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1.
Cell Mol Life Sci ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515577

RESUMO

Epigenetic modifications play a central role in cell differentiation and development. In the current study, we have recognized lysine demethylase 4A (KDM4A) as a novel epigenetic regulator of osteoblast and adipocyte differentiation. Kdm4a expression was upregulated during osteogenesis and adipogenesis of primary marrow stromal cells and established stromal ST2 line. Overexpression of wild-type Kdm4a promoted adipogenic differentiation and blocked osteogenic differentiation of the progenitor cells. This effect was largely alleviated when the catalytically dead mutation was made. Conversely, depletion or inactivation of Kdm4a in undifferentiated progenitor cells inhibited the formation of adipocytes and promoted the differentiation of osteoblasts. Mechanism explorations showed that overexpression of Kdm4a upregulated the expression of secreted frizzled-related protein 4 (Sfrp4) and CCAAT/enhancer-binding protein α (C/ebpα). Chromatin immunoprecipitation assay demonstrated that KDM4A directly bound the promoters of Sfrp4 and C/ebpα, removed the histone methylation mark H3K9me3, and reduced DNA methylation levels of CpG in promoter regions of C/ebpα and Sfrp4. Furthermore, overexpression of Kdm4a inactivated canonical Wnt signaling. Moreover, activation of canonical Wnt signaling through silencing of Sfrp4 in ST2 attenuated the inhibition of osteogenic differentiation and the enhancement of adipogenic differentiation by KDM4A. These data have identified KDM4A as a novel regulator of osteoblast and adipocyte differentiation and suggest KDM4A inhibition as a potential therapeutic target for treating metabolic disorders such as osteoporosis.

2.
J Mater Chem B ; 7(32): 4953-4962, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31411627

RESUMO

Malignant solid tumors are composed of tumor cells, stromal cells and the complex networks of the tumor microenvironment (TME), which is the underlying cause of the unsatisfactory outcome of conventional chemotherapy approaches only aimed at cancer cell killing. In this study, a novel TME-responsive polymeric micelle has been developed for the programmed site-specific delivery of the angiostatin sunitinib and chemotherapeutic paclitaxel (PTX). The pH-sensitive micelle core encapsulates PTX, while ß-cyclodextrin molecules being conjugated to the micelle shell via matrix metalloproteinase 2 (MMP-2) sensitive peptides include sunitinib. Following the pH and MMP-2 dual sensitive structure design, the micelle may sequentially release sunitinib inside the tumor extracellular matrix and PTX into cancer cells through responding to enriched MMP-2 levels and decreased pH, respectively. Consequently, the anti-angiogenesis effect of sunitinib and tumor cell-killing effect of PTX synergize, resulting in highly efficient tumor treatment.

4.
Int J Mol Med ; 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31364739

RESUMO

L­carnitine (LC) is well known for its antioxidative properties. The present study aimed to evaluate the effects of LC on human lens epithelial cells (HLECs) and to analyze its regulatory mechanism in cataractogenesis. HLE B­3 cells were cultured with hydrogen peroxide (H2O2) and were pretreated with or without LC. The Cell Counting kit­8 assay was used to determine cell viability. Reactive oxygen species (ROS) assay kit was used to measure the cellular ROS production induced by H2O2 and LC. In addition, reverse transcription­quantitative PCR and western blot analysis were performed to detect the expression levels of oxidative damage markers and antioxidant enzymes. Notably, ROS overproduction was observed upon exposure to H2O2, whereas LC supplementation markedly decreased ROS levels through activation of the antioxidant enzymes forkhead box O1, peroxiredoxin 4 and catalase. Furthermore, LC suppressed the expression of apoptosis­associated genes (caspase-3) and inflammation­associated genes [interleukin (IL)1, IL6, IL8 and cyclooxygenase­2]. Conversely, LC promoted proliferating cell nuclear antigen, cyclin­dependent kinase (CDK)2 and CDK4 expression, which may increase proliferation of HLECs that were incubated with H2O2. In addition, epithelial­mesenchymal transition occurred upon ROS accumulation, whereas the effects of H2O2 on AQP1 and vimentin expression were reversed upon LC supplementation. Notably, this study revealed that LC restored the oxidant/antioxidant balance and protected against cell damage through the mitogen­activated protein kinase signaling pathway. In conclusion, LC may serve a protective role in curbing oxidative damage and therefore may be considered a potential therapeutic agent for the treatment of cataracts.

