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1.
J Biol Chem ; 300(8): 107543, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38992440

RESUMO

The pathogenesis of Parkinson's disease (PD) has been associated with mitochondrial dysfunction. Given that the PINK1/Parkin pathway governs mitochondrial quality control by inducing mitophagy to remove damaged mitochondria, therapeutic approaches to activate PINK1/Parkin-mediated mitophagy have the potential in the treatment of PD. Here, we have identified a new small molecule, BL-918, as an inducer of mitophagy via activating the PINK1/Parkin pathway. BL-918 triggers PINK1 accumulation and Parkin mitochondrial translocation to initiate PINK1/Parkin-mediated mitophagy. We found that mitochondrial membrane potential and mitochondrial permeability transition pore were involved in BL-918-induced PINK1/Parkin pathway activation. Moreover, we showed that BL-918 mitigated PD progression in MPTP-induced PD mice in a PINK1-dependent manner. Our results unravel a new activator of the PINK1/Parkin signaling pathway and provide a potential strategy for the treatment of PD and other diseases with dysfunctional mitochondria.


Assuntos
Mitocôndrias , Mitofagia , Doença de Parkinson , Proteínas Quinases , Transdução de Sinais , Ubiquitina-Proteína Ligases , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Proteínas Quinases/metabolismo , Proteínas Quinases/genética , Animais , Camundongos , Mitofagia/efeitos dos fármacos , Humanos , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Doença de Parkinson/genética , Mitocôndrias/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Masculino , Progressão da Doença , Fenilacetatos
2.
Plant Cell ; 34(7): 2688-2707, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35435234

RESUMO

Cambial development in the stems of perennial woody species is rigorously regulated by phytohormones. Auxin and gibberellin (GA) play crucial roles in stimulating cambial activity in poplar (Populus spp.). In this study, we show that the DELLA protein REPRESSOR of ga1-3 Like 1 (RGL1), AUXIN RESPONSE FACTOR 7 (ARF7), and Aux/INDOLE-3-ACETIC ACID 9 (IAA9) form a ternary complex that mediates crosstalk between the auxin and GA signaling pathways in poplar stems during cambial development. Biochemical analysis revealed that ARF7 physically interacts with RGL1 and IAA9 through distinct domains. The arf7 loss-of-function mutant showed markedly attenuated responses to auxin and GA, whereas transgenic poplar plants overexpressing ARF7 displayed strongly improved cambial activity. ARF7 directly binds to the promoter region of the cambial stem cell regulator WOX4 to modulate its expression, thus integrating auxin and GA signaling to regulate cambial activity. Furthermore, the direct activation of PIN-FORMED 1 expression by ARF7 in the RGL1-ARF7-IAA9 module increased GA-dependent cambial activity via polar auxin transport. Collectively, these findings reveal that the crosstalk between auxin and GA signaling mediated by the RGL1-ARF7-IAA9 module is crucial for the precise regulation of cambial development in poplar.


Assuntos
Proteínas de Arabidopsis , Populus , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Giberelinas/metabolismo , Ácidos Indolacéticos/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo
3.
J Neuroinflammation ; 21(1): 176, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026249

RESUMO

Accumulating evidence implicates that herpes simplex virus type 1 (HSV-1) has been linked to the development and progression of Alzheimer's disease (AD). HSV-1 infection induces ß-amyloid (Aß) deposition in vitro and in vivo, but the effect and precise mechanism remain elusive. Here, we show that HSV-1 infection of the brains of transgenic 5xFAD mice resulted in accelerated Aß deposition, gliosis, and cognitive dysfunction. We demonstrate that HSV-1 infection induced the recruitment of microglia to the viral core to trigger microglial phagocytosis of HSV-GFP-positive neuronal cells. In addition, we reveal that the NLRP3 inflammasome pathway induced by HSV-1 infection played a crucial role in Aß deposition and the progression of AD caused by HSV-1 infection. Blockade of the NLRP3 inflammasome signaling reduces Aß deposition and alleviates cognitive decline in 5xFAD mice after HSV-1 infection. Our findings support the notion that HSV-1 infection is a key factor in the etiology of AD, demonstrating that NLRP3 inflammasome activation functions in the interface of HSV-1 infection and Aß deposition in AD.


