Disbiose/metabolismo , Ácidos Graxos Voláteis/metabolismo , Feminino , Interferon beta/metabolismo , Pulmão/metabolismo , Pulmão/microbiologia , Pulmão/patologia , Camundongos Endogâmicos BALB C , Vírus Sinciciais Respiratórios/patogenicidade
14.
Can J Infect Dis Med Microbiol ; 2021: 8518189, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777671

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is a disease caused by infection with the SFTS virus (SFTSV). SFTS has become a crucial public health concern because of the heavy burden, lack of vaccines, effective therapies, and high-fatality rate. Evidence suggests that SFTSV circulates between ticks and animals in nature and is transmitted to humans by tick bites. In particular, ticks have been implicated as vectors of SFTSV, where domestic or wild animals may play as the amplifying hosts. Many studies have identified antigens and antibodies against SFTSV in various animals such as sheep, goats, cattle, and rodents. Besides, person-to-person transmission through contact with blood or mucous of an infected person has also been reported. In this study, we reviewed the literature and summarized the vectors and hosts associated with SFTS and the possible risk factors.

15.
Bioorg Chem ; 99: 103813, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32334190

RESUMO

The chemical investigation of the fruits of a mangrove Sonneratia apetala collected from the Beibu Gulf led to the isolation of four new compounds, sonneradons A-D (1-4), as well as 18 known compounds (5-22). The structures of the new compounds were elucidated based on extensive spectroscopic analysis, and the structures of the known compounds were established by comparison of their spectroscopic data with those of related metabolites. The antiaging activities of all isolates were evaluated using the nematode Caenorhabditis elegans as a model organism. The results showed that 10 compounds could protect C. elegans by extending its lifespan. Compound 1 possessed the most potent effect in the anti-heat stress assay and significantly attenuated aging-related decreases in the pumping and bending of the nematodes in the healthspan assay. Molecular docking studies suggested that compound 1 was bound to the DNA binding domain of HSF-1 and promoted the conformation of HSF-1, thus strengthening the interaction between the HSF-1 and related DNA. GLN49, ASN-74, and LYS-80 of the binding region might be the key amino residues during the interaction.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Frutas/química , Lythraceae/química , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Caenorhabditis elegans/metabolismo , Relação Dose-Resposta a Droga , Simulação de Acoplamento Molecular , Estrutura Molecular , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Relação Estrutura-Atividade
16.
Bioorg Chem ; 99: 103820, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32283345

RESUMO

Seven pairs of new enantiomeric sesquiterpenoids, (+)/(-)-phaeocauline A - G [(+)/(-)-1-7], were isolated from the rhizomes of Curcuma phaeocaulis by chiral HPLC separation. Their structures, including absolute configurations, were determined by spectroscopic analyses and ECD data. The isolates were assessed for vasorelaxant, anti-platelet aggregative, and neuroprotective activities. Enantiomers (+)-1 and (-)-1 showed similar activity against abnormal platelet aggregation induced by arachidonic acid, while their C-4 epimers (+)-2 and (-)-2 were inactive, which indicated that those effects were stereoselective, but not enantioselective. Compounds (+)/(-)-3-5 exhibited vasorelaxant effects against KCl-induced contraction of rat aortic rings.


Assuntos
Aorta/efeitos dos fármacos , Curcuma/química , Fármacos Neuroprotetores/farmacologia , Cloreto de Potássio/antagonistas & inibidores , Sesquiterpenos/farmacologia , Animais , Aorta/metabolismo , Relação Dose-Resposta a Droga , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Agregação Plaquetária/efeitos dos fármacos , Cloreto de Potássio/farmacologia , Ratos , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Estereoisomerismo , Relação Estrutura-Atividade
17.
Sleep Breath ; 24(2): 745-750, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31853835

RESUMO

PURPOSE: We sought to unravel the role of hydrogen sulfide (H2S) in the development of hypertension in patients with obstructive sleep apnea (OSA). METHODS: The study sample included 80 patients with OSA and 45 healthy controls. All subjects underwent measurement of blood pressure (BP) and serum H2S level in the morning. Twentynine of the 39 patients with OSA and concomitant hypertension and 23 of the 41 patients with OSA but no concomitant hypertension received continuous positive alveolar pressure (CPAP) therapy for 4 weeks. Twenty-four-hour ambulatory BP and serum H2S were determined before and after CPAP. Respiratory indices including apnea hypopnea index (AHI), lowest oxygen saturation (SaO2), and length of time < 90% saturated (T90) were determined by polysomnography. RESULTS: Associations between H2S, BP, respiratory indices, and changes with CPAP were analyzed. OSA patients had significantly higher systolic BP (p = 0.003) and diastolic BP (p = 0.009) and lower H2S levels (p = 0.02) compared to healthy controls. H2S negatively correlated with AHI (p = 0.005), T90 (p = 0.009), morning systolic BP (p = 0.02), and morning diastolic BP (p = 0.03). All respiratory indices were significantly improved (p < 0.05) after CPAP in OSA patients with or without hypertension. BP was significantly reduced and H2S significantly increased after CPAP in OSA patients with hypertension (p < 0.05) but not in OSA patients without hypertension (p > 0.05). CONCLUSION: Multivariate linear regression analysis demonstrated that 24h systolic BP and 24h diastolic BP correlated with H2S as well as their changes after CPAP treatment. Reduction in H2S may play a role in the pathogenesis of hypertension in patients with OSA.