5.
Mol Med Rep ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31432138

RESUMO

The present study aimed to explore the effect of the long non­coding RNA TP73 antisense RNA 1 (TP73­AS1) on cervical cancer progression. Cervical cancer and adjacent tissues were collected from 56 patients and assessed. In addition, HeLa and CaSki cells were transfected with various plasmids, inhibitors and corresponding controls, and then Cell Counting Kit­8 and Transwell assays were used to detect the cell proliferation, migration and invasion abilities. Luciferase reporter gene assay was also performed in HeLa cells. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was used to investigate TP73­AS1, microRNA­607 (miR­607) and cyclin D2 (CCND2) gene expression, while CCND2 protein expression was determined by western blot analysis. The results revealed that the TP73­AS1 level was upregulated in cervical cancer tissues (P<0.05) and predicted a poor 5­year overall survival (P<0.05). HeLa and CaSki cells transfected with siTP73­AS1 exhibited reduced proliferation, migration and invasion abilities when compared with those in the siNC group (P<0.05). Furthermore, miR­607 was found to be negatively regulated by TP73­AS1, while CCND2 was negatively regulated by miR­607. HeLa and CaSki cells transfected with siTP73­AS1 exhibited lower CCND2 mRNA and protein expression levels compared with the siNC and siTP73­AS1 + miR­inhibitor groups (P<0.05). Compared with the siNC and siTP73­AS1 + CCND2 overexpression groups, siTP73­AS1­transfected HeLa and CaSki cells had decreased proliferation, migration and invasion abilities (P<0.05). In conclusion, the findings suggested that upregulation of TP73­AS1 promoted cervical cancer progression by promoting CCND2 via the suppression of miR­607 expression.

6.
J Hazard Mater ; 382: 121081, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31470296

RESUMO

Herein, a new peroxymonosulfate (PMS) activation system was proposed employing nonredox metal ions as Lewis acids (LA), which have been widely recognized to play important roles in many biological and chemical oxidations. With Co2+ ions as model catalysts, it was found that oxidizing power of PMS was enhanced after binding weak LA such as Ca2+ ions, leading to its easier reduction to active radicals and substantial enhancement of dye degradation. The promoting effect of Ca2+ was also observed with other cobalt catalysts including CoFe2O4 and Co3O4. The rate of PMS decomposition in Co2++LA/PMS system was correlated with Lewis acidity; while in the presence of strong LA including La3+ and Y3+, the dye degradation rate declined. The interactions of LA with PMS were characterized and the detailed mechanism was proposed. The present study provides the first example of the promoting effect of weak LA on PMS activation with cobalt based catalysts.