Assuntos
Doença de Alzheimer , Progressão da Doença , Herpesvirus Humano 1 , Camundongos Transgênicos , Microglia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Fagocitose , Transdução de Sinais , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/virologia , Camundongos , Microglia/metabolismo , Microglia/patologia , Microglia/virologia , Transdução de Sinais/fisiologia , Humanos , Herpes Simples/patologia , Herpes Simples/imunologia , Herpes Simples/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Modelos Animais de Doenças , Presenilina-1/genética , Presenilina-1/metabolismo
4.
J Transl Med ; 21(1): 492, 2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37480074

RESUMO

BACKGROUND: Diet may influence biological aging and the discrepancy (∆age) between a subject's biological age (BA) and chronological age (CA). We aimed to investigate the correlation of dietary flavonoids with the ∆age of organs (heart, kidney, liver) and the whole body. METHOD: A total of 3193 United States adults were extracted from the National Health and Nutrition Examination Survey (NHANES) in 2007-2008 and 2017-2018. Dietary flavonoids intake was assessed using 24-h dietary recall method. Multiple linear regression analysis was performed to evaluate the association of dietary flavonoids intake with the ∆age of organs (heart, kidney, liver) and the whole body. BA was computed based on circulating biomarkers, and the resulting ∆age was tested as an outcome in linear regression analysis. RESULTS: The ∆age of the whole body, heart, and liver was inversely associated with higher flavonoids intake (the whole body ∆age ß = - 0.58, cardiovascular ∆age ß = - 0.96, liver ∆age ß = - 3.19) after adjustment for variables. However, higher flavonoids intake positively related to renal ∆age (ß = 0.40) in participants with chronic kidney disease (CKD). Associations were influenced by population characteristics, such as age, health behavior, or chronic diseases. Anthocyanidins, isoflavones and flavones had the strongest inverse associations between the whole body ∆age and cardiovascular ∆age among all the flavonoids subclasses. CONCLUSION: Flavonoids intake positively contributes to delaying the biological aging process, especially in the heart, and liver organ, which may be beneficial for reducing the long-term risk of cardiovascular or liver disease.


Assuntos
Flavonoides , Coração , Adulto , Humanos , Inquéritos Nutricionais , Fígado , Envelhecimento
5.
Ecotoxicol Environ Saf ; 264: 115472, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37716072

RESUMO

Today, the existence of radio-frequency electromagnetic fields (RF-EMF) emitted from cell phones, wireless routers, base stations, and other sources are everywhere around our living environment, and the dose is increasing. RF-EMF have been reported to be cytotoxic and supposed to be a risk factor for various human diseases, thus, more attention is necessary. In recent years, interfere with mitochondrial calcium uptake by using mitochondrial calcium uniporter (MCU) inhibitor were suggested to be potential clinical treatment in mitochondrial calcium overload diseases, like neurodegeneration, ischemia/reperfusion injury, and cancer, but whether this approach increases the health risk of RF-EMF exposure are unknown. To address our concern, we did a preliminary study to determine whether inhibition of MCU will increase the genotoxicity of RF-EMF exposure in cells, and found that short-time (15 min) exposure to 1800 MHz RF-EMF induced significant DNA damage and cell apoptosis in mouse embryonic fibroblasts (MEFs) treated with Ruthenium 360 (Ru360), a specific inhibitor of MCU, but no significant effects on cell cycle, cell proliferation, or cell viability were observed. In conclusion, our results indicated that inhibiting MCU increases the genotoxicity of RF-EMF exposure, and more attention needs to be paid to the possible health impact of RF-EMF exposure under these treatments.


