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1.
Plant Cell ; 34(5): 1890-1911, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35166333

RESUMO

The unique morphology of grass stomata enables rapid responses to environmental changes. Deciphering the basis for these responses is critical for improving food security. We have developed a planta platform of single-nucleus RNA-sequencing by combined fluorescence-activated nuclei flow sorting, and used it to identify cell types in mature and developing stomata from 33,098 nuclei of the maize epidermis-enriched tissues. Guard cells (GCs) and subsidiary cells (SCs) displayed differential expression of genes, besides those encoding transporters, involved in the abscisic acid, CO2, Ca2+, starch metabolism, and blue light signaling pathways, implicating coordinated signal integration in speedy stomatal responses, and of genes affecting cell wall plasticity, implying a more sophisticated relationship between GCs and SCs in stomatal development and dumbbell-shaped guard cell formation. The trajectory of stomatal development identified in young tissues, and by comparison to the bulk RNA-seq data of the MUTE defective mutant in stomatal development, confirmed known features, and shed light on key participants in stomatal development. Our study provides a valuable, comprehensive, and fundamental foundation for further insights into grass stomatal function.


Assuntos
Estômatos de Plantas , Zea mays , Humanos , Folhas de Planta/metabolismo , Estômatos de Plantas/metabolismo , Poaceae/genética , Transcriptoma/genética , Zea mays/genética
2.
Plant Biotechnol J ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38761386

RESUMO

Seed vigour, including rapid, uniform germination and robust seedling establishment under various field conditions, is becoming an increasingly essential agronomic trait for achieving high yield in crops. However, little is known about this important seed quality trait. In this study, we performed a genome-wide association study to identify a key transcription factor ZmRap2.7, which regulates seed vigour through transcriptionally repressing expressions of three ABA signalling genes ZmPYL3, ZmPP2C and ZmABI5 and two phosphatidylethanolamine-binding genes ZCN9 and ZCN10. In addition, ZCN9 and ZCN10 proteins could interact with ZmPYL3, ZmPP2C and ZmABI5 proteins, and loss-of-function of ZmRap2.7 and overexpression of ZCN9 and ZCN10 reduced ABA sensitivity and seed vigour, suggesting a complex regulatory network for regulation of ABA signalling mediated seed vigour. Finally, we showed that four SNPs in ZmRap2.7 coding region influenced its transcriptionally binding activity to the downstream gene promoters. Together with previously identified functional variants within and surrounding ZmRap2.7, we concluded that the distinct allelic variations of ZmRap2.7 were obtained independently during maize domestication and improvement, and responded separately for the diversities of seed vigour, flowering time and brace root development. These results provide novel genes, a new regulatory network and an evolutional mechanism for understanding the molecular mechanism of seed vigour.

3.
BMC Pulm Med ; 24(1): 280, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877486

RESUMO

BACKGROUND: The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of co-occurring T-cell lymphocytosis and osseous metastasis being exceedingly rare. CASE PRESENTATION: A 51-year-old woman was admitted to our hospital with dyspnea and chest pain. Upon imaging examination, she was found to have diffuse and nodular pleural thickening on the left side, collapse of the left lung and a compression in the second thoracic vertebrae. All lesions showed significant 18F-FDG uptake on 18F-FDG PET/CT examination. Furthermore, she exhibited T-cell lymphocytosis in her peripheral blood, lymph nodes, and bone marrow. After ruling out malignant pleural mesothelioma (MPM), lung cancer with pleural metastasis, and T-cell lymphoma, the definitive diagnosis asserted was ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis. CONCLUSION: Physicians need to expand their knowledge of the imaging features of ectopic pleural thymoma. Cases with T-cell lymphocytosis may exhibit increased aggressiveness and prone to bone metastasis.


