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1.
Proc Natl Acad Sci U S A ; 121(7): e2322375121, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38315835

RESUMO

Protein S-acyl transferases (PATs) catalyze S-acylation, a reversible post-translational modification critical for membrane association, trafficking, and stability of substrate proteins. Many plant proteins are potentially S-acylated but few have corresponding PATs identified. By using genomic editing, confocal imaging, pharmacological, genetic, and biochemical assays, we demonstrate that three Arabidopsis class C PATs positively regulate BR signaling through S-acylation of BRASSINOSTEROID-SIGNALING KINASE1 (BSK1). PAT19, PAT20, and PAT22 associate with the plasma membrane (PM) and the trans-Golgi network/early endosome (TGN/EE). Functional loss of all three genes results in a plethora of defects, indicative of reduced BR signaling and rescued by enhanced BR signaling. PAT19, PAT20, and PAT22 interact with BSK1 and are critical for the S-acylation of BSK1, and for BR signaling. The PM abundance of BSK1 was reduced by functional loss of PAT19, PAT20, and PAT22 whereas abolished by its S-acylation-deficient point mutations, suggesting a key role of S-acylation in its PM targeting. Finally, an active BR analog induces vacuolar trafficking and degradation of PAT19, PAT20, or PAT22, suggesting that the S-acylation of BSK1 by the three PATs serves as a negative feedback module in BR signaling.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas Serina-Treonina Quinases , Acilação , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Brassinosteroides/metabolismo , Regulação da Expressão Gênica de Plantas , Transdução de Sinais , Transferases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo
2.
Acta Pharmacol Sin ; 45(1): 150-165, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37696989

RESUMO

Kidney fibrosis is the hallmark of chronic kidney disease (CKD) progression, whereas no effective anti-fibrotic therapies exist. Recent evidence has shown that tubular ferroptosis contributes to the pathogenesis of CKD with persistent proinflammatory and profibrotic responses. We previously reported that natural flavonol fisetin alleviated septic acute kidney injury and protected against hyperuricemic nephropathy in mice. In this study, we investigated the therapeutic effects of fisetin against fibrotic kidney disease and the underlying mechanisms. We established adenine diet-induced and unilateral ureteral obstruction (UUO)-induced CKD models in adult male mice. The two types of mice were administered fisetin (50 or 100 mg·kg-1·d-1, i.g.) for 3 weeks or 7 days, respectively. At the end of the experiments, the mice were euthanized, and blood and kidneys were gathered for analyzes. We showed that fisetin administration significantly ameliorated tubular injury, inflammation, and tubulointerstitial fibrosis in the two types of CKD mice. In mouse renal tubular epithelial (TCMK-1) cells, treatment with fisetin (20 µM) significantly suppressed adenine- or TGF-ß1-induced inflammatory responses and fibrogenesis, and improved cell viability. By quantitative real-time PCR analysis of ferroptosis-related genes, we demonstrated that fisetin treatment inhibited ferroptosis in the kidneys of CKD mice as well as in injured TCMK-1 cells, as evidenced by decreased ACSL4, COX2, and HMGB1, and increased GPX4. Fisetin treatment effectively restored ultrastructural abnormalities of mitochondrial morphology and restored the elevated iron, the reduced GSH and GSH/GSSG as well as the increased lipid peroxide MDA in the kidneys of CKD mice. Notably, abnormally high expression of the ferroptosis key marker ACSL4 was verified in the renal tubules of CKD patients (IgAN, MN, FSGS, LN, and DN) as well as adenine- or UUO-induced CKD mice, and in injured TCMK-1 cells. In adenine- and TGF-ß1-treated TCMK-1 cells, ACSL4 knockdown inhibited tubular ferroptosis, while ACSL4 overexpression blocked the anti-ferroptotic effect of fisetin and reversed the cytoprotective, anti-inflammatory, and anti-fibrotic effects of fisetin. In summary, we reveal a novel aspect of the nephroprotective effect of fisetin, i.e. inhibiting ACSL4-mediated tubular ferroptosis against fibrotic kidney diseases.


Assuntos
Ferroptose , Insuficiência Renal Crônica , Obstrução Ureteral , Humanos , Masculino , Camundongos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Rim/patologia , Flavonóis/uso terapêutico , Flavonóis/farmacologia , Obstrução Ureteral/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/patologia , Fibrose , Adenina/farmacologia
3.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1335-1342, 2024 Mar.
Artigo em Zh | MEDLINE | ID: mdl-38621981

