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1.
Front Plant Sci ; 15: 1399152, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828223

RESUMO

Lilium lancifolium Thunb (L. lancifolium) is an important medicinal and edible plant with outstanding functionality for selenium (Se) biofortification. However, the molecular response of L. lancifolium to exogenous Se has not been fully elucidated. In this study, the effects of different levels of Se on L. lancifolium growth and quality were explored by transcriptome, metabolome and biochemical analyses. The results showed that the total Se and organic Se content in L. lancifolium bulbs increased with increasing Se dosage (0-8.0 mmol/L). Moreover, Se stimulated the growth of L. lancifolium at low level (2.0 mmol/L) but showed an inhibitory effect at high levels (≥4.0 mmol/L). Metabolomic and biochemical analyses revealed that the bulb weight and the content of amino acid, soluble sugar, and soluble protein were significantly increased in the 2.0 mmol/L Se treatment compared with those in the control (0 mmol/L Se). Transcriptome and metabolome analyses revealed that the significant upregulation of the GPD1, GPAT and ADPRM genes promoted glycerophospholipid accumulation. Additionally, the significantly upregulated glyA and downregulated asnB, nadB, thrA and SAT genes coordinate to the regulation of amino acid biosynthesis. The significantly upregulated SUS, bgl B, BAM, and SGA1 genes were involved in soluble sugar accumulation under Se treatment. In summary, this study identified the optimal Se concentration (2.0 mmol/L), which significantly improved the growth and nutritional quality of L. lancifolium and contributed to understanding the combined effects of Se treatment on the expression of genes and the accumulation of metabolites in L. lancifolium bulbs.

3.
Acta Pharmacol Sin ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740904

RESUMO

The circadian clock is the inner rhythm of life activities and is controlled by a self-sustained and endogenous molecular clock, which maintains a ~ 24 h internal oscillation. As the core element of the circadian clock, BMAL1 is susceptible to degradation through the ubiquitin-proteasome system (UPS). Nevertheless, scant information is available regarding the UPS enzymes that intricately modulate both the stability and transcriptional activity of BMAL1, affecting the cellular circadian rhythm. In this work, we identify and validate UBR5 as a new E3 ubiquitin ligase that interacts with BMAL1 by using affinity purification, mass spectrometry, and biochemical experiments. UBR5 overexpression induced BMAL1 ubiquitination, leading to diminished stability and reduced protein level of BMAL1, thereby attenuating its transcriptional activity. Consistent with this, UBR5 knockdown increases the BMAL1 protein. Domain mapping discloses that the C-terminus of BMAL1 interacts with the N-terminal domains of UBR5. Similarly, cell-line-based experiments discover that HYD, the UBR5 homolog in Drosophila, could interact with and downregulate CYCLE, the BMAL1 homolog in Drosophila. PER2-luciferase bioluminescence real-time reporting assay in a mammalian cell line and behavioral experiments in Drosophila reveal that UBR5 or hyd knockdown significantly reduces the period of the circadian clock. Therefore, our work discovers a new ubiquitin ligase UBR5 that regulates BMAL1 stability and circadian rhythm and elucidates the underlying molecular mechanism. This work provides an additional layer of complexity to the regulatory network of the circadian clock at the post-translational modification level, offering potential insights into the modulation of the dysregulated circadian rhythm.

4.
Fitoterapia ; 169: 105567, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37315715

RESUMO

Eupatorium lindleyanum DC. has been used as a functional food in China for a long time. However, the antifibrotic activity of total sesquiterpenoids from Eupatorium lindleyanum DC. (TS-EL) is still unknown. In this study, we discovered that TS-EL reduced the increase in α-smooth muscle actin (α-SMA), type I collagen and fibronectin content, the formation of cell filaments and collagen gel contraction in transforming growth factor-ß1-stimulated human lung fibroblasts. Intriguingly, TS-EL did not change the phosphorylation of Smad2/3 and Erk1/2. TS-EL decreased the levels of serum response factor (SRF), a critical transcription factor of α-SMA, and SRF knockdown alleviated the transition of lung myofibroblasts. Furthermore, TS-EL significantly attenuated bleomycin (BLM)-induced lung pathology and collagen deposition and reduced the levels of two profibrotic markers, total lung hydroxyproline and α-SMA. TS-EL also decreased the levels of SRF protein expression in BLM-induced mice. These results suggested that TS-EL attenuates pulmonary fibrosis by inhibiting myofibroblast transition via the downregulation of SRF.