7.
Clin Cancer Res ; 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350313

RESUMO

PURPOSE: Early detection and intervention can decrease the mortality of breast cancer significantly. Assessments of genetic/genomic variants in circulating tumor DNA (ctDNA) have generated great enthusiasm for their potential application as clinically actionable biomarkers in the management of early-stage breast cancer. EXPERIMENTAL DESIGN: In current study, 861 serial plasma and matched tissue specimens from 102 patients with early-stage breast cancer who need chemotherapy and 50 individuals with benign breast tumors were deeply sequenced via next-generation sequencing (NGS) techniques using large gene panels. RESULTS: Cancer tissues in this cohort of patients showed profound intratumor heterogeneities (ITHGs) that were properly reflected by ctDNA testing. Integrating the ctDNA detection rate of 74.2% in this cohort with the corresponding predictive results based on Breast Imaging Reporting and Data System classification (BI-RADS) could increase the positive predictive value up to 92% and potentially dramatically reduce surgical overtreatment. Patients with positive ctDNA after surgery showed a higher percentage of lymph node metastasis, indicating potential recurrence and remote metastasis. The ctDNA-positive rates were significantly decreased after chemotherapy in basal-like and Her2+ tumor subtypes but were persistent despite chemotherapy in luminal type. The tumor mutation burden in blood (bTMB) assessed based on ctDNA testing was positively correlated with the TMB in tumor tissues (tTMB), providing a candidate biomarker warranting further study of its potentials used for precise immunotherapy in cancer. CONCLUSION: These data showed that ctDNA evaluation is a feasible, sensitive and specific biomarker for diagnosis and differential diagnosis of early-stage breast cancer who need chemotherapy.

8.
Nat Commun ; 10(1): 3353, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350389

RESUMO

The diverse repertoire of T cell receptors (TCR) and immunoglobulins is generated through the somatic rearrangement of respective V, D and J gene segments, termed V(D)J recombination, during early T or B cell development. However, epigenetic regulation of V(D)J recombination is still not fully understood. Here we show that the deficiency of Setd2, a histone methyltransferase that catalyzes lysine 36 trimethylation on histone 3 (H3K36me3) in mice, causes a severe developmental block of thymocytes at the CD4-CD8- DN3 stage. While H3K36me3 is normally enriched at the TCRß locus, Setd2 deficiency reduces TCRß H3K36me3 and suppresses TCRß V(D)J rearrangement by impairing RAG1 binding to TCRß loci and the DNA double-strand break repair. Similarly, Setd2 ablation also impairs immunoglobulin V(D)J rearrangement to induce B cell development block at the pro-B stage. Lastly, SETD2 is frequently mutated in patients with primary immunodeficiency. Our study thus demonstrates that Setd2 is required for optimal V(D)J recombination and normal lymphocyte development.

9.
PLoS One ; 14(7): e0215585, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31306422

RESUMO

Tick-borne pathogens (TBPs) seriously affect cattle production and can be economically damaging. The epidemiology of these organisms in the Chongqing municipality of China is not well described. This study aimed to investigate the prevalence and risk factors of TBPs including Anaplasma spp., Babesia spp. and Theileria spp. in cattle in Chongqing municipality. The results showed that 43.48% (150/345) of cattle were infected with at least one TBP, of which single infections were detected in 104 (30.14%), double infections in 34 cattle (9.86%) and triple infections in 12 (3.48%) of the cattle. The overall prevalence of Anaplasma spp., Theileria spp. and B. bigemina were 22.32%, 23.19% and 7.24%, respectively. Among these, the prevalence of A. bovis, A. central, A. phagocytophilum, A. platys, A. marginale, T. sinensisi and T. orientalis were 8.41%, 7.83%, 4.93%, 4.35%, 2.61%, 22.32% and 2.60%, respectively. We could not detect B. bovis, T. annulata, T. luwenshuni or T. uilenbergi in cattle. Cattle ≥1-year-old were more likely to be infected with Theileria spp. [adjusted odd ratio (AOR) = 2.70, 95% CI = 1.12-6.56)] compared with younger cattle, while cattle ≥1-year-old had reduced susceptibility to B. bigemina (AOR = 0.14, 95% CI = 0.03-0.60). Cattle living at higher altitude (≥500 m) were more susceptible to B. bigemina (AOR = 6.97, 95% CI = 2.08-23.35) and Theileria spp. infection (AOR = 1.87, 95% CI = 1.06-3.32). The prevalence of Theileria spp. on farms with cats was significantly higher than that without cats (AOR = 2.56, 95% CI = 1.12-5.88). Infection with A. bovis and A. central were significantly associated with A. phagocytophilum infection. Furthermore, there were significant associations between A. bovis and A. central infection, T. sinensisi and A. marginale infection, and B. bigemina and T. orientalis infection. This study provides new data on the prevalence of Anaplasma spp., Babesia spp. and Theileria spp. in cattle in Chongqing, and for the first time we reveal a possible relationship between the afore-mentioned pathogens, which will help in formulating appropriate control strategies for these pathogens in this area.