RESUMO

This study aims to investigate the regulatory effect of the Spatholobi Caulis extract from ethyl acetate(SEA) on natural killer(NK) cells under physiological conditions and elucidate the underlying mechanism. The C57BL/6 mice were randomized into NC and SEA groups, and NK-92 cells were respectively treated with 0, 25, 50, and 100 µg·mL~(-1) SEA. The body weight and immune organ index of the mice were compared between groups. The lactate dehydrogenase(LDH) assay was employed to examine the cytotoxicity of NK-92 cells treated with SEA and the killing activity of mouse NK cells against YAC-1 cells. The cell-counting kit-8(CCK-8) was used to examine the impact of SEA on the proliferation of NK-92 cells. Flow cytometry was employed to measure the number of NK cells in the peripheral blood as well as the expression levels of natural killer group 2 member A(NKG2A) and natural killer group 2 member D(NKG2D). The enzyme-linked immunosorbent assay(ELISA) was performed to determine the interferon(IFN)-γ secretion in the serum. Semi-quantitative PCR was conducted to determine the mRNA levels of NKG2A, NKG2D, and IFN-γ in spleen cells. Western blot was employed to investigate the involvement of phosphoinositide 3-kinase(PI3K)/extracellular regulated protein kinase 1(ERK1) signaling pathway. The results showed that SEA exhibited no adverse effects on the body, while significantly enhance the number of NK cells and augment the cytotoxicity of NK-92 cells against YAC-1 cells. Moreover, it suppressed the expression of NKG2A, enhanced the expression of NKG2D, promoted IFN-γ secretion, and upregulated the protein levels of PI3K and ERK. The findings suggest that SEA has the potential to enhance the immune recognition and effector function of NK cells by increasing the cell number, modulating the expression of functional receptors, and promoting IFN-γ secretion via the PI3K/ERK signaling pathway.


Assuntos
Acetatos , Subfamília K de Receptores Semelhantes a Lectina de Células NK , Fosfatidilinositol 3-Quinases , Camundongos , Animais , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos Endogâmicos C57BL , Células Matadoras Naturais
4.
Neoplasma ; 70(1): 103-113, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36660796

RESUMO

Semaphorin 3A (Sema3A) has recently been proven to play an essential role in tumorigenesis. Here, the role of Sema3A in ovarian cancer is explored. The prognostic value of Sema3A was evaluated using the Kaplan-Meier plotter database, and stable expression cells were established by the delivery of lentivirus harboring SEMA3A cDNA or shRNA into OVCA433 and SKOV3 cells, respectively. Then CCK-8 assay, colony-formation assay, wound-healing assay, and Transwell assay were utilized to verify the effect of Sema3A on tumorigenesis. Co-cultures of ovarian cancer cells (OVCA433 and SKOV3) with a conditional medium collected from the established cells were further utilized to confirm the function of Sema3A. Then, the RNA-seq assay was adopted to explore the underlying mechanism. The results demonstrated that low expression of Sema3A was predictive of poor overall survival in patients with ovarian cancer. Functional experiments revealed that Sema3A inhibited proliferation, migration, and invasion in ovarian cancer cells. Secreted Sema3A in a conditioned culture medium also exhibited an anti-tumor effect in ovarian cancer cells. RNA-seq assay suggested that focal adhesion and Lin28B were involved in regulating Sema3A. Rescue assays further verified that Lin28B/ROCK1 axis was vital in the regulation of Sema3A and Lin28B significantly upregulated ROCK1 through let-7g microRNA. The presented data indicate that Sema3A inhibits proliferation and metastasis via the downregulation of Lin28B/ROCK1 in ovarian cancer.


Assuntos
Neoplasias Ovarianas , Proteínas de Ligação a RNA , Semaforina-3A , Feminino , Humanos , Carcinogênese , Proliferação de Células , Regulação para Baixo , MicroRNAs/genética , Neoplasias Ovarianas/genética , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Semaforina-3A/genética , Semaforina-3A/metabolismo
5.
Zhongguo Zhong Yao Za Zhi ; 48(1): 5-12, 2023 Jan.
Artigo em Zh | MEDLINE | ID: mdl-36725252

RESUMO

Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.


Assuntos
Esclerose Múltipla , Remielinização , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/patologia , Remielinização/fisiologia , Bainha de Mielina/patologia , Inflamação/tratamento farmacológico , Homeostase
6.
Zhongguo Zhong Yao Za Zhi ; 47(9): 2430-2439, 2022 May.
Artigo em Zh | MEDLINE | ID: mdl-35531690