Assuntos
Eupatorium , Fibrose Pulmonar , Camundongos , Humanos , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Bleomicina/efeitos adversos , Bleomicina/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Estrutura Molecular , Pulmão , Fator de Crescimento Transformador beta1/efeitos adversos , Fator de Crescimento Transformador beta1/metabolismo , Fibroblastos , Colágeno/metabolismo , Diferenciação Celular , Camundongos Endogâmicos C57BL
5.
Altern Ther Health Med ; 29(5): 242-254, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37052973

RESUMO

Context: The Da-yuan-yin (DYY) decoction is a classical prescription of traditional Chinese medicine that has antipyretic and anti-inflammatory effects. Network Pharmacology (NP) is an emerging discipline based on system-biology theory and biosystem network analysis that researchers can use to predict drug-action targets and mechanisms. Objective: The study intended to use NP evaluate the protective effects of the fifth eluting fraction of the supernatant of the DYY decoction (DYY-5) for mice induced with acute lung injury (ALI) using lipopolysaccharide (LPS) and to explore DYY-5's mechanisms. Design: The research team performed an animal study. Setting: The study took place at the College of Pharmaceutical Science at Soochow University in Suzhou, China. Animals: The animals were 42 male Balb/c mice, about 20 to 25 g in weight. Intervention: The research team: instilled 2 mg/kg of LPS intratracheally (i.t.) to induce ALI. The team divided the mice into seven groups of six mice: (1) a control group; (2) a negative control group-the DYY-5 group with mice treated only with a high dosage, 60 mg/kg, of DYY-5 to investigate the effects of DYY-5 on normal mice; (3) the positive control group, the LPS group, with induced ALI but no treatments; (4) the LPS+60 mg/kg-DYY-5 group with induced ALI treated with a high dosage of DYY-5; (5) the LPS+30 mg/kg-DYY-5 group with induced ALI treated with a medium dosage of DYY-5; (6) the LPS+15 mg/kg-DYY-5 group with induced ALI treated with a low dosage of DYY-5; and (7) a reference drug control group, the LPS+DXM group, with induced ALI treated with 5 mg/kg of dexamethasone (DXM). Outcome Measures: The research team: (1) determined the chemical components of DYY; (2) identified the anticomplementary activities of DYY-5; (3) took lung specimens, serum, and bronchoalveolar lavage fluid (BALF) from the mice for histopathological examination, Western blot, and biochemical analysis; (4) measured total protein concentrations and lung W/D ratios; (5) measured the expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) using quantitative real-time polymerase chain reaction (PCR); (6) measured the levels of pro-inflammatory and anti-inflammatory factors, the activity of myeloperoxidase (MPO) and superoxide dismutase (SOD), and the levels of complements, including complements 3 (C3), C3c, C5a, C5aR1, and C5b-9, using kits; (7) analyzed the levels of nuclear factor-kappa B (NF-κB) and IkB kinase (IKK) using Western blot; and (8) used network pharmacology (NP) to predict DYY-5's mechanisms and potential targets. Results: The study's results were consistent with the NP analysis, which reflected the multitarget and multipathway characteristics of DYY-5 in alleviating ALI. The LPS+30 mg/kg-DYY-5 group had significantly lower lung wet-to-dry (W/D) ratios and total protein concentrations in BALF than the LPS group did, with P < .01 and P < .0001, respectively as did the LPS+60 mg/kg-DYY-5 group (both P < .0001). The 60 mg/kg of DYY-5 compared to the LPS group: (1) regulated the levels tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and interleukin-1 beta (IL-1ß), with all P < .0001, anti-inflammatory factors-IL-4 (P < .05), IL-10 (P < .001), and IL-13 (P < .001); (2) increased the activity of SOD (P < .0001) and decreased the activity of MPO (P < .0001) and the expressions of iNOS and COX-2 mRNA (both P < .01); (3) blocked the activation of NF-κB and IKK; and (4) alleviated the pathological changes in the lung tissue, by reducing the depositions of C3c and decreasing the levels of C3, C5a and C5aR1 (all P < .0001), C5b-9 (P < .001) and C3c (P < .01) in serum. Conclusions: The protective effects of DYY-5 on ALI were related to antioxidation, anti-complementary activities, and regulation of inflammatory factors through the IKK/NF-κB signal pathway. DYY-5 may be useful as a potential therapeutic agent for treating ALI in clinics.