10.
Taiwan J Obstet Gynecol ; 58(4): 501-504, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31307741

RESUMO

OBJECTIVE: This study aims to evaluate the value of the ultrasound-related scoring system on pregnant patients receiving assisted reproductive technology (IVF/ICSI) and early pregnancy outcome. MATERIALS AND METHODS: This prospective study included 208 pregnant women receiving assisted reproductive technology (IVF/ICSI). The following ultrasound parameters were measured: gestational sac size, the proportion of the embryo and gestational sac (embryo/gestational sac), yolk sac size, and fetal cardiac activity. The above data were assigned according to the ongoing pregnancy rate (up to 14 weeks), and the score increased parallel to the pregnancy rate. All patients were grouped according to their scores. RESULTS: Patients with a score of 4-5 had a low ongoing pregnancy rate of 14.29%, while patients with a score of 6-7 had an ongoing pregnancy rate of 55.56%. Surprisingly, patients with a score of 8-9 had an ongoing pregnancy rate of 97.22%. In addition, it was found that the ongoing pregnancy rate was 100% (36/36) in patients with a score of 9. Conversely, there was no ongoing pregnancy in patients with a score of 4. CONCLUSION: First, this scoring system is strongly associated with an ongoing pregnancy of over 14 weeks. Second, some reassurance can be given to patients with favorable ultrasound parameters, regardless of maternal age or previous pregnancy loss. Third, it would be meaningless to continue the pregnancy in patients with a score of 4, according to the scoring system. Fourth, patients without cardiac activity and embryos at days 33-35 after embryo transfer should discontinue the pregnancy, while patients with embryos should proceed with the pregnancy.

11.
Methods Mol Biol ; 2011: 331-344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31273708

RESUMO

Post-traumatic stress disorder (PTSD) is a chronic, debilitating mental disorder afflicting more than 7% of the US population and 12% of military service members. Since the Afghanistan and Iraq wars, thousands of US service members have returned home with PTSD. Despite recent progress, the molecular mechanisms underlying the pathology of PTSD are poorly understood. To promote research on PTSD (especially its molecular mechanisms) and to set a molecular basis for discovering novel medications for this disorder, well-validated animal models are needed. However, to develop PTSD animal models is a challenging process, due to predisposing factors such as physiological, behavioral, emotional, and cognitive changes that emerge after trauma. Currently, there is no well-validated animal model of PTSD, although several stress paradigms mimic the behavioral symptoms and neurological alterations seen in PTSD. In this chapter, we will provide an overview of animal models of PTSD including learned helplessness, footshock, restraint stress, inescapable tail shock, single-prolonged stress, underwater trauma, social isolation, social defeat, early-life stress, and predator-based stress. We emphasize rodent models because they reproduce some of the behavioral and biotical phenotypes seen in PTSD. We will also present data showing that homologous biological measures are increasingly incorporated in studies to assess markers of risk and therapeutic response in these models. Therefore, PTSD animal models may be refined in hopes of capitalizing on the understanding of the molecular mechanisms and delivering tools in order to develop new and more efficacious treatments for PTSD.