RESUMO

A total of 15 batches of the substance reference of Guizhi Jia Gegen Decoction(GZGGD) were prepared and the characteristic fingerprints of them were established. Furthermore, the similarity of the fingerprints and peak attributes were explored. The extraction rate, and the content and the transfer rate ranges of the index components, puerarin, paeoniflorin, liquiritin, and ammonium glycyrrhizate were determined for the analysis of the quality value transfer. The result demonstrated that the fingerprints of the 15 batches of the samples showed high similarity(>0.99). A total of 15 characteristic peaks were identified from the fingerprints, with 10 for Puerariae Lobatae Radix, 1 for Cinnamomi Ramulus, 2 for Paeoniae Radix Alba, and 2 for Glycyrrhizae Radix et Rhizoma. The content of puerarin was 11.05-18.35 mg·g~(-1) and the average transfer rate was 21.27%-39.49%. The corresponding figures were 7.95-10.90 mg·g~(-1) and 23.28%-43.23% for paeoniflorin, 3.25-4.95 mg·g~(-1) and 32.31%-61.27% for ammonium glycyrrhizate, and 3.65-5.80 mg·g~(-1) and 14.57%-27.05% for liquiritin. The extraction rate of the 15 batches of samples was in the range of 16.85%-21.78%. In this paper, the quality value transfer of the substance reference of GZGGD was analyzed based on characteristic fingerprint, content of index components, and the extraction rate. This study is expected to lay a basis for the quality control and further development of GZGGD.


Assuntos
Compostos de Amônio , Medicamentos de Ervas Chinesas , Paeonia , Benchmarking , Cromatografia Líquida de Alta Pressão
7.
Geriatr Nurs ; 42(3): 772-775, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33906085

RESUMO

AIM: To investigate the needed, unneeded and unmet health care services among rural community-dwelling older adults in China and examine the influencing factors, aiming to facilitate the global development of the home care system for a healthier world. METHODS: This cross-sectional study investigated rural areas in three provinces in Western China. A total of 1727 rural community-dwelling older adults were enrolled. The needed, unneeded and unmet health care services were assessed by the Supply and Demand of Health Care Services (SD-HCS) questionnaire for older adults. RESULTS: Respect (73%, 1265/1727) was the most needed. The other top 9 needed mainly belonged to the divisions of health monitoring and information regarding chronic diseases. Re-employment or part-time jobs (71%, 1230/1727) was the most unneeded. All five protection and safety items were the most unmet but needed. Religion was the main influencing factor of those health care services that were less unmet but needed. CONCLUSIONS: Respect was basic for older adults, and chronic disease management was in great demand among rural community-dwelling older adults. Due to low willingness and the crisis workforce, a more flexible retirement policy is needed in rural China. It is urgent to improve the emergency care system in rural areas. Last but not least, more research is needed to explore the association between religion and health.


Assuntos
Serviços de Assistência Domiciliar , Vida Independente , Idoso , China , Estudos Transversais , Necessidades e Demandas de Serviços de Saúde , Humanos , População Rural
8.
Mol Plant Microbe Interact ; 33(7): 921-931, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32212906

RESUMO

Intrinsic disorder is a common structural characteristic of proteins and a central player in the biochemical processes of species. However, the role of intrinsic disorder in the evolution of plant-pathogen interactions is rarely investigated. Here, we explored the role of intrinsic disorder in the development of the pathogenicity in the RXLR AVR2 effector of Phytophthora infestans. We found AVR2 exhibited high nucleotide diversity generated by point mutation, early-termination, altered start codon, deletion/insertion, and intragenic recombination and is predicted to be an intrinsically disordered protein. AVR2 amino acid sequences conferring a virulent phenotype had a higher disorder tendency in both the N- and C-terminal regions compared with sequences conferring an avirulent phenotype. In addition, we also found virulent AVR2 mutants gained one or two short linear interaction motifs, the critical components of disordered proteins required for protein-protein interactions. Furthermore, virulent AVR2 mutants were predicted to be unstable and have a short protein half-life. Taken together, these results support the notion that intrinsic disorder is important for the effector function of pathogens and demonstrate that SLiM-mediated protein-protein interaction in the C-terminal effector domain might contribute greatly to the evasion of resistance-protein detection in P. infestans.


Assuntos
Proteínas Intrinsicamente Desordenadas/genética , Phytophthora infestans/genética , Doenças das Plantas/parasitologia , Sequência de Aminoácidos , Proteínas Intrinsicamente Desordenadas/química , Phytophthora infestans/patogenicidade , Virulência
9.
Int J Mol Sci ; 22(1)2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33379173