Assuntos
Lesão Pulmonar Aguda , NF-kappa B , Masculino , Camundongos , Animais , NF-kappa B/genética , NF-kappa B/metabolismo , Lipopolissacarídeos , Ciclo-Oxigenase 2/efeitos adversos , Complexo de Ataque à Membrana do Sistema Complemento/efeitos adversos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Camundongos Endogâmicos BALB C , RNA Mensageiro , Superóxido Dismutase
6.
Life (Basel) ; 13(3)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36983920

RESUMO

The growth and development of Codonopsis tangshen, an important herb used in Chinese traditional medicine, have been seriously affected by continuous cropping obstacles. Therefore, understanding the molecular responses of C. tangshen to continuous cropping is imperative to improve its resistance to continuous cropping obstacles. Here, physiological and biochemical results showed that the levels of chlorophyll and malonaldehyde (MDA) were higher in the continuous cropping (LZ) group compared with those of the non-continuous cropping (FLZ) group, while superoxide dismutase (SOD) content was lower in the LZ group than in the FLZ group. Tandem mass tag (TMT)-based proteomic analysis was performed to investigate the response mechanism to continuous cropping obstacles in C. tangshen. A total of 70 differentially expressed proteins (DEPs) were significantly involved in relevant pathways, including photosynthesis, oxidative phosphorylation, ribosome activity, and secondary metabolites. The results suggest that these DEPs in C. tangshen might play a critical role in response to continuous cropping. These findings could provide scientific basis for improving C. tangshen's resistance to continuous cropping obstacles.

8.
Life (Basel) ; 13(1)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36676120

RESUMO

Codonopsis tangshen Oliv (C. tangshen) is a valuable traditional Chinese medicinal herb with tremendous health benefits. However, the growth and development of C. tangshen are seriously affected by high temperatures. Therefore, understanding the molecular responses of C. tangshen to high-temperature stress is imperative to improve its thermotolerance. Here, RNA-Seq analysis was performed to investigate the genome-wide transcriptional changes in C. tangshen in response to short-term heat stress. Heat stress significantly damages membrane stability and chlorophyll biosynthesis in C. tangshen, as evidenced by pronounced malonaldehyde (MDA), electrolyte leakage (EL), and reduced chlorophyll content. Transcriptome analysis showed that 2691 differentially expressed genes (DEGs) were identified, including 1809 upregulated and 882 downregulated. Functional annotations revealed that the DEGs were mainly related to heat shock proteins (HSPs), ROS-scavenging enzymes, calcium-dependent protein kinases (CDPK), HSP-HSP network, hormone signaling transduction pathway, and transcription factors such as bHLHs, bZIPs, MYBs, WRKYs, and NACs. These heat-responsive candidate genes and TFs could significantly regulate heat stress tolerance in C. tangshen. Overall, this study could provide new insights for understanding the underlying molecular mechanisms of thermotolerance in C. tangshen.