Assuntos
Neoplasias Ósseas , Linfocitose , Neoplasias Pleurais , Timoma , Humanos , Feminino , Pessoa de Meia-Idade , Timoma/patologia , Timoma/diagnóstico por imagem , Timoma/complicações , Timoma/diagnóstico , Linfocitose/patologia , Linfocitose/diagnóstico , Neoplasias Pleurais/secundário , Neoplasias Pleurais/patologia , Neoplasias Pleurais/complicações , Neoplasias Pleurais/diagnóstico , Neoplasias Ósseas/secundário , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias do Timo/patologia , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico , Linfócitos T/patologia , Fluordesoxiglucose F18 , Diagnóstico Diferencial , Pleura/patologia , Pleura/diagnóstico por imagem
4.
J Integr Plant Biol ; 66(1): 143-159, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37975264

RESUMO

Plants have evolved complex physical and chemical defense systems that allow them to withstand herbivory infestation. Composed of a complex mixture of very-long-chain fatty acids (VLCFAs) and their derivatives, cuticular wax constitutes the first physical line of defense against herbivores. Here, we report the function of Glossy 8 (ZmGL8), which encodes a 3-ketoacyl reductase belonging to the fatty acid elongase complex, in orchestrating wax production and jasmonic acid (JA)-mediated defenses against herbivores in maize (Zea mays). The mutation of GL8 enhanced chemical defenses by activating the JA-dependent pathway. We observed a trade-off between wax accumulation and JA levels across maize glossy mutants and 24 globally collected maize inbred lines. In addition, we demonstrated that mutants defective in cuticular wax biosynthesis in Arabidopsis thaliana and maize exhibit enhanced chemical defenses. Comprehensive transcriptomic and lipidomic analyses indicated that the gl8 mutant confers chemical resistance to herbivores by remodeling VLCFA-related lipid metabolism and subsequent JA biosynthesis and signaling. These results suggest that VLCFA-related lipid metabolism has a critical role in regulating the trade-offs between cuticular wax and JA-mediated chemical defenses.


Assuntos
Arabidopsis , Herbivoria , Zea mays/metabolismo , Proteínas de Plantas/metabolismo , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo
5.
J Med Virol ; 95(12): e29300, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38063070

RESUMO

Little is known about antibody responses to natural Omicron infection and the risk factors for poor responders in patients with hematological malignancies (HM). We conducted a multicenter, prospective cohort study during the latest Omicron wave in Chongqing, China, aiming to compare the antibody responses, as assessed by IgG levels of anti-receptor binding domain of spike protein (anti-S-RBD), to Omicron infection in the HM cohort (HMC) with healthy control cohort (HCC), and solid cancer cohort (SCC). In addition, we intend to explore the risk factors for poor responders in the HMC. Among the 466 HM patients in this cohort, the seroconversion rate was 92.7%, no statistically difference compared with HCC (98.2%, p = 0.0513) or SCC (100%, p = 0.1363). The median anti-S-RBD IgG titer was 29.9 ng/mL, significantly lower than that of HCC (46.9 ng/mL, p < 0.0001) or SCC (46.2 ng/mL, p < 0.0001). Risk factors associated with nonseroconversion included no COVID-19 vaccination history (odds ratio [OR] = 4.58, 95% confidence interval [CI]: 1.75-12.00, p = 0.002), clinical course of COVID-19 ≤ 7 days (OR = 2.86, 95% CI: 1.31-6.25, p = 0.008) and severe B-cell reduction (0-10/µL) (OR = 3.22, 95% CI: 1.32-7.88, p = 0.010). Risk factors associated with low anti-S-RBD IgG titer were clinical course of COVID-19 ≤ 7 days (OR = 2.58, 95% CI: 1.59-4.18, p < 0.001) and severe B-cell reduction (0-10/µL) (OR = 2.87, 95% CI: 1.57-5.24, p < 0.001). This study reveals a poor antibody responses to Omicron (BA.5.2.48) infection in HM patients and identified risk factors for poor responders. Highlights that HM patients, especially those with these risk factors, may be susceptible to SARS-CoV-2 reinfection, and the postinfection vaccination strategies for these patients should be tailored. Clinical trial: ChiCTR2300071830.


Assuntos
COVID-19 , Neoplasias Hematológicas , Humanos , Formação de Anticorpos , SARS-CoV-2 , Estudos Prospectivos , Neoplasias Hematológicas/complicações , Progressão da Doença , Imunoglobulina G , Anticorpos Antivirais
6.
Ann Hematol ; 102(12): 3465-3475, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37615680