RESUMO

Acting as a typical harpin protein, Hpa1 of Xanthomonas oryzae pv. oryzae is one of the pathogenic factors in hosts and can elicit hypersensitive responses (HR) in non-hosts. To further explain the underlying mechanisms of its induced resistance, we studied the function of the most stable and shortest three heptads in the N-terminal coiled-coil domain of Hpa1, named N21Hpa1. Proteins isolated from N21-transgenic tobacco elicited HR in Xanthi tobacco, which was consistent with the results using N21 and full-length Hpa1 proteins expressed in Escherichia coli. N21-expressing tobacco plants showed enhanced resistance to tobacco mosaic virus (TMV) and Pectobacterium carotovora subsp. carotovora (Pcc). Spraying of a synthesized N21 peptide solution delayed the disease symptoms caused by Botrytis cinerea and Monilinia fructicola and promoted the growth and drought tolerance of plants. Further analysis indicated that N21 upregulated the expression of multiple plant defense-related genes, such as genes mediated by salicylic acid (SA), jasmonic acid (JA) and ethylene (ET) signaling, and genes related to reactive oxygen species (ROS) biosynthesis. Further, the bioavailability of N21 peptide was better than that of full-length Hpa1Xoo. Our studies support the broad application prospects of N21 peptide as a promising succedaneum to biopesticide Messenger or Illite or other biological pharmaceutical products, and provide a basis for further development of biopesticides using proteins with similar structures.


Assuntos
Proteínas de Bactérias/fisiologia , Agentes de Controle Biológico , Resistência à Doença/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Xanthomonas/genética , Ascomicetos , Botrytis , Pressão Osmótica , Pectobacterium , Nicotiana , Vírus do Mosaico do Tabaco , Água/fisiologia
10.
BMC Microbiol ; 19(1): 205, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477005

RESUMO

BACKGROUND: Cross-resistance, a phenomenon that a pathogen resists to one antimicrobial compound also resists to one or several other compounds, is one of major threats to human health and sustainable food production. It usually occurs among antimicrobial compounds sharing the mode of action. In this study, we determined the sensitivity profiles of Alternaria alternata, a fungal pathogen which can cause diseases in many crops to two fungicides (mancozeb and difenoconazole) with different mode of action using a large number of isolates (234) collected from seven potato fields across China. RESULTS: We found that pathogens could also develop cross resistance to fungicides with different modes of action as indicated by a strong positive correlation between mancozeb and difenoconazole tolerances to A. alternata. We also found a positive association between mancozeb tolerance and aggressiveness of A. alternata, suggesting no fitness penalty of developing mancozeb resistance in the pathogen and hypothesize that mechanisms such as antimicrobial compound efflux and detoxification that limit intercellular accumulation of natural/synthetic chemicals in pathogens might account for the cross-resistance and the positive association between pathogen aggressiveness and mancozeb tolerance. CONCLUSIONS: The detection of cross-resistance among different classes of fungicides suggests that the mode of action alone may not be an adequate sole criterion to determine what components to use in the mixture and/or rotation of fungicides in agricultural and medical sects. Similarly, the observation of a positive association between the pathogen's aggressiveness and tolerance to mancozeb suggests that intensive application of site non-specific fungicides might simultaneously lead to reduced fungicide resistance and enhanced ability to cause diseases in pathogen populations, thereby posing a greater threat to agricultural production and human health. In this case, the use of evolutionary principles in closely monitoring populations and the use of appropriate fungicide applications are important for effective use of the fungicides and durable infectious disease management.


Assuntos
Alternaria/efeitos dos fármacos , Farmacorresistência Fúngica , Fungicidas Industriais/farmacologia , Alternaria/genética , Alternaria/isolamento & purificação , Alternaria/fisiologia , China , Dioxolanos/farmacologia , Maneb/farmacologia , Doenças das Plantas/microbiologia , Solanum tuberosum/microbiologia , Triazóis/farmacologia , Zineb/farmacologia
11.
BMC Complement Altern Med ; 19(1): 271, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31627724

RESUMO

BACKGROUND: Plant secondary metabolites and phytochemicals that exhibit strong bioactivities have potential to be developed as safe and efficient natural antimicrobials against food contamination and addressing antimicrobial resistance caused by the overuse of chemical synthetic preservative. In this study, the chemical composition, antibacterial activities and related mechanism of the extracts of the valonia and the shell of Quercus variabilis Blume were studied to determine its potential as a safe and efficient natural antimicrobial. METHODS: The phenolic compositions of valonia and shell extracts were determined by folin-ciocalteau colourimetric method, sodium borohydride/chloranil-based assay and the aluminium chloride method and then further identified by the reverse-phase HPLC analysis. The antibacterial activities of valonia and shell extracts were evaluated by the agar disk diffusion method and agar dilution method. The related antibacterial mechanism was explored successively by the membrane of pathogens effect, phosphorous metabolism, whole-cell proteins and the microbial morphology under scanning electron microscopy. RESULTS: The n-butanol fraction and water fraction of valonia along with n-butanol fraction of the shell contains enrich phenolics including ellagic acid, theophylline, caffeic acid and tannin acid. The n-butanol fraction and ethanol crude extracts of valonia exhibited strong antibacterial activities against Salmonella paratyphi A (S. paratyphi A) and Staphylococcus aureus (S. aureus) with the DIZ values ranged from 10.89 ± 0.12 to 15.92 ± 0.44, which were greater than that of the Punica granatum (DIZ: 10.22 ± 0.18 and 10.30 ± 0.21). The MIC values of the n-butanol fraction and ethanol crude extracts of valonia against S. paratyphi A and S. aureus were 1.25 mg/ml and 0.625 mg/ml. The related antibacterial mechanism of n-butanol fraction and ethanol crude extracts of valonia may be attributed to their strong impact on membrane permeability and cellular metabolism. Those extracts exhibited strong antibacterial activity according to inhibit the synthesis of bacterial proteins and seriously change morphological structure of bacterial cells. CONCLUSIONS: The n-butanol fraction and ethanol crude extracts of valonia had reasonably good antibacterial activities against S. paratyphi A and S. aureus. This study suggests possible application of valonia and shell as natural antimicrobials or preservatives for food and medical application.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Quercus/química , Salmonella paratyphi A/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Nozes/química , Extratos Vegetais/isolamento & purificação , Salmonella paratyphi A/crescimento & desenvolvimento , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/crescimento & desenvolvimento
12.
Mikrochim Acta ; 185(10): 483, 2018 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-30269212