12.
Front Immunol ; 10: 1293, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31316496

RESUMO

Tumor necrosis factor receptor (TNFR)-associated factors or (TRAFs) are important mediators of Interleukin-17 (IL-17) cytokine signaling and contribute to driving tissue responses that are crucial for protective immunity but are often implicated in immunopathology. By amplifying tissue immune activity, IL-17 cytokine pathways contribute to maintaining barrier function as well as activation of innate and adaptive immunity necessary for host defense. IL-17 receptors signaling is orchestrated in part, by the engagement of TRAFs and the subsequent unlocking of downstream cellular machinery that can promote pathogen clearance or contribute to immune dysregulation, chronic inflammation, and disease. Originally identified as signaling adaptors for TNFR superfamily, TRAF proteins can mediate the signaling of a variety of intercellular and extracellular stimuli and have been shown to regulate the downstream activity of many cytokine receptors including receptors for IL-1ß, IL-2, IL-6, IL-17, IL-18, IL-33, type I IFNs, type III IFNs, GM-CSF, M-CSF, and TGF-ß Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I- like receptors, and C-type lectin receptors. This review will focus on discussing studies that reveal our current understanding of how TRAFs mediate and regulate biochemical activities downstream of the IL-17 cytokines signaling.

13.
Int J Radiat Oncol Biol Phys ; 105(2): 319-328, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31228553

RESUMO

PURPOSE: Clinical tools are unavailable for accurate prediction of pathologic responses to chemoradiation therapy (CRT) among patients with esophageal squamous cell carcinoma (ESCC) before surgery. We evaluated tumor remission and tumor-infiltrating lymphocytes (TILs) during CRT as predictors of pathologic response and prognostic markers for patients with locally advanced ESCC treated with neoadjuvant CRT (neo-CRT) or definitive CRT. METHODS AND MATERIALS: We analyzed patients with locally advanced ESCC (N = 164) who underwent neo-CRT (N = 48) or definitive CRT (N = 116). Patients underwent endoscopic ultrasonography and biopsies when induction CRT finished. Tumor remission characteristics were designated minor (-/+) to excellent remission (ER) (+++). TILs were determined in 10% increments. Tumor remission, TILs, or both were associated with pathologic complete response (pCR) and survival in the neo-CRT group and then analyzed in the definitive CRT group. RESULTS: ER and lymphocyte-predominant ESCC (LPE; ≥60% TILs) were identified according to the pCR rate and disease-free survival. We built a prediction model for pCR incorporating ER and LPE. The area under the receiver operating characteristic curve was 0.877, and sensitivity and specificity were 86.7% and 90.9%, respectively. Furthermore, this model identified pathologic response with an excellent calibration. Disease-free survival of patients with ER and LPE tumors was significantly longer than that of other patients. CONCLUSIONS: When we included tumor remission and TILs during CRT, our model predicted pCR with high probability and helped stratify prognostic subgroups, thereby guiding future therapy decisions for patients with locally advanced ESCC. Validation of this model in larger, prospective, multicenter studies is essential.

14.
BMC Ophthalmol ; 19(1): 130, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208396

RESUMO

BACKGROUND: Nerve growth factor (NGF), produced by Müller cells, and internal limiting membrane (ILM) have fundamental roles in the development of full-thickness macular hole (FTMH). However, the potential crosstalk between NGF and ILM in FTMH is unclear. This study aimed to explore the mechanism and effects of NGF on the proliferation of Müller cells co-cultured with ILM. METHODS: Primary Müller cells and ILM from New Zealand rabbits were extracted and authenticated with specific staining. Müller cells co-cultured with or without ILM were exposed to NGF and then analysed. Müller cell viability was estimated using cell counting kit-8. Cell cycle analysis was performed by flow cytometry. The levels of cell cycle-related gene were detected using qRT-PCR. The TrK-A/Akt signal axis and downstream signaling cascades such as p21, CyclinE, CDK2, CyclinD1, and CDK4 were investigated by western blotting. RESULTS: ILM treatment alone induced the proliferation of Müller cells following the promotion of phosphorylated Akt, while growth of Müller cells was enhanced by activation of the Trk-A/Akt pathway under the stimulation of NGF or NGF + ILM. Additionally, the ratio of S-phase cells was increased, while G2-phase cells decreased upon the treatment with either ILM or NGF alone, or with NGF + ILM co-treatment. Cell cycle-related genes such as CyclinD1, CyclinE, CDK2, and CDK4 were all upregulated, but p21 expression was downregulated in the presence of NGF, ILM, or NGF + ILM. There was an additive effect on cell proliferation and cell cycle in the group of Müller cells exposed to NGF co-cultured with ILM compared with either NGF or ILM treatment alone. However, both K252ɑ (inhibitors of Trk-A) and LY294002 (inhibitor for Akt) counteracted the effect of NGF or NGF + ILM on the protein levels of Trk-A, Akt, CyclinD1, CyclinE, CDK2, and p21. CONCLUSIONS: Müller cells co-cultured with ILM or NGF promoted cell proliferation by regulating cell cycle-correlated proteins via the PI3K/Akt pathway. ILM + NGF further amplified the PI3K/Akt signaling pathway by binding to Trk-A, leading to more cell growth. This study provides new insight into the potential mechanism of NGF-mediated proliferation of Müller cells co-cultured with or without ILM, which may have considerable impact on therapies for FTMH.