RESUMO

This study comprehensively incorporates pathological parameters and novel clinical prognostic factors from the international prognostic index (IPI) to develop a nomogram prognostic model for overall survival in patients with diffuse large B-cell lymphoma (DLBCL). The aim is to facilitate personalized treatment and management strategies. This study enrolled a total of 783 cases for analysis. LASSO regression and stepwise multivariate COX regression were employed to identify significant variables and build a nomogram model. The calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) curve were utilized to assess the model's performance and effectiveness. Additionally, the time-dependent concordance index (C-index) and time-dependent area under the ROC curve (AUC) were computed to validate the model's stability across different time points. The study utilized 8 selected clinical features as predictors to develop a nomogram model for predicting the overall survival of DLBCL patients. The model exhibited robust generalization ability with an AUC exceeding 0.7 at 1, 3, and 5 years. The calibration curve displayed evenly distributed points on both sides of the diagonal, and the slopes of the three calibration curves were close to 1 and statistically significant, indicating high prediction accuracy of the model. Furthermore, the model demonstrated valuable clinical significance and holds the potential for widespread adoption in clinical practice. The novel prognostic model developed for DLBCL patients incorporates readily accessible clinical parameters, resulting in significantly enhanced prediction accuracy and performance. Moreover, the study's use of a continuous general cohort, as opposed to clinical trials, makes it more representative of the broader lymphoma patient population, thus increasing its applicability in routine clinical care.


Assuntos
Linfoma Difuso de Grandes Células B , Nomogramas , Humanos , Prognóstico , Estudos de Coortes , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , China/epidemiologia
7.
J Nanobiotechnology ; 21(1): 240, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37491290

RESUMO

Acute myeloid leukemia (AML) is an invasive hematopoietic malignancy caused by excessive proliferation of myeloblasts. Classical chemotherapies and cell transplantation therapies have remarkable efficacy in AML treatment; however, 30-40% of patients relapsed or had refractory disease. The resistance of AML is closely related to its inherent cytogenetics or various gene mutations. Recently, phytonanomedicine are found to be effective against resistant AML cells and have become a research focus for nanotechnology development to improve their properties, such as increasing solubility, improving absorption, enhancing bioavailability, and maintaining sustained release and targeting. These novel phytonanomedicine and mineral nanomedicine, including nanocrystals, nanoemulsion, nanoparticles, nanoliposome, and nanomicelles, offer many advantages, such as flexible dosages or forms, multiple routes of administration, and curative effects. Therefore, we reviewed the application and progress of phytomedicine in AML treatment and discussed the limitations and future prospects. This review may provide a solid reference to guide future research on AML treatment.


Assuntos
Leucemia Mieloide Aguda , Nanomedicina , Humanos , Leucemia Mieloide Aguda/patologia , Protocolos de Quimioterapia Combinada Antineoplásica
8.
J Cell Mol Med ; 26(19): 5067-5077, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36056692

RESUMO

Little is known about the incidence, clinical characteristics and prognostic factors in HIV associated lymphoma as these are less common than HIV-negative lymphoma in China. Currently, there are no standard guidelines for treatment of these patients. Therefore, we performed a study to analyse the clinical characteristics and outcomes of newly diagnosed HIV-associated aggressive B-cell non-Hodgkin's lymphoma (NHL) patients in Chongqing University Cancer Hospital (CUCH). Totally 86 newly diagnosed HIV-associated aggressive B-cell NHL patients in CUCH, southwest China, from July 2008 to August 2021, were analysed. In the entire cohort, median age was 48 years (range, 23-87 years), and more patients were male (87.2%). Most patients had elevated lactate dehydrogenase (LDH) (82.6%), advanced ann arbor stage (80.2%) and high IPI score (IPI score, 3-5) (62.7%) at diagnosis. Median CD4+ T-cell count at diagnosis was 191/µl (range, 4-1022), 84 patients (97.7%) were on combination antiretroviral therapy (cART) at lymphoma diagnosis. In DLBCL patients, cox multivariate analysis showed that age ≥ 60 (HR = 2.251, 95%CI 1.122-4.516; p = 0.012), elevated LDH (HR = 4.452, 95%CI 1.027-19.297; p = 0.041) and received less than two cycles of chemotherapy (HR = 0.629, 95%CI 0.589-1.071; p = 0.012) were independent risk factors for adverse prognosis based on PFS. Age ≥ 60 (HR = 3.162, 95%CI 1.500-6.665; p = 0.002) and received less than two cycles of chemotherapy (HR = 0.524, 95%CI 0.347-0.791; p = 0.002) were also independent risk factor for adverse prognosis based on OS. In BL patients, cox multivariate analysis showed that elevated LDH and received less than two cycles of chemotherapy were independent risk factors for adverse prognosis. In the DLBCL group, median PFS times in the received rituximab and no received rituximab groups were not reached and 12 months, respectively (p = 0.006). Median OS times were not reached and 36 months, respectively (p = 0.021). In the BL group, median PFS times in the received rituximab and no received rituximab groups were not reached and 4.8 months, respectively (p = 0.046). Median OS times were not reached and 10.1 months, respectively (p = 0.035). Overall, these data indicated that standardized anti-lymphoma therapy and rituximab administration were significantly associated with improved outcomes in patients with HIV-associated DLBCL and BL.