RESUMO

The authors report on a one-pot approach for synthesizing highly fluorescent protamine-stabilized gold nanoclusters. These are shown to be a viable nanoprobe for selective and sensitive fluorometric determination of lead(II) via quenching of fluorescence via Pb(II)-Au(I) interaction. Under optimized conditions, fluorescence measured at excitation/emission peaks of 300/599 nm drops in the 80 nM-15 µM lead(II) concentration range. The detection limit is 24 nM, and relative standard deviations (for n = 11) at concentrations of 0.10, 4.0 and 15 µM are 1.6, 2.5 and 1.9%, respectively. The relative recoveries of added lead(II) in the water samples ranged from 97.9 ± 2.29% to 101.2 ± 1.83%. Graphical abstract Lead(II) ions are found to be able to selectively and sensitively quench the fluorescence of the protamine-gold nanoclusters (PRT-AuNCs). Thereby, an inexpensive, selective and sensitive lead(II) assay was established.

13.
Zhonghua Nan Ke Xue ; 24(1): 19-26, 2018.
Artigo em Zh | MEDLINE | ID: mdl-30157355

RESUMO

OBJECTIVE: To explore the change in the proliferation of spermatogenic cells in the male mouse with infertility induced by exogenous estradiol benzoate (EB). METHODS: Sixty male mice aged 4 weeks were randomly divided into a control, a low-dose EB, and a high-dose EB group to be injected intramuscularly with corn oil at 150 µl or EB at 5 or 10 mg/kg, respectively, every other day for 4 weeks. Then, we obtained the weight and indexes of the testis, performed HE staining of the paraffin sections of the testis tissue and epididymal cauda, counted the spermatozoa in the epididymal sperm suspension, and determined the expression of the proliferating cell nuclear antigen (PCNA), the mRNA expressions of CyclinA1, CyclinB1, VASA and p53, and the protein expressions of p53 and phosphorylated p53 in the testis by immunohistochemistry, qRT-PCR and Western blot, respectively. RESULTS: In comparison with the controls, the mice treated with EB showed significantly decreased testicular indexes (P <0.05), no sperm in the sperm suspension or epididymal tubes, remarkably reduced numbers of spermatogonia, primary spermatocytes and Sertoli cells (P <0.05), down-regulated expression of PCNA (P <0.05) and mRNA expressions of CyclinA1, CyclinB1, PCNA and VASA in the seminiferous tubules (P <0.05), but a dose-dependent increase of the p53 level (P <0.05). Western blot revealed markedly higher levels of p53 protein expression and phosphorylation in the EB than in the control group (P <0.05) and even higher in the 10 mg/kg than in the 5 mg/kg EB group (P <0.05). CONCLUSIONS: EB inhibited the proliferation of spermatogenic cells by down-regulating the expressions of cell cycle-related factors in a dose-dependent manner, which might contribute to abnormal proliferation of spermatogenic cells in the testis of infertile male mice.


Assuntos
Proliferação de Células/efeitos dos fármacos , Anticoncepcionais/farmacologia , Estradiol/análogos & derivados , Infertilidade Masculina/patologia , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Proliferação de Células/fisiologia , Anticoncepcionais/administração & dosagem , Ciclina A1/metabolismo , Ciclina B1/metabolismo , RNA Helicases DEAD-box/metabolismo , Relação Dose-Resposta a Droga , Regulação para Baixo , Epididimo/citologia , Epididimo/efeitos dos fármacos , Estradiol/administração & dosagem , Estradiol/farmacologia , Masculino , Camundongos , Antígeno Nuclear de Célula em Proliferação/metabolismo , RNA Mensageiro/metabolismo , Distribuição Aleatória , Túbulos Seminíferos/citologia , Túbulos Seminíferos/efeitos dos fármacos , Células de Sertoli/citologia , Células de Sertoli/efeitos dos fármacos , Contagem de Espermatozoides , Espermatócitos/citologia , Espermatócitos/efeitos dos fármacos , Espermatogônias/citologia , Espermatogônias/efeitos dos fármacos , Espermatozoides/citologia , Testículo/citologia , Testículo/metabolismo , Proteína Supressora de Tumor p53/metabolismo
14.
Int J Neurosci ; 127(4): 334-338, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27788616