10.
Pharm Biol ; 61(1): 228-240, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36655330

RESUMO

CONTEXT: Da-Yuan-Yin is a Chinese traditional prescription. OBJECTIVE: This study explores the therapeutic effects of the Da-Yuan-Yin decoction polyphenol fraction (DYY-4) on acute lung injury (ALI) in mice induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: The mice (n = 10) were orally administrated with DYY-4 (15, 30, and 60 mg/kg) or DXM (5 mg/kg), half an hour after LPS (2 mg/kg) instilled intratracheally. The protein content and the levels of inflammatory factors, the levels of complements, the mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the level of myeloperoxidase (MPO) and superoxide dismutase (SOD), the expression of the IkB kinase (IKK) and nuclear factor-kappa B (NF-κB), the lung wet-to-dry weight (W/D) ratio and lung tissue were evaluated, 24 h after LPS challenge. Network pharmacology predicted potential targets. RESULTS: DYY-4 (30, 60 mg/kg, p < 0.01, p < 0.01) decreased the lung W/D ratio, total protein concentration, the levels of C3, C3c and C5a, the levels of TNF-α, IL-6, and IL-1ß, while increased the levels of IL-4 and IL-10. DYY-4 (60 mg/kg) decreased the levels of C5aR1, C5b-9 and COX-2 mRNA (p < 0.05), the levels of MPO and iNOS mRNA, the activation of the IKK/NF-κB pathway (p < 0.01), and increased the levels of IL-13 and SOD (p < 0.01). DYY-4 (60 mg/kg) relieved the lung tissue pathological changes and reduced the C3c deposition. DISCUSSION AND CONCLUSIONS: Network pharmacology combined with animal experiments revealed the targets of DYY-4 alleviating ALI.


Assuntos
Lesão Pulmonar Aguda , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Lipopolissacarídeos/toxicidade , Polifenóis/efeitos adversos , Ciclo-Oxigenase 2/genética , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/prevenção & controle , Pulmão , Superóxido Dismutase , RNA Mensageiro
11.
Plant Sci ; 328: 111568, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36528126

RESUMO

Michelia chapensis Dandy, a well-known medicinal woody plant endemic to China, is endangered and seriously constricted by seed dormancy-induced low-regeneration in natural conditions. Cold stratification can effectively reduce seed dormancy and promote the seed germination of M. chapensis. However, the molecular events and systematic changes that occurred during seed germination in M. chapensis remain largely unknown. In this study, we carried out transcriptomic and metabolomic analyses to elucidate the potential molecular mechanisms underlying seed germination in M. chapensis under cold stratification. The results showed that the embryo cells became bigger and looser with increasing stratification time. Moreover, the endosperm appeared reduced due to the consumption of nutrients. Seventeen phytohormones were examined by the metabolome targeted for hormones. Compared with the ES (no stratification), the levels of indole-3-acetic acid (IAA) and gibberellin A3 (GA3) were increased in the MS (stratification for 45 days), while the abscisic acid (ABA) was downregulated in both MS and LS (stratification for 90 days). The transcriptome profiling identified 24975 differentially expressed genes (DEGs) in the seeds during germination. The seed germination of M. chapensis was mainly regulated by the biological pathways of plant hormone signal transduction, energy supply, secondary metabolite biosynthesis, photosynthesis-related metabolism, and transcriptional regulation. This study reveals the biological evidence of seed germination at the transcriptional level and provides a foundation for unraveling molecular mechanisms regulating the seed germination of M. chapensis.


Assuntos
Magnoliaceae , Transcriptoma , Animais , Germinação/fisiologia , Espécies em Perigo de Extinção , Sementes/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Ácido Abscísico/metabolismo , Dormência de Plantas/fisiologia , Metaboloma , Magnoliaceae/genética , Magnoliaceae/metabolismo , Regulação da Expressão Gênica de Plantas
12.
Opt Express ; 30(25): 45970-45979, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36522989