Assuntos
Membrana Basal , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Ependimogliais/efeitos dos fármacos , Fator de Crescimento Neural/farmacologia , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Animais , Membrana Basal/efeitos dos fármacos , Membrana Basal/fisiologia , Técnicas de Cocultura , Células Ependimogliais/citologia , Coelhos
15.
Stroke ; 50(7): 1825-1830, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31177978

RESUMO

Background and Purpose- Stroke disability is a major health burden in rural China where rehabilitation services are inadequate. We aimed to determine the effectiveness of a novel nurse-led, caregiver-delivered model of stroke rehabilitation in rural China. Methods- A multicenter prospective, randomized open, blinded outcome assessed, controlled trial was conducted in 3 rural county hospitals in China: Zhangwu, Liaoning Province (Northeast); Qingtongxia, Ningxia Hui Autonomous Region (Northwest); and Dianjiang, Chongqing Municipality (Southwest). Adult patients (age 18-79 years) with residual disability (Barthel Index score ≤80/100) after a recent acute stroke were randomized to a new service model or usual care. The new intervention was multifaceted and was based on a task-shifting / training-the-trainers model, supported by a custom-designed smartphone application, where patients and caregivers received evidence-based in-hospital education and stroke rehabilitation training (focus on mobility, self-care, and toileting), delivered by trained nurses before hospital discharge, and 3 postdischarge support telephone calls. Outcome assessments were undertaken before hospital discharge and at 3 and 6 months. Primary outcome was physical functioning (Barthel Index scores) at 6 months, assessed by research staff blind to treatment allocation, adjusted for baseline covariates in an intention-to-treat analysis. Secondary outcomes included measures of mobility, health-related quality of life, mood, and caregiver burden. The study included a process evaluation that assessed intervention fidelity. Results- From November 2014 to December 2016, 246 stroke patients were randomized to intervention (n=118) or control (n=128) groups. There was no statistically significant difference in adjusted 6-month Barthel Index scores between groups (70.1 versus 74.1, mean difference, -4.0 [95% CI, -10.0 to 2.9]), nor any differences across the other outcome measures. Process evaluation interviews revealed that the intervention was desirable and positively accepted by nurses, caregivers, and patients but was considered too complex despite efforts to simplify materials for the rural context. Key strategies identified for future studies included the use of community health workers, smartphone application enhancement, and simpler and more frequent training for nurses, caregivers, and patients. Conclusions- A novel nurse-led, digital supported, caregiver-delivered stroke rehabilitation program did not improve patient physical functioning after stroke in rural China. Further stroke rehabilitation research suitable for resource-poor settings is required, with several components being suggested through stakeholder interviews in our study. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02247921.