Assuntos
Infecções por HIV , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida , Doxorrubicina , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Lactato Desidrogenases , Linfoma de Células B/diagnóstico , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab/uso terapêutico , Adulto Jovem
9.
Anticancer Drugs ; 33(2): 117-123, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34561996

RESUMO

Platinum is reported to have adjuvant immune properties, whether oxaliplatin (OXA) could be utilized to synergize with anti-programmed cell death-1 (PD-1) antibody or anti-NKG2D (natural-killer group 2, member D) antibody is investigated. Subcutaneous A549 lung cancer and murine Lewis lung carcinoma (LLC) models were constructed, which were further intravenously injected with platinum-based drugs or concomitant administrated with anti-PD-1 antibody and or anti-NKG2D antibody. The tumor volume and the proportion of myeloid cells (CD45+CD11b+), CD3+T cells and NK (NK1.1+) cells were detected. The relative expression of chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10 and CXCL11 and C-X-C motif chemokine receptor 3 (CXCR3) was detected with the ELISA, western blot and flow cytometry. The three platinum drugs (cisplatin, DDP; carboplatin, CBP; OXA) showed similar effects to inhibit A549 tumor growth in immune-deficient mice. While OXA exhibited better antitumor efficacy in wild-type mice bearing LLC with downregulated myeloid cells proportion, upregulated concentration of CXCL9, CXCL10 and CXCL11, and upregulated proportion and CXCR3 expression on T cells and NK cells. OXA combined with anti-PD1 or anti-NKG2D synergistically improved tumor growth inhibition and survival. The combination of OXA to anti-PD1 and anti-NKG2D antibodies will provide the most appropriate treatment benefit. Oxaliplatin promotes T cells and NK cells infiltration through the CXCL9/10/11-CXCR3 axis to enhance anti-PD1 or anti-NKG2D immunotherapy in lung cancer.


Assuntos
Antineoplásicos/farmacologia , Quimiocinas CXC/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Compostos Organoplatínicos/farmacologia , Células A549 , Animais , Antígenos de Superfície , Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Carboplatina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/administração & dosagem , Cisplatino/farmacologia , Combinação de Medicamentos , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Ligantes , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides/efeitos dos fármacos , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina/farmacologia , Linfócitos T , Carga Tumoral/efeitos dos fármacos
10.
Mol Ther ; 28(3): 901-913, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-31991109

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a predominant cancer type in developing countries such as China, where ESCC accounts for approximately 90% of esophageal malignancies. Lacking effective and targeted therapy contributes to the poor 5-year survival rate. Recent studies showed that about 30% of ESCC cases have high levels of SOX2. Herein, we aim to target this transcription factor with aptamer. We established a peptide aptamer library and then performed an unbiased screening to identify several peptide aptamers including P42 that can bind and inhibit SOX2 downstream target genes. We further found that P42 overexpression or incubation with a synthetic peptide 42 inhibited the proliferation, migration, and invasion of ESCC cells. Moreover, peptide 42 treatment inhibited the growth and metastasis of ESCC xenografts in mouse and zebrafish. Further analysis revealed that P42 overexpression led to alternations in the levels of proteins that are important for the proliferation and migration of ESCC cells. Taken together, our study identified the peptide 42 as a key inhibitor of SOX2 function, reducing the proliferation and migration of ESCC cells in vitro and in vivo, and thereby offering a potential therapy against ESCC.