RESUMO

Here, we report an all-fiber tunable ultrafast Raman laser synchronously pumped by a home-made 1.6 µm dissipative soliton (DS) picosecond (ps) laser, which produces Stokes light beyond 1.7 µm. The Raman gain medium is a segment of highly germanium-doped (Ge-doped) fiber offering a high Raman gain coefficient at the target wavelength. Once the Raman conversion cavity is synchronized with the pump light, a stable 1.7 µm Raman laser (the first Stokes light) can be obtained at a low pump threshold. The maximum output power of the 1.7 µm Raman laser can reach ∼ 22.62 mW. The wavelength tuning operation is independent of tunable pump source and intra-cavity filter. By adjusting the intra-cavity delay line simply, the different spectral component within the broad Raman gain bandwidth can be selectively synchronized with the pump light so that the Raman laser wavelength can be tuned continuously from 1702.6 nm ∼ 1728.84 nm. This tunable 1.7 µm waveband ultrafast laser will have potential applications in multiphoton microscopy for e.g. deep bio-imaging.

13.
Opt Express ; 30(18): 31806-31815, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36242255

RESUMO

A simple polymer twin-tube terahertz (THz) fiber that can be used as a polarization filter is proposed and investigated using the finite element method in this paper. The twin-tube THz fiber consists of two closely spaced identical tubes located symmetrically inside the protecting jacket. The simulation results show that the y-polarization fundamental mode (YPFM) can be well confined between the two tube walls near the fiber center, while the x-polarization fundamental mode (XPFM) has a huge confinement loss due to the coupling with the tube mode. For the fundamental mode (FM), a polarization extinction ratio (PER) of 30 dB can be realized after a 1.3 cm length of the fiber, and the insertion loss of the YPFM is less than 0.5 dB at 1 THz. In addition, higher order modes (HOMs) can be effectively suppressed by further increasing the fiber length. Simulation results indicate that all HOMs have powers being 30 dB lower than that of the supported YPFM after a 7.44 cm length of the fiber, and the insertion loss of the YPFM is less than 2.7 dB at 1 THz. Furthermore, the effects of fiber structure parameters on the loss properties are investigated, proving that the proposed fiber has a good fabrication tolerance. Owing to the simple structure, the proposed fiber polarization filter is easy to be fabricated and low-cost, which makes it a potential application in commercial THz systems.

14.
Front Plant Sci ; 13: 972804, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36035706

RESUMO

Codonopsis tangshen Oliv (C. tangshen) is an important Chinese traditional medicinal plant with various health benefits. However, the growth of C. tangshen are seriously affected by continuous cropping, which led to the decrease of the yield and quality. A field experiment was conducted to learn the effects of soil amendments on the growth of C. tangshen under continuous cropping condition, and the biological events which occurred at molecular level were investigated. The results indicated that the content of chlorophyll a (Chl a), chlorophyll b (Chl b), and carotenoid (Car) was significantly higher in SCPM (silicon-calcium-potassium-magnesium fertilizer), SCPMA (SCPM combined with azoxystrobin) and SCPMAOM (SCPM combined with azoxystrobin and organic manure) treatments. Moreover, the yield and the levels of alkaloid, polysaccharide, flavone and total protein in the treatments of SCPM, SCPMA and SCPMAOM were significantly higher than those in the control, and these indexes were all highest in the SCPMAOM treatment. RNA-sequencing (RNA-Seq) is an economical and efficient method to obtain genetic information for species with or without available genome data. In this study, RNA-Seq was performed to understand how continuously cropped C. tangshen responded to the soil amendments at the transcriptome level. The number of differentially expressed genes (DEGs) were as follows: CK vs. SCPM (719 up- and 1456 down-), CK vs. SCPMA (1302 up- and 1748 down-), CK vs. SCPMAOM (1274 up- and 1678 down-). The soil amendments affected the growth of C. tangshen mainly by regulating the genes involved in pathways of 'photosynthesis,' 'plant hormone signal transduction,' 'biosynthesis of unsaturated fatty acids,' 'phenylpropanoid biosynthesis,' and 'starch and sucrose metabolism,' etc. qRT-PCR was performed to validate the expressions of 10 target genes such as CP26, PsaF, and POX, etc., which verified the reliability of RNA-Seq results. Overall, this study revealed the roles and underlying mechanisms of the soil amendments in regulating the growth of continuously cropped C. tangshen at transcriptome level. These findings are beneficial for improving the continuous cropping tolerance and may be valuable for future genetic improvement of C. tangshen.