16.
Int J Mol Sci ; 20(9)2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31085987

RESUMO

Sheepgrass (Leymus chinensis (Trin.) Tzvel.) is an economically and ecologically important forage in the grass family. Self-incompatibility (SI) limits its seed production due to the low seed-setting rate after self-pollination. However, investigations into the molecular mechanisms of sheepgrass SI are lacking. Therefore, microscopic observation of pollen germination and pollen tube growth, as well as transcriptomic analyses of pistils after self- and cross-pollination, were performed. The results indicated that pollen tube growth was rapidly inhibited from 10 to 30 min after self-pollination and subsequently stopped but preceded normally after cross-pollination. Time course comparative transcriptomics revealed different transcriptome dynamics between self- and cross-pollination. A pool of SI-related signaling genes and pathways was generated, including genes related to calcium (Ca2+) signaling, protein phosphorylation, plant hormone, reactive oxygen species (ROS), nitric oxide (NO), cytoskeleton, and programmed cell death (PCD). A putative SI response molecular model in sheepgrass was presented. The model shows that SI may trigger a comprehensive calcium- and phytohormone-dominated signaling cascade and activate PCD, which may explain the rapid inhibition of self-pollen tube growth as observed by cytological analyses. These results provided new insight into the molecular mechanisms of sheepgrass (grass family) SI.


Assuntos
Perfilação da Expressão Gênica/métodos , Poaceae/genética , Transcriptoma/genética , Cálcio/metabolismo , Flores/genética , Flores/fisiologia , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Polinização/genética , Polinização/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
17.
Int J Cardiovasc Imaging ; 35(9): 1615-1618, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31041634

RESUMO

Malignant peripheral nerve sheath tumors are rare sarcomas of children and adolescents, and they are aggressive tumors with a high rate of local recurrence. Here we report a case of a primary cardiac malignant peripheral nerve sheath tumor without neurofibromatosis type I. A 53-year old woman presented having had cough, expectoration, and dyspnea for 20 days and was found to have a heart-involving tumor diagnosed as a malignant peripheral nerve sheath tumor, a rare cardiac sarcoma of 9 × 4.5 × 3 cm in size. The patient underwent a successful resection of the tumor but died 14 months postoperative. We report this case for its rarity and peculiar mode of morphologic and immunohistochemical presentation.


Assuntos
Neoplasias Cardíacas , Neurofibrossarcoma , Biomarcadores Tumorais/análise , Biópsia , Procedimentos Cirúrgicos Cardíacos , Ecocardiografia , Evolução Fatal , Feminino , Neoplasias Cardíacas/química , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/cirurgia , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neurofibrossarcoma/química , Neurofibrossarcoma/diagnóstico por imagem , Neurofibrossarcoma/patologia , Neurofibrossarcoma/cirurgia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral
18.
Neurosci Lett ; 706: 24-29, 2019 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-31039427

RESUMO

Hostility is a common form of emotionally charged anger which can lead to maladaptive and unhealthy behaviors. Significant association between shortened telomeres and greater levels of hostility has been observed in civilian populations, but has not yet been comprehensively studied in military populations. Our study investigates the relationship between hostility, post-traumatic stress disorder (PTSD), and leukocyte telomere length (LTL) in a sample of United States Army Special Operations personnel (n = 474) who deployed to Iraq and/or Afghanistan as part of combat operations. Hostility was measured with five items from the Brief Symptom Inventory (BSI). PTSD was determined using the PTSD Checklist (PCL) total score. The LTL was assessed using quantitative polymerase chain reaction methods and regression analyses were conducted to determine the association of hostility and telomere length. PTSD subjects reported higher hostility scores compared with those without PTSD. Among the participants with PTSD, those with medium or high level of hostility had shorter LTL than those with low level hostility (P < 0.01). Stepwise regression indicated that hostility level and age, but not gender and PTSD, were negatively correlated with LTL. Univariate regression showed that total hostility score was negatively associated with LTL (CI= -0.06 to -0.002, Beta= -0.095, p < 0.039) as well as a significant correlation between LTL and hostility impulses (HI) (CI= -0.108 to -0.009, Beta= -0.106, p < 0.021) and hostility controlling (HC) (CI= -0.071 to -0.002, Beta= -0.095, p < 0.004). Multiple regression analyses revealed that, while HC has no significant association with LTL, HI was still negatively correlated with LTL (p = 0.021). Our data indicates that LTL is associated with HI levels. Prevention and treatment efforts designed to reduce hostility may help mitigate risk for LTL shortening, a process of cellular aging, and thus slow accelerated aged-related health outcomes.