Assuntos
Antineoplásicos/farmacologia , Aptâmeros de Peptídeos/farmacologia , Fatores de Transcrição SOXB1/antagonistas & inibidores , Animais , Aptâmeros de Peptídeos/química , Aptâmeros de Peptídeos/metabolismo , Biomarcadores Tumorais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Ensaios de Seleção de Medicamentos Antitumorais , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/mortalidade , Humanos , Camundongos , Terapia de Alvo Molecular , Prognóstico , Ligação Proteica , Técnica de Seleção de Aptâmeros , Fatores de Transcrição SOXB1/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra
11.
Carcinogenesis ; 39(11): 1380-1388, 2018 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-30184109

RESUMO

Melanoma has a high propensity to metastasize and exhibits a poor response to classical therapies. Dysregulation of the chemokine receptor gene CXCR4 is associated with melanoma progression, and although n-3 polyunsaturated fatty acids (PUFAs) are known to be beneficial for melanoma prevention, the underlying mechanism of this effect is unclear. Here, we used the n-3 fatty acid desaturase (Fat-1) transgenic mouse model of endogenous n-3 PUFA synthesis to investigate the influence of elevated n-3 PUFA levels in a mouse model of metastatic melanoma. We found that relative to wild-type (WT) mice, Fat-1 mice exhibited fewer pulmonary metastatic colonies and improved inflammatory indices, including reduced serum tumor necrosis factor alpha (TNF-α) levels and pulmonary myeloperoxidase activity. Differential PUFA metabolites in serum were considered a key factor to alter cancer cell travelling to lung, and we found that n-6 PUFAs such as arachidonic acid induced CXCR4 protein expression although n-3 PUFAs such as eicosapentaenoic acid (EPA) decreased CXCR4 levels. In addition, serum levels of the bioactive EPA metabolite, 18-HEPE, were elevated in Fat-1 mice relative to WT mice, and 18-HEPE suppressed CXCR4 expression in B16-F0 cells. Moreover, relative to controls, numbers of pulmonary metastatic colonies were reduced in WT mice receiving intravenous injections either of 18-HEPE or 18-HEPE-pretreated melanoma cells. Our results indicate that 18-HEPE is a potential anticancer metabolite that mediates, at least in part, the preventive effect of n-3 PUFA on melanoma metastasis.


Assuntos
Caderinas/genética , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/metabolismo , Ácidos Hidroxieicosatetraenoicos/farmacologia , Melanoma Experimental/patologia , Receptores CXCR4/metabolismo , Animais , Ácido Araquidônico/metabolismo , Linhagem Celular Tumoral , Crisenos , Modelos Animais de Doenças , Ácido Eicosapentaenoico/sangue , Ácido Eicosapentaenoico/farmacologia , Ácidos Graxos Ômega-3/biossíntese , Ácidos Graxos Ômega-3/genética , Feminino , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Metástase Neoplásica/prevenção & controle , Peroxidase/metabolismo , Receptores CXCR4/genética , Fator de Necrose Tumoral alfa/sangue
12.
J Nanobiotechnology ; 16(1): 76, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30290822

RESUMO

BACKGROUND: Recently, we found that berberine (BBR) exerts anti-acute myeloid leukemia activity, particularly toward high-risk and relapsed/refractory acute myeloid leukemia MV4-11 cells in vitro. However, the poor water solubility and low bioavailability observed with oral BBR administration has limited its clinical use. Therefore, we design and develop a novel oil-in-water self-nanoemulsifying system for BBR (BBR SNE) to improve oral bioavailability and enhance BBR efficacy against acute myeloid leukemia by greatly improving its solubility. RESULTS: This system (size 23.50 ± 1.67 nm, zeta potential - 3.35 ± 0.03 mV) was prepared with RH40 (surfactant), 1,2-propanediol (co-surfactant), squalene (oil) and BBR using low-energy emulsification methods. The system loaded BBR successfully according to thermal gravimetric, differential scanning calorimetry, and Fourier transform infrared spectroscopy analyses. The release profile results showed that BBR SNE released BBR more slowly than BBR solution. The relative oral bioavailability of this novel system in rabbits was significantly enhanced by 3.41-fold over that of BBR. Furthermore, Caco-2 cell monolayer transport studies showed that this system could help enhance permeation and prevent efflux of BBR. Importantly, mice with BBR SNE treatment had significantly longer survival time than BBR-treated mice (P < 0.001) in an MV4-11 engrafted leukemia murine model. CONCLUSIONS: These studies confirmed that BBR SNE is a promising therapy for acute myeloid leukemia.