Assuntos
Cálcio , Rutênio , Animais , Camundongos , Humanos , Campos Eletromagnéticos/efeitos adversos , Fibroblastos , Dano ao DNA
6.
New Phytol ; 230(4): 1476-1488, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33540480

RESUMO

The regulation of cytokinin on secondary vascular development has been uncovered by modulating cytokinin content. However, it remains unclear how cytokinin enriched in developing secondary phloem regulates cambium activity in poplar. Here, we visualized the gradient distribution of cytokinin with a peak in the secondary phloem of poplar stem via immunohistochemical imaging, and determined the role of phloem-located cytokinin signaling during wood formation. We generated transgenic poplar harboring cytokinin oxidase/dehydrogenase (CKX)2, a gene encoding a cytokinin degrading enzyme, driven by the phloem-specific CLE41b promoter, indicating that the disruption of the cytokinin gradient pattern restricts the cambial activity. The RNA interference-based knockdown of the histidine kinase (HK) genes encoding cytokinin receptors specifically in secondary phloem significantly compromised the division activity of cambial cells, whereas the phloem-specific expression of a type-B response regulator (RR) transcription factor stimulated cambial proliferation, providing evidence for the noncell-autonomous regulation of local cytokinin signaling on the cambial activity. Moreover, the cambium-specific knockdown of HKs also led to restricted cambial activity, and the defects were aggravated by the reduced cytokinin accumulation. Our results showed that local cytokinin signaling in secondary phloem regulates cambial activity noncell-autonomously, and coordinately with its local signaling in cambium.


Assuntos
Câmbio , Populus , Câmbio/genética , Citocininas , Floema , Populus/genética , Transdução de Sinais
7.
New Phytol ; 230(5): 2011-2028, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33533479

RESUMO

For woody plants, clonal propagation efficiency is largely determined by adventitious root (AR) formation at the bases of stem cuttings. However, our understanding of the molecular mechanisms contributing to AR morphogenesis in trees remains limited, despite the importance of vegetative propagation, currently the most common practice for tree breeding and commercialization. Here, we identified Populus-specific miR476a as a regulator of wound-induced adventitious rooting that acts by orchestrating mitochondrial homeostasis. MiR476a exhibited inducible expression during AR formation and directly targeted several Restorer of Fertility like (RFL) genes encoding mitochondrion-localized pentatricopeptide repeat proteins. Genetic modification of miR476a-RFL expression revealed that miR476a/RFL-mediated dynamic regulation of mitochondrial homeostasis influences AR formation in poplar. Mitochondrial perturbation via exogenous application of a chemical inhibitor indicated that miR476a/RFL-directed AR formation depends on mitochondrial regulation that acts via auxin signaling. Our results thus establish a microRNA-directed mitochondrion-auxin signaling cascade required for AR development, providing insights into the role of mitochondrial regulation in the developmental plasticity of plants.


Assuntos
Populus , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Mitocôndrias , Melhoramento Vegetal , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Populus/genética
8.
New Phytol ; 227(3): 867-883, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32270484

RESUMO

Trichomes are specialized epidermal cells that contribute to plant resistance against herbivores. Their formation is controlled precisely by multiple genetic and environmental signals. Previous studies have shown that microRNA319 (miR319) and gibberellin (GA) signaling are involved in trichome development in Arabidopsis, but little is known about their interaction between these factors. Here we reported that the miR319a/TEOSINTE BRANCHED/CYCLOIDEA/PCF (TCP) module participates in trichome initiation synergistically with GA signaling in Populus tomentosa. We demonstrated that overexpression of miR319a decreased transcription levels of its targeted TCPs and significantly elevated leaf trichome density in transgenic poplar, resulting in decreasing insect herbivory. Conversely, repressing miR319a by short tandem target mimics (STTM) elevated TCP expression levels and decreased trichome density in transgenic plants. The trichome phenotype of 35S:miR319a plants could be abolished by introducing a miR319a-resistant form of TCP19. Furthermore, the miR319a-targeted TCP19 interacted directly with REPRESSOR OF ga1-3 (RGA), a downstream repressor of GA signaling. TCP19 and RGA synergistically inhibited the GLABROUS1 (GL1)-induced expression of trichome marker gene GLABRA2 (GL2), thereby repressing leaf trichome initiation. Our results provide an insight into the molecular mechanism by which miR319/TCP19 module and GA signaling coordinated regulating trichome initiation in P. tomentosa.