15.
Foods ; 11(13)2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35804737

RESUMO

The transmission spectrum of apples is affected by the fruit's size, which leads to poor prediction performance of the soluble solids content (SSC) models built for their different apple sizes. In this paper, three sets of near infrared (NIR) spectra of apples with various apple diameters were collected by applying NIR spectroscopy detection equipment to compare the spectra differences among various apple diameter groups. The NIR spectra of apples were corrected by studying the extinction rates within different apples. The corrected spectra were used to develop a partial least squares prediction model for their soluble solids content. Compared with the prediction model of the soluble solids content of apples without size correction, the Rp of PLSR improved from 0.769 to 0.869 and RMSEP declined from 0.990 to 0.721 in the small fruit diameter group; the Rp of PLSR improved from 0.787 to 0.932 and RMSEP declined from 0.878 to 0.531 in the large fruit diameter group. The proposed apple spectra correction method is effective and can be used to reduce the influence of sample diameter on NIR spectra.

16.
J Proteome Res ; 21(8): 2063-2070, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35820187

RESUMO

Kinases play important roles in cell signaling, and adenosine monophosphate (AMP) is known to modulate cellular energy homeostasis through AMP-activated protein kinase (AMPK). Here, we explored novel AMP-binding kinases by employing a desthiobiotin-conjugated AMP acyl-phosphate probe to enrich efficiently AMP-binding proteins. Together with a parallel-reaction monitoring-based targeted proteomic approach, we uncovered 195 candidate AMP-binding kinases. We also enriched desthiobiotin-labeled peptides from adenine nucleotide-binding sites of kinases and analyzed them using LC-MS/MS in the multiple-reaction monitoring mode, which resulted in the identification of 44 peptides derived from 43 kinases displaying comparable or better binding affinities toward AMP relative to adenosine triphosphate (ATP). Moreover, our proteomic data revealed a potential involvement of AMP in the MAPK pathway through binding directly to the relevant kinases, especially MEK2 and MEK3. Together, we revealed the AMP-binding capacities of a large number of kinases, and our work built a strong foundation for understanding how AMP functions as a second messenger to modulate cell signaling.


Assuntos
Proteoma , Proteômica , Proteínas Quinases Ativadas por AMP/metabolismo , Monofosfato de Adenosina , Trifosfato de Adenosina/metabolismo , Cromatografia Líquida , Peptídeos , Proteoma/genética , Espectrometria de Massas em Tandem
17.
Fitoterapia ; 156: 105100, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34921926

RESUMO

Eight new compounds (1-8), along with three known related compounds (9-11) were isolated from the leaves of Sauropus spatulifolius Beille. Their structures and configurations were elucidated by means of spectrometric and the modified Mosher's method. Among the new compounds, compounds 1 and 2 were identified as ethyl 3, 6-anhydro-2-deoxy-ß-D-arabino-hexofuranoside (1) and ethyl 3, 6-anhydro-2-deoxy- hexofuranoside (2). Compounds 3-5 were the 2-acetylpyrrole derivatives and identified as 2-(2-acetyl-1H-pyrrol-1-yl)-4-hydroxybutyric acid (3), methyl 4-(2-acetyl-lH-pyrrol- 1-yl) butanoate (4) and 1, 4-bis (2-acetyl-1H-pyrrol-1-yl) butane (5), respectively. Compound 6 was elucidated as 7-megastigmane-3, 8, 9-triol. Compounds 7, 8 were identified as kaempferol-3-O-2-deoxy-ß-D-glucoside (7) and kaempferol-3-O-ß-D- glucopyranosyl-(1-6)-2-deoxy-ß-D-glucoside (8). In addition, the cytotoxic activities of all the compounds were also evaluated, where compounds 3, 5, 7, 9\10 and 11 exhibited the magnificent inhibition activity on lung fibroblast differentiation induced by TGF-ß1with low toxicity against the RLE-6TN cell.