Assuntos
Absorção Fisiológica , Berberina/uso terapêutico , Emulsões/química , Leucemia Mieloide Aguda/tratamento farmacológico , Nanopartículas/química , Administração Oral , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Berberina/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citarabina/farmacologia , Citarabina/uso terapêutico , Interações Medicamentosas , Liberação Controlada de Fármacos , Leucemia Mieloide Aguda/patologia , Camundongos , Nanopartículas/ultraestrutura , Permeabilidade , Transição de Fase , Coelhos , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Med Sci Monit ; 24: 5973-5979, 2018 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-30148822

RESUMO

BACKGROUND Acute graft-versus-host disease (aGVHD) limits the wider application of hematopoietic stem cell transplantation (HSCT). We explored the relationship between the Nrf2-ARE signaling pathway and aGVHD and identified effective and efficient therapeutic targets for the prevention and management of aGVHD following HSCT. MATERIAL AND METHODS C57BL/6 and BALB/c mice were used to establish the aGVHD model. The bone marrow and spleen mononuclear cells were separated from the donor mice and injected into the caudal vein of recipient mice that had undergone total body irradiation (TBI, 8 Gy). Sulforaphane (SFN) was used to activate the Nrf2-ARE signaling pathway. RESULTS The long-term survival rate of the SFN group was higher than that of the control group (40% vs. 0%, p<0.05, n=10). There were worse pathological changes and a greater infiltration of inflammatory cells in the liver, small intestine, and lung tissues of the control group. Furthermore, the Nrf2, NQO1, and HO-1 mRNA and protein levels were higher in the small intestines of the SFN group than in the control group (p<0.05, n=4). CONCLUSIONS The Nrf2-ARE signaling pathway plays a vital role in preventing aGVHD in an HSCT mouse model by regulating the expression of the downstream antioxidant genes NQO1 and HO-1 and by inhibiting the local inflammatory reaction.


Assuntos
Elementos de Resposta Antioxidante , Doença Enxerto-Hospedeiro/metabolismo , Transplante de Células-Tronco Hematopoéticas/métodos , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Células da Medula Óssea/citologia , Modelos Animais de Doenças , Feminino , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Heme Oxigenase-1/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Leucócitos Mononucleares/citologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/genética , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Distribuição Aleatória , Transdução de Sinais , Baço/citologia , Transplante Homólogo
14.
J Nanosci Nanotechnol ; 18(8): 5155-5170, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29458567

RESUMO

Nanotechnology for early diagnosis and treatment of malignant tumor is a forefront topic in the international field of biotechnology and medicine. In order to improve the effect of cancer therapy, the timely and accurate detection of the cancer is important and necessary. Graphene and its derivatives have various excellent characteristics. For example, biological sensors based on graphene are good at amplifying detection signals, and its derivatives play an important role in the early diagnosis and cancer therapy. In view of this, we discussed the biological sensor application based on graphene and its derivatives in the detection and therapy of cancer.


Assuntos
Grafite , Nanoestruturas , Nanotecnologia , Técnicas Biossensoriais , Biotecnologia , Neoplasias/diagnóstico , Neoplasias/terapia
15.
J Nanosci Nanotechnol ; 18(8): 5192-5206, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29458569

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common cancers around the world. Multiple etiologic factors such as virus and environment can lead to HCC. It is a challenge for us to successfully detect early HCC due to the lack of effective characterized and specific biomarkers. However, if the early diagnosis is successfully realized, it provides crucial chance for HCC patients to receive effective treatment as early as possible. Dickkopf-1 (DKK-1) is a secretary glycoprotein, which negatively regulates Wnt pathway through binding to surface receptors LRP5/6 and Kremen 1/2. The expression of DKK-1 is regulated by p53, V-Myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN), ß-catenin, etc. Ectopic expression of DKK-1 can inhibit cell proliferation, or induce apoptosis with apoptosis enhancing factors. DKK-1 is low-expressed in many tumors, but overexpressed in others. Growing evidences show that DKK-1 plays complex and different roles in tumorigenesis, tumor progression and metastasis of different cancers. We herein review the recent progress in the expression and function of DKK-1 in hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Hepáticas/metabolismo , Via de Sinalização Wnt , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico
16.
Tumour Biol ; 37(3): 3043-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26423399