RESUMO

OBJECTIVES: Little is known about patients with neuromyelitis optica spectrum disorders (NMOSD) as defined by onset age. This study aimed to analyze the different demographic, clinical, laboratory, and magnetic resonance imaging (MRI) characteristics in early-onset (≤50 years) NMOSD (EONMOSD) and late-onset (>50 years) NMOSD (LONMOSD). MATERIALS AND METHODS: We enrolled 142 patients with NMOSD from Tianjin Medical University General Hospital, Tianjin, China, and categorized them into two groups according to the age of onset: EONMOSD and LONMOSD. Demographic, clinical, laboratory, and MRI characteristics were collected and compared between the two groups. Serum aquaporin-4 (AQP4) antibody levels were determined by cell-based assay and fluorescence immunoprecipitation assays. RESULTS: Among the patients studied, 83 had early onset (≤50 years) and 59 had late onset (>50 years) of NMOSD. As compared with LONMOSD, EONMOSD patients had more severe visual disability according to functional scores in clinical parameters, significantly lower C3 and C4 serum levels, more frequent cervical lesions, and more lesions around the fourth ventricle, but fewer lesions in hemispheric white matter. LONMOSD patients suffered more motor and sensory disability than EONMOSD patients. CONCLUSIONS: In NMOSD, the clinical, laboratory, and MRI features differ according to age of onset, suggesting that differences in pathogenesis and treatment should be further investigated.


Assuntos
Neuromielite Óptica/epidemiologia , Adolescente , Adulto , Fatores Etários , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Anticorpos/sangue , Aquaporina 4/imunologia , Avaliação da Deficiência , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/sangue , Adulto Jovem
15.
Mol Ecol ; 25(16): 4047-58, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27288627

RESUMO

Temperature is one of the most important environmental parameters with crucial impacts on nearly all biological processes. Due to anthropogenic activity, average air temperatures are expected to increase by a few degrees in coming decades, accompanied by an increased occurrence of extreme temperature events. Such global trends are likely to have various major impacts on human society through their influence on natural ecosystems, food production and biotic interactions, including diseases. In this study, we used a combination of statistical genetics, experimental evolution and common garden experiments to investigate the evolutionary potential for thermal adaptation in the potato late blight pathogen, Phytophthora infestans, and infer its likely response to changing temperatures. We found a trade-off associated with thermal adaptation to heterogeneous environments in P. infestans, with the degree of the trade-off peaking approximately at the pathogen's optimum growth temperature. A genetic trade-off in thermal adaptation was also evidenced by the negative association between a strain's growth rate and its thermal range for growth, and warm climates selecting for a low pathogen growth rate. We also found a mirror effect of phenotypic plasticity and genetic adaptation on growth rate. At below the optimum, phenotypic plasticity enhances pathogen's growth rate but nature selects for slower growing genotypes when temperature increases. At above the optimum, phenotypic plasticity reduces pathogen's growth rate but natural selection favours for faster growing genotypes when temperature increases further. We conclude from these findings that the growth rate of P. infestans will only be marginally affected by global warming.


Assuntos
Adaptação Biológica/genética , Phytophthora infestans/genética , Solanum tuberosum/microbiologia , Temperatura , Genótipo , Fenótipo , Seleção Genética
16.
Environ Monit Assess ; 188(12): 675, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27853967