Assuntos
Proteínas de Arabidopsis , Populus , Animais , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Insetos/metabolismo , Populus/genética , Populus/metabolismo , Tricomas/metabolismo , Zea mays/metabolismo
9.
Cell Rep ; 42(3): 112185, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36857187

RESUMO

It is widely known that stimulator of interferon genes (STING) can trigger nuclear factor κB (NF-κB) signaling. However, whether and how the NF-κB pathway affects STING signaling remains largely unclear. Here, we report that Toll-like receptor (TLR)-, interleukin-1 receptor (IL-1R)-, tumor necrosis factor receptor (TNFR)-, growth factor receptor (GF-R)-, and protein kinase C (PKC)-mediated NF-κB signaling activation dramatically enhances STING-mediated immune responses. Mechanistically, we find that STING interacts with microtubules, which plays a crucial role in STING intracellular trafficking. We further uncover that activation of the canonical NF-κB pathway induces microtubule depolymerization, which inhibits STING trafficking to lysosomes for degradation. This leads to increased levels of activated STING that persist for a longer period of time. The synergy between NF-κB and STING triggers a cascade-amplified interferon response and robust host antiviral defense. In addition, we observe that several gain-of-function mutations of STING abolish the microtubule-STING interaction and cause abnormal STING trafficking and ligand-independent STING autoactivation. Collectively, our data demonstrate that NF-κB activation enhances STING signaling by regulating microtubule-mediated STING trafficking.


Assuntos
NF-kappa B , Transdução de Sinais , Interferons , NF-kappa B/metabolismo , Transdução de Sinais/genética , Receptores Toll-Like , Proteínas de Membrana
10.
Cancer Immunol Res ; 11(5): 583-599, 2023 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-36921097

RESUMO

Cyclic GMP-AMP (cGAMP) is a second messenger that activates the stimulator of interferon genes (STING) innate immune pathway to induce the expression of type I IFNs and other cytokines. Pharmacologic activation of STING is considered a potent therapeutic strategy in cancer. In this study, we used a cell-based phenotypic screen and identified podophyllotoxin (podofilox), a microtubule destabilizer, as a robust enhancer of the cGAMP-STING signaling pathway. We found that podofilox enhanced the cGAMP-mediated immune response by increasing STING-containing membrane puncta and the extent of STING oligomerization. Furthermore, podofilox changed the trafficking pattern of STING and delayed trafficking-mediated STING degradation. Importantly, the combination of cGAMP and podofilox had profound antitumor effects on mice by activating the immune response through host STING signaling. Together, these data provide insights into the regulation of cGAMP-STING pathway activation and demonstrate what we believe to be a novel approach for modulating this pathway and thereby promoting antitumor immunity.


Assuntos
Neoplasias , Podofilotoxina , Animais , Camundongos , Podofilotoxina/farmacologia , Proteínas de Membrana/metabolismo , Transdução de Sinais , Imunidade Inata
11.
Food Sci Nutr ; 11(7): 4233-4245, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37457170

RESUMO

The hard-shelled mussel (Mytilus coruscus) has been used as a traditional Chinese medicine and health food in China for centuries. Polysaccharides from mussel has been reported to have multiple biological functions, however, it remains unclear whether mussel polysaccharide (MP) exerts protective effects in intestinal functions, and the underlying mechanisms of action remain unclear. The aim of this study was to investigate the protective effects and mechanism of MP on intestinal oxidative injury in mice. In this study, 40 male BALB/C mice were used, with 30 utilized to produce an animal model of intestinal oxidative injury with intraperitoneal injection of cyclophosphamide (Cy) for four consecutive days. The protective effects of two different doses of MP (300 and 600 mg/kg) were assessed by investigating the change in body weight, visceral index, and observing colon histomorphology. Moreover, the underlying molecular mechanisms were investigated by measuring the antioxidant enzymes and related signaling molecules through ELISA, real-time PCR, and western blot methods. The results showed that MP pretreatment effectively protected the intestinal from Cy-induced injury: improved the colon tissue morphology and villus structure, increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, and reduced malondialdehyde (MDA) content in serum and colon tissues. Meanwhile, MP also significantly increased the expression levels of SOD, GSH-Px, heme oxygenase-1 (HO-1), and nuclear factor E2-related factor 2 (Nrf2) mRNA in colon tissues. Further, western blot results showed that the expression of Nrf2 protein was significantly upregulated while kelch-like ECH-associated protein 1 (Keap1) was significantly downregulated by MP in the colonic tissues. This study indicates that MP can ameliorate Cy-induced oxidative stress injury in mice, and Nrf2-Keap1 signaling pathway may mediate these protective effects.