19.
Molecules ; 24(10)2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31137649

RESUMO

In this study, a reliable and rapid method based on ultra high performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS) technology and MetabolitePilotMT software was developed for berberine metabolites identification in rat plasma. The chemical structures of the metabolites and their product ions were tentatively characterized or identified according to the molecular weights detected and MS/MS data. In all, nine metabolites, including M1 (demethyleneberberine, C19H18NO4, m/z 324), M2 (glucuronic acid-conjugated demethyleneberberine, C25H26NO10, m/z 500), M3 (diglucuronide-conjugated demethyleneberberine, C31H34NO16, m/z 676), M4 (glucuronic acid-conjugated jatrorrhizine or glucuronic acid-conjugated columbamine, C26H28NO10, m/z 514), M5 (berberrubine or thalifendine, C19H16NO4, m/z 322), M6 (glucuronic acid-conjugated berberrubine or glucuronic acid-conjugated thalifendine, C25H24NO10, m/z 498), M7 (sulfite-conjugated berberrubine or sulfite-conjugated thalifendine, C19H16NO7S, m/z 402), M8 (dihydroxy berberrubine or dihydroxy thalifendine, C19H16NO6, m/z 354) and M9 (dihydroxy berberine, C20H18NO6, m/z 368) were tentatively characterized or identified. Several new deposition patterns and three new metabolites (M7, M8 and M9) are reported in this paper for the first time. This work not only provides significant insights into the understanding of the metabolic pathways of berberine, but also contributes in identifying potential active drug candidates from the metabolites.

20.
Microb Pathog ; 131: 144-149, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30965088

RESUMO

Corynebacterium pseudotuberculosis (CP) infection in livestock has become highly difficult to control. To decrease the incidence of CP infection, the supplementation of feed with non-antibiotic antibacterial substances is a potential approach. The aim of this study was to assess the effects of sodium butyrate (NaB), a potential alternative to antibiotics, on CP infection in RAW264.7 macrophages and C57BL/6 mice. Our data showed that NaB (2 mM) significantly ameliorated CPinfection in RAW264.7 macrophages and decreased the bacterial load in the spleens of infected mice. By real-time PCR, we found that NaB induced significant decreases in zinc-dependent superoxide dismutase (sodC) and tip protein C (spaC) expression in CP from infected-RAW264.7 cells and in phospholipase D (pld) and spaC expression in CP from the spleens of infected mice. NaB treatment significantly up-regulated cathelicidin-related antimicrobial peptide (cramp) expression in spleens of mice infected with CP. Furthermore, NaB alleviated histopathological changes in spleens of CP-infected mice. In conclusion, NaB ameliorated CP infection in RAW264.7 macrophages and C57BL/6 mice, and these effects may be related to the modulation of sodC, spaC, pld, and cramp expression.


Assuntos
Ácido Butírico/farmacologia , Infecções por Corynebacterium/microbiologia , Corynebacterium pseudotuberculosis/efeitos dos fármacos , Corynebacterium pseudotuberculosis/patogenicidade , Macrófagos/efeitos dos fármacos , Células RAW 264.7/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/metabolismo , Carga Bacteriana/efeitos dos fármacos , Ácido Butírico/uso terapêutico , Modelos Animais de Doenças , Combinação de Medicamentos , Feminino , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Genes Bacterianos/genética , Camundongos , Camundongos Endogâmicos C57BL , Baço/microbiologia , Baço/patologia
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