RESUMO

Gastric cancer is one of the leading causes of cancer death worldwide. However, precise molecular mechanisms underlining its development are far from clear. We recently reported that PES1 promoted development of breast cancer and ovarian cancer as an oncogene. In this study, we reported that ablation of endogenous PES1 resulted in significant suppression of cell proliferation and growth and led to cell cycle arrest in G2 or G1 phase, respectively, in two gastric cancer cell lines (AGS and N87) in vitro. Meanwhile, silencing of PES1 obviously decreased expressions of cyclin D1, HIF-1α, and vascular endothelial growth factor (VEGF) expressions and increased p21WAF1 expression. Re-expression of PES1 in these two kinds of PES1 knockdown cells rescued these effects. In vivo, repression of endogenous PES1 expression suppressed gastric tumor growth in nude mice. In addition, 40.7 % (24/59) of gastric cancer tissues showed PES1 expression via immunohistochemical (IHC) staining. However, there were not any positive PES1 stainings in matched adjacent tissues. Our results demonstrated that repression of PES1 changed expressions of some cell proliferation- and angiogenesis-related genes and inhibited gastric cancer growth, and PES1 expression increased in gastric cancer tissues. These results suggest that PES1 may play an important role in development of gastric cancer. PES1 may be a potential target for gastric cancer therapy.


Assuntos
Proteínas/fisiologia , Neoplasias Gástricas/patologia , Animais , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Proteínas/análise , Proteínas de Ligação a RNA , Neoplasias Gástricas/irrigação sanguínea , Neoplasias Gástricas/etiologia
17.
J Integr Plant Biol ; 58(3): 266-79, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26593310

RESUMO

Maize (Zea mays) root system architecture (RSA) mediates the key functions of plant anchorage and acquisition of nutrients and water. In this study, a set of 204 recombinant inbred lines (RILs) was derived from the widely adapted Chinese hybrid ZD958(Zheng58 × Chang7-2), genotyped by sequencing (GBS) and evaluated as seedlings for 24 RSA related traits divided into primary, seminal and total root classes. Significant differences between the means of the parental phenotypes were detected for 18 traits, and extensive transgressive segregation in the RIL population was observed for all traits. Moderate to strong relationships among the traits were discovered. A total of 62 quantitative trait loci (QTL) were identified that individually explained from 1.6% to 11.6% (total root dry weight/total seedling shoot dry weight) of the phenotypic variation. Eighteen, 24 and 20 QTL were identified for primary, seminal and total root classes of traits, respectively. We found hotspots of 5, 3, 4 and 12 QTL in maize chromosome bins 2.06, 3.02-03, 9.02-04, and 9.05-06, respectively, implicating the presence of root gene clusters or pleiotropic effects. These results characterized the phenotypic variation and genetic architecture of seedling RSA in a population derived from a successful maize hybrid.


Assuntos
Endogamia , Raízes de Plantas/anatomia & histologia , Raízes de Plantas/genética , Característica Quantitativa Herdável , Recombinação Genética/genética , Plântula/genética , Zea mays/genética , Marcadores Genéticos , Hidroponia , Fenótipo , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Plântula/crescimento & desenvolvimento
18.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(6): 654-8, 2016 Jun.
Artigo em Zh | MEDLINE | ID: mdl-27491220

RESUMO

OBJECTIVE: To explore the effect of Scalp acupuncture on serum neuron specific enolase (NSE) and S-100ß concentrations, and incidence rates of postoperative delirium (POD) and postoperative cognitive function (POCD) of elderly patients undergoing hip replacement. METHODS: Eighty-four patients undergoing scheduled hip replacement under combined spinal-epidural anesthesia (CSEA) were assigned to the control group (group C) and the scalp acupuncture group (group S) according to random digit table, 42 cases in each group. In group S, scalp acupuncture was additionally performed according to International Standardized Scheme for Scalp Acupuncture. Scalp acupuncture was performed during the operation from the MS1 middle line of forehead [1 cun before Shenting (GV24), including Shenting (GV24)] and MS5 middle line of vertex [from Baihui (DU20) to Qianding (DU21), including Baihui (DU20) and Qianding (DU21)]. The operation time and post-operative length of stay were observed. The midazolam dosage, hemorrhage amount, fluid transfusion amount, urine amount, use rates of ephedrine and atropine during the operation were also observed and compared between the two groups. The occurrence rate of POD and POCD at post-operative day 3 (T1), week 1 (T2), month 3 (T3), and month 6 (T4) were measured. Eighteen patients were randomly selected to collect blood from internal jugular vein before anesthesia t0), immediately after ending the surgery (t1), 6 h after operation (t2), 24 h after operation (t3), and 48 h after operation (t4), respectively. Serum levels of NSE and S-100ß were correspondingly measured. RESULTS: There was no statistical difference in the operation time, midazolam dosage used during the operation, hemorrhage amount, fluid transfusion amount, urine amount, use rates of ephedrine and atropine (P > 0.05). Compared with group C, the post-operative length of stay was shortened in group S (P < 0.05). The incidence rate of POD and that of POCD at each time point were lower in group S (P < 0.05). The expression level of NSE decreased at t2, t3, and t4, and the expression level of S100ß also decreased at t1, t2, t3, and t4(P < 0.05). There was no statistical difference in expression levels of NSE or S100ß between the two groups at other time points (P > 0.05). CONCLUSION: Scalp acupuncture could attenuate central nervous system lesion and improve POCD of elderly patients undergoing hip replacement.