12.
Front Psychol ; 13: 1014905, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36619066

RESUMO

Teaching for creativity (TfC) has received increasing attention as an important way to cultivate students' creative thinking and behaviors. The purpose of this study is to examine the mediating role of teachers' work engagement (WE) on the relationship between their emotional intelligence (EI) and teaching for creativity. The study is a cross-sectional design. The sample of the study is 3,307 secondary school English teachers working in Jilin Province, China. The findings show that the teachers' perceptions of emotional intelligence, work engagement and teaching for creativity are relatively high. The findings confirm the hypotheses. The results of structural equation modeling and bootstrapping show that teachers' emotional intelligence is positively correlated with work engagement and teaching for creativity, and teachers' work engagement mediates the relationship between emotional intelligence and teaching for creativity.

13.
Waste Manag ; 153: 167-177, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36099727

RESUMO

Flotation is an attractive method for separating the different components of waste printed circuit boards (WPCBs) due to its cleanliness and efficiency. Non-metallic particles (NMPs) with good floatability usually need to be floated, however, it is difficult to achieve complete removal. The effect of particle size on the flotation behavior of NMPs, which is usually ignored in previous studies, is concerned in this paper. Flotation tests and kinetic analysis were carried out to reveal the effect of reagent dosage on flotation characteristics of particles in narrow size fractions. As the fineness decreases, the particles are more likely to be floated. Equally, the finer the particle size, the lower the reagent dosage required to achieve the maximum recovery. For 1-0.5 mm and -0.045 mm, the maximum recovery increased from 42.16% (1500 g/t MIBC) to 97.31% (100 g/t MIBC). Therefore, the feasibility of reducing particle size by grinding to improve floatability was verified. The results show that the reduction of particle size can significantly promote its efficiency of being floated. After grinding treatment, -0.045 mm yields in each size fraction (1-0.5, 0.5-0.25, 0.25-0.125, 0.125-0.074, 0.074-0.045 mm) increased by 22.10%, 28.42%, 30.90%, 64.56%, 89.32%, resulting in an increase of 37.71%, 13.12%, 2.82%, 7.82% and 2.00% in maximum recovery, respectively. It is also proved that the particle size, rather than the resin content, has a more significant effect on the floatability of NMPs.


Assuntos
Resíduo Eletrônico , Resíduo Eletrônico/análise , Cinética , Metais , Tamanho da Partícula , Reciclagem
14.
Cell Rep ; 39(9): 110880, 2022 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-35649354

RESUMO

Cyclic 2',3'-GMP-AMP (cGAMP) binds to and activates stimulator of interferon genes (STING), which then induces interferons to drive immune responses against tumors and pathogens. Exogenous cGAMP produced by infected and malignant cells and synthetic cGAMP used in immunotherapy must traverse the cell membrane to activate STING in target cells. However, as an anionic hydrophilic molecule, cGAMP is not inherently membrane permeable. Here, we show that LL-37, a human host defense peptide, can function as a transporter of cGAMP. LL-37 specifically binds cGAMP and efficiently delivers cGAMP into target cells. cGAMP transferred by LL-37 activates robust interferon responses and host antiviral immunity in a STING-dependent manner. Furthermore, we report that LL-37 inducers vitamin D3 and sodium butyrate promote host immunity by enhancing endogenous LL-37 expression and its mediated cGAMP immune response. Collectively, our data uncover an essential role of LL-37 in innate immune activation and suggest new strategies for immunotherapy.


Assuntos
Fatores de Restrição Antivirais , Catelicidinas , Imunidade Inata , Interferons , Fatores de Restrição Antivirais/imunologia , Catelicidinas/imunologia , Humanos , Interferons/imunologia , Proteínas de Membrana/metabolismo , Nucleotídeos Cíclicos
15.
J Microbiol ; 58(8): 716-723, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32524342