Assuntos
Flavonoides/isolamento & purificação , Glicosídeos/isolamento & purificação , Malpighiales/metabolismo , Extratos Vegetais/isolamento & purificação , Animais , Bioensaio , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Flavonoides/química , Flavonoides/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Humanos , Pulmão/citologia , Pulmão/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Malpighiales/química , Camundongos , Estrutura Molecular , Rotação Ocular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Folhas de Planta/metabolismo , Coelhos
18.
Toxicol Lett ; 352: 61-69, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34624459

RESUMO

Mitomycin treatment induces pulmonary toxicity, and alveolar epithelial cell senescence is crucial in the pathogenesis of the latter. However, the mechanism by which mitomycin induces alveolar epithelial cell senescence has yet to be elucidated. In this work, different doses (37.5-300 nM) of mitomycin induced the senescence of human alveolar type II-like epithelial cells and enhanced the phosphorylation of GSK3ß (S9). The GSK3ß (S9A) mutant reversed the senescence of mitomycin-treated alveolar epithelial cells. Pharmacological inhibition and gene deletion of Akt1, a kinase that regulates the phosphorylation of GSK3ß (S9), suppressed mitomycin-induced alveolar epithelial cell senescence. The knockdown of p53, a downstream effector of GSK3ß and an important regulator of cell senescence, repressed mitomycin-induced alveolar epithelial cell senescence. Treatment with baicalein weakened the phosphorylation of GSK3ß (S9) and alleviated the senescence of alveolar epithelial cells brought about by mitomycin treatment. GSK3ß (S9) phosphorylation appears to be the first signal involved in the mitomycin-induced senescence of alveolar epithelial cells and may present a potential target for attenuating mitomycin-induced pulmonary toxicity.


Assuntos
Alquilantes/toxicidade , Regulação para Baixo/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Mitomicina/toxicidade , Alvéolos Pulmonares/efeitos dos fármacos , Células A549 , Senescência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Flavanonas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/genética , Humanos , Imidazóis/farmacologia , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Alvéolos Pulmonares/citologia , Piridinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Bioorg Med Chem Lett ; 50: 128319, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34403728

RESUMO

Tigliane esters show many biological activities, including anti-HIV-1 activity. Our aim in this study was to establish structure-anti-HIV activity relationships for four series of tigliane-type diterpenoids. We synthesized and evaluated 29 new phorbol ester derivatives for anti-HIV activity and for cytotoxicity against human tumor cell lines. Among them, three derivatives, two phorbol-13-monoesters (5d and 5e) and a phorbol-12,13-diester (6a), showed significant anti-HIV activity. We found that better anti-HIV activity was often associated with a shorter acyl ester at C-13. Particularly, compounds with a phenyl ring in the ester side chain exhibited excellent anti-HIV activity and had good safety indexes. Due to its significant anti-HIV potency with a high selectivity index, phorbol-12,13-dicinnamoate (6a) was chosen as the potential candidate for further preclinical trials.


Assuntos
Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , HIV-1/fisiologia , Ésteres de Forbol/química , Ésteres de Forbol/farmacologia , Replicação Viral/efeitos dos fármacos , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
20.
Appl Opt ; 60(10): 2833-2838, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33798161

RESUMO

We present a linearly polarized single-longitudinal-mode (SLM) ytterbium-doped fiber laser with a polarization extinction ratio (PER) of over 35 dB and a narrow linewidth of less than 4.5 kHz. The very high PER is obtained by utilizing the polarization evolution effect at the optical fiber and the high-performance polarizing beam splitter. The SLM is achieved by using a segment of polarization-maintaining ytterbium-doped fiber as a narrowband filter. In addition, a high optical signal-to-noise ratio of 50 dB and a good slope efficiency of 60.5% are achieved. Using an ytterbium-doped fiber amplifier, a linearly polarized SLM laser system with a high power of over 2.5 W is demonstrated at 1064 nm.

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