RESUMO

The aims of this experiment are to explore the accumulation of metal contamination of different varieties of rice planted in paddy fields and to provide a basis for the further research. The rice specimens were grown in and collected from a total area of 8.24 acres of rice planting fields where local farmers cultivated 50 different kinds of rice. The crops were grown using the methods of seedling, transplanting, fertilizing, and irrigation, under the guidance of professional and technical personnel. The 50 kinds of paddy rice contain 20 kinds of conventional rice, 15 kinds of two-line hybrid rice, 15 kinds of three-line hybrid rice, and the whole experiment lasted 100 days. To begin our analysis of the data, we first gathered 15 irrigation water samples respectively from the first day of the experiment. This was then followed by gathering water samples from the tillering stage, then the development stage, the solid phase, and finally, the last day of the experiment. On the first day and at the end of the experiment, we had respectively gathered 6 mud samples from the rice paddies, with a total 12 parts of it. In addition to this, by the end of the experiment, we had gathered 6 samples of rice spike from each type of the investigated rice, with a total 300 parts of it. These samples were then analyzed in the laboratory to detect the contents and amounts of lead, cadmium, chromium, arsenic, copper, calcium, fluoride, nitrogen, phosphorus, potassium in the samples, and the pH quality of the samples. The quality of irrigation water was evaluated according to irrigation water quality standards (GB 5084-2005); the rice paddy mud samples were detected and evaluated respectively according to farmland soil environment quality monitor technology standards (NY/T 395-2012) and the journal of environmental quality assessment standard of edible agricultural products (HJ 332-2006); the rice grains were detected and evaluated according to the limited food standards (GB 2762-2012); the bioaccumulation factors (BCFs) were adopted to evaluate the accumulation ability of metal contamination in rice. As a result, the test values of the irrigation water samples were within irrigation water quality standards. Only the content of cadmium was beyond the environmental quality assessment standard of edible agricultural products, by 0.07 mg/kg. The content of lead and cadmium in 50 different rice were 0.41 ± 0.01~0.49 ± 0.01 mg/kg and 0.22 ± 0.01~0.25 ± 0.01 mg/kg, respectively. The varietal differences were not statistically significant (P>0.05). Lead BCFs, cadmium BCFs, and chromium BCFs in 50 different kinds of rice had no statistical difference (P>0.05). For the content of lead, cadmium, chromium, inorganic arsenic and copper in the conventional rice samples, two-line hybrid rice samples, and three-line hybrid rice samples, there was no statistical difference (P>0.05). Lead BCFs, cadmium BCFs, chromium BCFs, arsenic BCFs, and copper BCFs also had no statistical difference (P>0.05). This means the content of cadmium and lead contaminant in the 50 kinds of rice exceeded food quality and limits. The content of cadmium of mud samples exceeded the assessment standard by 0.07 mg/kg, the content of cadmium, of the 50 kinds of rice, exceeded the limited food standard by 0.04 mg/kg. The content of lead in the paddy mud was within the limited value, but the content of lead exceeded the limited food standard by 0.24 mg/kg. For the lead BCFs, cadmium BCFs, and chromium BCFs of the 50 kinds of rice, there was no statistically significant difference. This was the same for lead BCFs, cadmium BCFs, chromium BCFs, arsenic BCFs, and copper BCFs during conventional rice, two-line hybrid rice, and three-line hybrid rice. For the above, the rice had a strong adsorption capacity of lead. The conclusions of this data lead us to not only implement measures of control but also to conduct research on the suitable levels of lead in edible agricultural products.


Assuntos
Metais Pesados/metabolismo , Oryza/metabolismo , Poluentes do Solo/metabolismo , Monitoramento Ambiental , Contaminação de Alimentos/análise , Metais Pesados/química , Oryza/química , Poluentes do Solo/química
17.
Cancer Cell Int ; 15(1): 9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25685065

RESUMO

BACKGROUND: Recepteur d'origine nantais (RON) is a receptor tyrosine kinase whose overexpression has been observed in human gastric cancers. This study aimed to determine whether overexpression of the variant RONΔ160 could induce tumorigenicity of gastric cancer cells in vitro or in vivo, and whether its specific small molecule inhibitor (Compound I) could inhibit the effect of RONΔ160. METHODS: We constructed human gastric cancer cell line MGC-803 that was stably transfected with a recombinant plasmid expressing RONΔ160, and the effect of RONΔ160 overexpression and macrophage-stimulating protein (MSP) activation on proliferation, migration and invasion abilities of MGC-803 cells were evaluated. Tumor-bearing mice with gastric cancer cells were used to analyze the effects of RONΔ160 overexpression and Compound I on implanted tumor growth. RESULTS: In vitro, overexpression of RONΔ160 in MGC-803 cells resulted changes to their cell morphology, and promoted cell proliferation, migration and invasion. In addition, overexpression of RONΔ160 increased the proportion of cells in the S phase. The effect of RONΔ160 was significantly enhanced by induction of MSP inducing (p < 0.05). In vivo, RONΔ160 promoted the growth of MGC-803 cells in nude mice, including increased tumor size and weight, and lower tumor incubation period. The Compound I inhibited the tumorigenic abilities of RONΔ160 (p <0.05). CONCLUSIONS: The results indicate that overexpression of the variant RONΔ160 altered the phenotype and tumorigenicity of MGC-803 cells. Its specific small molecule inhibitor could inhibit the effect of RONΔ160. Therefore, the variant RONΔ160 may become a potential therapeutic target for gastric cancer.