RESUMO

Human cytomegalovirus (hCMV) is a ubiquitous herpesvirus, which results in the establishment of a latent infection that persists throughout the life of the host and can be reactivated when the immunity is low. Currently, there is no vaccine for hCMV infection, and the licensed antiviral drugs mainly target the viral enzymes and have obvious adverse reactions. Thus, it is important to search for compounds with anti-hCMV properties. The present study aimed to investigate the suppressive effects of piceatannol on hCMV Towne strain infection and the putative underlying mechanisms using human diploid fibroblast WI-38 cells. Piceatannol supplementation prevented the lytic changes induced by hCMV infection in WI-38 cells. Furthermore, piceatannol suppressed the expression of hCMV immediate-early (IE) and early (E) proteins as well as the replication of hCMV DNA in a dose-dependent manner. Moreover, hCMV-induced cellular senescence was suppressed by piceatannol, as shown by a decline in the senescence-associated ß-galactosidase (SA-ß-Gal) activity and decreased production of intracellular reactive oxygen species (ROS). p16INK4a, a major senescence-associated molecule, was dramatically elevated by current hCMV infection that was attenuated by pre-incubation with piceatannol in a dose-dependent manner. These results demonstrated that piceatannol suppressed the hCMV infection via inhibition of the activation of p16INK4a and cellular senescence induced by hCMV. Together, these findings indicate piceatannol as a novel and potent anti-hCMV agent with the potential to be developed as an effective treatment for chronic hCMV infection.


Assuntos
Antivirais/farmacologia , Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/efeitos dos fármacos , Estilbenos/farmacologia , Linhagem Celular , Senescência Celular/efeitos dos fármacos , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Citomegalovirus/genética , Citomegalovirus/crescimento & desenvolvimento , Reposicionamento de Medicamentos , Humanos , Proteínas Imediatamente Precoces/biossíntese , Espécies Reativas de Oxigênio/metabolismo , Replicação Viral/efeitos dos fármacos , beta-Galactosidase/metabolismo
16.
Zhongguo Zhong Yao Za Zhi ; 34(5): 583-6, 2009 Mar.
Artigo em Zh | MEDLINE | ID: mdl-19526789

RESUMO

OBJECTIVE: To develop an HPLC method for simultaneous determination of four major alkaloids in Lindera aggregate. METHOD: The analysis was carried out on an Agilent ZORBAX SB-C18 column (4.6 mm x 250 mm, 5 microm) with gradient elution using acetonitrile-water (containing 0. 15% diethylamine, adjusted to pH = 3.0 with acetic acid) as mobile phase. Flow rate was 1.0 mL x min(-1) and the detection wavelength was at 289 nm. RESULT: The calibration curves were linear over the range of 0.428-8.560 microg for boldine, 2.122-31.83 microg for norboldine, 0.760-15.20 microg for reticuline and 0.020 4-0.400 8 microg for linderegatine, respectively. The average recoveries were 99.18% for boldine, 101.0% for norboldine, 100.3% for reticuline and 99.17% for linderegatine, respectively. with RSD not more than 3.0%. CONCLUSION: The described method is reliable and convenient and could be used for the quality control of Lindera aggregate.


Assuntos
Alcaloides/análise , Cromatografia Líquida de Alta Pressão/métodos , Lindera/química
17.
Oxid Med Cell Longev ; 2019: 5276096, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612074

RESUMO

Calorie restriction (CR) is a nongenetic intervention with a robust effect on delaying aging in mammals and other organisms. A mild stimulation on mitochondrial biogenesis induced by CR seems to be an important action mode for its benefits. Here, we reported that a component isolated from Rhodiola rosea L., salidroside, delays replicative senescence in human fibroblasts, which is related to its stimulation on mitochondrial biogenesis by activating SIRT1 partly resulted from inhibition on miR-22. Salidroside increased the mitochondrial mass that accompanied an increment of the key regulators of mitochondrial biogenesis including PGC-1α, NRF-1, and TFAM and reversed the mitochondrial dysfunction in presenescent 50PD cells, showing a comparable effect to that of resveratrol. SIRT1 is involved in the inducement of mitochondrial biogenesis by salidroside. The declined expression of SIRT1 in 50PD cells compared with the young 30PD cells was prevented upon salidroside treatment. In addition, pretreatment of EX-527, a selective SIRT1 inhibitor, could block the increased mitochondrial mass and decreased ROS production induced by salidroside in 50PD cells, resulting in an accelerated cellular senescence. We further found that salidroside reversed the elevated miR-22 expression in presenescent cells according to a miRNA array analysis and a subsequent qPCR validation. Enforced miR-22 expression by using a Pre-miR-22 lentiviral construct induced the young fibroblasts (30PD) into a senescence state, accompanied with increased senescence-related molecules including p53, p21, p16, and decreased SIRT1 expression, a known target of miR-22. However, salidroside could partly impede the senescence progression induced by lenti-Pre-miR-22. Taken together, our data suggest that salidroside delays replicative senescence by stimulating mitochondrial biogenesis partly through a miR22/SIRT1 pathway, which enriches our current knowledge of a salidroside-mediated postpone senility effect and provides a new perspective on the antidecrepitude function of this naturally occurring compound in animals and humans.