Assuntos
Sulfeto de Hidrogênio/sangue , Hipertensão/sangue , Apneia Obstrutiva do Sono/sangue , Adulto , Idoso , Associação , Pressão Sanguínea/fisiologia , Estudos de Casos e Controles , Pressão Positiva Contínua nas Vias Aéreas , Feminino , Seguimentos , Humanos , Hipertensão/epidemiologia , Hipertensão/terapia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polissonografia , Fatores de Risco , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/terapia
18.
Bioorg Chem ; 92: 103275, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31539747

RESUMO

A new seco-cadinane sesquiterpenoid (curcumane C, 1) and a pair of new nor-bisabolene enantiomers [(+)- and (-)-curcumane D, 2a and 2b] were isolated from C. longa. Compound 1 possesses an unusual 4,5-seco-cadinane skeleton with a tetrahydrophthalide moiety, while 2a and 2b contain an unusual 15-nor-bisabolene skeleton with a chromone core. All compounds exhibited significant vasorelaxant effects against KCl-induced contraction of rat aortic rings. Compound 1 also exhibited a vasorelaxant effect against phenylephrine-induced contraction of rat aortic rings. Meanwhile, compound 1 showed a stronger vasorelaxant effect in endothelium-intact rat aortic rings compared with endothelium-denuded rat aortic rings, indicating that vasodilation by 1 involved both endothelium-dependent and endothelium-independent pathways. Furthermore, compound 1 increased the NO content in human umbilical vein endothelial cells and its vasorelaxant effect could be attenuated by treatment with L-NAME, an endothelium NO synthase inhibitor. Thus, the underlying vasodilatory mechanisms of 1 may be mediated via abrogation of extracellular Ca2+ influx and regulation of NO release in vascular endothelial cells.


Assuntos
Aorta/efeitos dos fármacos , Curcuma/química , Sesquiterpenos/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Aorta/metabolismo , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio/metabolismo , Conformação Molecular , Fenilefrina/antagonistas & inibidores , Fenilefrina/farmacologia , Cloreto de Potássio/antagonistas & inibidores , Cloreto de Potássio/farmacologia , Ratos , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Estereoisomerismo , Relação Estrutura-Atividade , Vasodilatadores/química , Vasodilatadores/isolamento & purificação
19.
Molecules ; 24(22)2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31739601

RESUMO

Fuzi is a well-known traditional Chinese medicine developed from the lateral roots of Aconitum carmichaelii Debx. It is rich in alkaloids that display a wide variety of bioactivities, and it has a strong cardiotoxicity and neurotoxicity. In order to discriminate the geographical origin and evaluate the quality of this medicine, a method based on high-performance liquid chromatography (HPLC) was developed for multicomponent quantification and chemical fingerprint analysis. The measured results of 32 batches of Fuzi from three different regions were evaluated by chemometric analysis, including similarity analysis (SA), hierarchical cluster analysis (HCA), principal component analysis (PCA), and linear discriminant analysis (LDA). The content of six representative alkaloids of Fuzi (benzoylmesaconine, benzoylhypaconine, benzoylaconine, mesaconitine, hypaconitine, and aconitine) were varied by geographical origin, and the content ratios of the benzoylmesaconine/mesaconitine and diester-type/monoester-type diterpenoid alkaloids may be potential traits for classifying the geographical origin of the medicine. In the HPLC fingerprint similarity analysis, the Fuzi from Jiangyou, Sichuan, was distinguished from the Fuzi from Butuo, Sichuan, and the Fuzi from Yunnan. Based on the HCA and PCA analyses of the content of the six representative alkaloids, all of the batches were classified into two categories, which were closely related to the plants' geographical origins. The Fuzi samples from Jiangyou were placed into one category, while the Fuzi samples from Butuo and Yunnan were put into another category. The LDA analysis provided an efficient and satisfactory prediction model for differentiating the Fuzi samples from the above-mentioned three geographical origins. Thus, the content of the six representative alkaloids and the fingerprint similarity values were useful markers for differentiating the geographical origin of the Fuzi samples.


Assuntos
Aconitum/química , Alcaloides/química , Raízes de Plantas/química , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , Análise Discriminante , Análise de Componente Principal
20.
Can J Infect Dis Med Microbiol ; 2019: 4851914, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31341522

RESUMO

OBJECTIVES: High dependency on pesticides could cause selection pressure leading to the development of resistance. This study was conducted to assess the resistance of the house fly, Musca domestica, to five insecticides, namely, permethrin, deltamethrin, beta-cypermethrin, propoxur, and dichlorvos, in Zhejiang Province. METHODS: Field strains of house flies were collected from the 12 administrative districts in Zhejiang Province in 2011, 2014, and 2017, respectively. Topical application method was adopted for the bioassays. The probit analysis was used to determine the median lethal doses with the 95% confidence interval, and then the resistance ratio (RR) was calculated. The insecticides resistance in different years and the correlations of the resistance between different insecticides were also analyzed. RESULTS: The resistance of field strains house flies to insecticides in Zhejiang Province was relatively common, especially for permethrin, deltamethrin, and beta-cypermethrin. The reversion of the resistance to dichlorvos was found, and most of the field strains in Zhejiang Province became sensitive to dichlorvos in 2017. Propoxur was much easier to cause very high level of resistance; the Hangzhou strain had the highest RR value more than 1000 in 2014, and five field strains had the RR value more than 100 in 2017. Compared to 2011 and 2014, the resistance of the house flies to propoxur and deltamethrin increased significantly in 2017. The resistance of permethrin, deltamethrin, beta-cypermethrin, and propoxur was significantly correlated with each other, and the resistance of dichlorvos was significantly correlated with beta-cypermethrin. CONCLUSIONS: Our results suggested that resistance was existed in permethrin, deltamethrin, beta-cypermethrin, and propoxur in the house flies of Zhejiang Province, while the resistance reversion to dichlorvos was found.

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