18.
Chemphyschem ; 16(3): 601-6, 2015 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-25511660

RESUMO

A series of metal-free organic dyes with electron-rich (D) and electron-deficient units (A) as π linkers have been studied theoretically by means of density functional theory (DFT) and time-dependent DFT calculations to explore the effects of π spacers on the optical and electronic properties of triphenylamine dyes. The results show that Dye 1 with a structure of D-A-A-A is superior to the typical C218 dye in various key aspects, including the maximum absorption (λmax =511 nm), the charge-transfer characteristics (D/Δq/t is 5.49 Å/0.818 e(-) /4.41 Å), the driving force for charge-carrier injection (ΔGinject =1.35 eV)/dye regeneration (ΔGregen =0.27 eV), and the lifetime of the first excited state (τ=3.1 ns). It is thus proposed to be a promising candidate in dye-sensitized solar cell applications.

19.
Mol Cell Proteomics ; 12(10): 2804-19, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23824909

RESUMO

Bcl2-associated athanogene 3 (BAG3), a member of the BAG family of co-chaperones, plays a critical role in regulating apoptosis, development, cell motility, autophagy, and tumor metastasis and in mediating cell adaptive responses to stressful stimuli. BAG3 carries a BAG domain, a WW domain, and a proline-rich repeat (PXXP), all of which mediate binding to different partners. To elucidate BAG3's interaction network at the molecular level, we employed quantitative immunoprecipitation combined with knockdown and human proteome microarrays to comprehensively profile the BAG3 interactome in humans. We identified a total of 382 BAG3-interacting proteins with diverse functions, including transferase activity, nucleic acid binding, transcription factors, proteases, and chaperones, suggesting that BAG3 is a critical regulator of diverse cellular functions. In addition, we characterized interactions between BAG3 and some of its newly identified partners in greater detail. In particular, bioinformatic analysis revealed that the BAG3 interactome is strongly enriched in proteins functioning within the proteasome-ubiquitination process and that compose the proteasome complex itself, suggesting that a critical biological function of BAG3 is associated with the proteasome. Functional studies demonstrated that BAG3 indeed interacts with the proteasome and modulates its activity, sustaining cell survival and underlying resistance to therapy through the down-modulation of apoptosis. Taken as a whole, this study expands our knowledge of the BAG3 interactome, provides a valuable resource for understanding how BAG3 affects different cellular functions, and demonstrates that biologically relevant data can be harvested using this kind of integrated approach.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Linhagem Celular Tumoral , Humanos , Análise Serial de Proteínas , Mapeamento de Interação de Proteínas , Proteoma
20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(5): 1300-5, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26415448

RESUMO

Recently, the problem of food security is more and more serious, and people pay attention to mercury because of the toxic of it. A new approach for the determination of mercury content in foodstuff is devised. In this paper, first, we design and synthesis a new kind of fluorescent probe whose matrix based on rhodamine B, hydrazine hydrate and hydroxy benzaldehyde. Through the analysis of H-NMR spectra of the synthesized product L1, we confirm that the synthetic substance is the adjacent carboxyl benzaldehyde hydrazone structure generation of rhodamine B. Then, we measure the fluorescence signal intensity of the probe with different concentrations of mercury ions fully upon complexation by fluorescence spectrometer and we can study the relationship between the mercury ion concentration and the fluorescence intensity and draw the standard working curve. Following, It's time to discuss the microwave digestion processing of tea, after digestion we use the synthetic probe Li for determination of mercury content in tea. The experimental results show that the maximum excitation wavelength of the probe and coordination compound are 568. 05 and 560. 00 nm, the maximum emission wavelength are 587. 94 and 580. 00 nm. Then we can find the best testing conditions to improve the degree of accuracy, that is: room temperature, 50% the methanol solution, 3. 0 mL pH 4. 0 buffer solution, in the extent of 30 min. The experimental results show that Na+, K+, Ca2+, Cu2+, Zn2+, Al3+ have little impact on the fluorescence intensity of the:probe. Fe3+, Mg2+, Ba2+ has a weak enhancement to the fluorescence intensity of the probe. While a low concentrations of Hg2+ have an obviously enhanced effect on the fluorescence intensity of the probe. In contrast to other metal ions, the probe for Hg2+ has a good selectivity. Linear relationship between the magnitude of increase in fluorescence intensity and concentration of mercury ion was in the range of 5~20 ng . L-1 with detection limit (3S/N) of 1. 9 ng . L-1. The proposed method was applied to determination of mercury ion in samples of tea and sausage and the obtained result and sample recovery were all satisfactory. The methods of analysis instrument has the advantages of simple structure, sensitivity, high accuracy, good selectivity and less volume of simple, without the need for enrichment, being very practical.


Assuntos
Corantes Fluorescentes/química , Análise de Alimentos/métodos , Mercúrio/análise , Rodaminas/química , Espectrometria de Fluorescência , Soluções Tampão , Concentração de Íons de Hidrogênio , Íons , Limite de Detecção
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