Assuntos
Senescência Celular/efeitos dos fármacos , Glucosídeos/uso terapêutico , MicroRNAs/metabolismo , Mitocôndrias/metabolismo , Fenóis/uso terapêutico , Rhodiola/química , Glucosídeos/farmacologia , Humanos , Biogênese de Organelas , Fenóis/farmacologia
18.
Int J Biol Macromol ; 106: 1235-1239, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28860061

RESUMO

Porphyran sulfated galactan extracted from red algae Porphyra haitanensis is a sulfated polysaccharide, which possesses excellent activities. In the present study, WI-38 cells were treated with H2O2 to induce premature senescence and then the protection of porphyran against aging in vitro and associated molecular mechanisms were investigated. The protection occurred in a dose-dependent manner, offering an optimal efficacy starting at 10µg/mL. The proportion of SA-ß-gal positive cells in porphyran group decreases from 53% to 23% in the cultures at 30 PDs. Porphyran has been detected specifically reducing SAHF-like foci formation in senescent cells. In addition, porphyran significantly affected the p53-p21 pathways in H2O2-treated WI-38 cells. Our data suggest the promising role of porphyran as an attractive and bio-safe agent with the potential to retard senescence and attenuate senescence-related diseases.


Assuntos
Antioxidantes/química , Senescência Celular/efeitos dos fármacos , Galactanos/química , Polissacarídeos/química , Antioxidantes/uso terapêutico , Linhagem Celular , Galactanos/uso terapêutico , Humanos , Peróxido de Hidrogênio/toxicidade , Polissacarídeos/uso terapêutico , Porphyra/química , Sulfatos/química
19.
Environ Toxicol Pharmacol ; 58: 114-121, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29329019

RESUMO

Senescence is a complex multiple factor proces, which is still poorly understood. The purpose of this study was to find the proteome of cultured human fetal lung diploid fibroblasts (2BS) of different population doubling (PD), as well as the altered proteome induced by salidroside (SAL) in 2BS cells. Proteins were identified by two-dimensional electrophoresis (2-DE) combining matrix-assisted laser desorption/ionization-time and flight mass spectrometry (MAL DI-TOF/MS). As a result, we found 16 proteins with two-fold variations in senescent cells or after SAL treatment, some being reduced such as reticulocalbin-1, heat shock protein beta-6, elongation factor 1-delta, F-actin-capping protein subunit alpha-1, and chloride intracellular channel 1. In contrast, 40S ribosomal protein SA, proteasome subunit alpha type-5, and zinc finger BED domain-containing protein 5 increased with cell age. Furthermore, heat shock protein beta-6, Zinc finger BED domain-containing protein 5 was increased in PD30 cells after 10 µM SAL treatment, whereas, elongation factor 1-delta, 6-phosphogluconolactonase, Nucleoside diphosphate kinase A, F-actin-capping protein subunit alpha-1, Probable ATP-dependent RNA helicase DDX41, Chloride intracellular channel 1, and Peroxiredoxin-6 were increased in PD50 cells after 10 µM SAL treatment. Some of these proteins were involved in the protein synthetic and degradative pathways, which emphasizes the metabolic disorder or functional impairment of cell senescence. Moreover, these proteins could be candidate biomarkers for evaluating the SAL anti-senescence effect.


Assuntos
Senescência Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Glucosídeos/farmacologia , Fenóis/farmacologia , Proteoma/efeitos dos fármacos , Linhagem Celular , Diploide , Feto , Fibroblastos/metabolismo , Humanos , Pulmão/citologia , Proteoma/metabolismo , Proteômica
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