Assuntos
Terapia por Acupuntura , Artroplastia de Quadril , Cognição , Fosfopiruvato Hidratase/sangue , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Pontos de Acupuntura , Idoso , Humanos , Tempo de Internação , Complicações Pós-Operatórias , Período Pós-Operatório , Couro Cabeludo
19.
Colloids Surf B Biointerfaces ; 236: 113825, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38422668

RESUMO

Dynamical control of macrophage polarization from M1 (pro-inflammatory) to M2 (anti-inflammatory) at implant surfaces is essential for balancing innate immunity and tissue repair. In this aspect, the design of orthopedic implant that can response to inflammation microenvironment with transformation in surface properties has shown promising in timely driving M1-to-M2 macrophage transition. Considering excessive reactive oxygen species (ROS) contribute to macrophage M1 polarization and progression of inflammation, in this study, ferrocene modified polydopamine (PDA-Fc) films were deposited on plasma sprayed Ti coatings to endow the implants with ROS-responsive and -scavenging abilities. Plasma sprayed Ti (PST) coating and PDA modified PST coating (PST/PDA) served as control. The presence of PDA endowed PST/PDA and PST/PDA-Fc with free-radical scavenging abilities. Moreover, PST/PDA-Fc showed adaptive wettability as evidenced by increased hydrophilicity under H2O2 treatment. With respect to PST/PDA, PST/PDA-Fc exerted greater effects on inducing lipopolysaccharides-induced M1 macrophages to adopt M2-type macrophage phenotype, characterized by higher percentage of CD206-positive cells, increased cell elongation rate and higher expression level of anti-inflammatory cytokine arginase type 1. The results obtained in our study may provide a prospective approach for manipulating an appropriate immune response at implant surfaces.


Assuntos
Compostos Ferrosos , Peróxido de Hidrogênio , Indóis , Macrófagos , Polímeros , Humanos , Molhabilidade , Metalocenos , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia
20.
Toxicol Res (Camb) ; 13(4): tfae102, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38993483

RESUMO

Background: Paclitaxel (PTX) is a commonly used as a chemotherapeutic drug for non-small cell lung cancer (NSCLC). Exploring the underlying mechanism of PTX resistance is of great significance for NSCLC treatment. Methods: The expression levels of RNA and protein were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The targeted relationship was confirmed by dual-luciferase reporter assay and RNA-pull down assay. The PTX resistance and cell proliferation were assessed by cell counting kit-8 (CCK-8) assay and 5-Ethynyl-2'-deoxyuridine (EDU) assay, respectively. Cell migration and invasion were analyzed by transwell assays. Cell apoptosis was analyzed by flow cytometry, and cell glycolysis was analyzed using the commercial kits. The role of circular RNA_0076305 (circ_0076305) in regulating the PTX sensitivity in vivo was explored in xenograft tumor model. Results: Circ_0076305 was up-regulated in PTX-resistant NSCLC tissues and cells. Mechanically, circ_0076305 bound to microRNA-936 (miR-936), and miR-936 targeted transmembrane serine protease 4 (TMPRSS4). Circ_0076305 could up-regulate TMPRSS4 expression by sponging miR-936 in NSCLC cells. miR-936 knockdown or TMPRSS4 overexpression reversed the anti-tumor effects of circ_0076305 knockdown in NSCLC cells with PTX treatment. Circ_0076305 silencing increased the PTX sensitivity of xenograft tumors in vivo. Conclusion: Circ_0076305 silencing promoted PTX sensitivity by targeting miR-936/TMPRSS4 axis in NSCLC cells.

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