排序方式: 共有130条查询结果,搜索用时 15 毫秒
21.
Robin M. Voigt Christopher B. Forsyth Stefan J. Green Ece Mutlu Phillip Engen Martha H. Vitaterna Fred W. Turek Ali Keshavarzian 《PloS one》2014,9(5)
Intestinal dysbiosis and circadian rhythm disruption are associated with similar diseases including obesity, metabolic syndrome, and inflammatory bowel disease. Despite the overlap, the potential relationship between circadian disorganization and dysbiosis is unknown; thus, in the present study, a model of chronic circadian disruption was used to determine the impact on the intestinal microbiome. Male C57BL/6J mice underwent once weekly phase reversals of the light:dark cycle (i.e., circadian rhythm disrupted mice) to determine the impact of circadian rhythm disruption on the intestinal microbiome and were fed either standard chow or a high-fat, high-sugar diet to determine how diet influences circadian disruption-induced effects on the microbiome. Weekly phase reversals of the light:dark (LD) cycle did not alter the microbiome in mice fed standard chow; however, mice fed a high-fat, high-sugar diet in conjunction with phase shifts in the light:dark cycle had significantly altered microbiota. While it is yet to be established if some of the adverse effects associated with circadian disorganization in humans (e.g., shift workers, travelers moving across time zones, and in individuals with social jet lag) are mediated by dysbiosis, the current study demonstrates that circadian disorganization can impact the intestinal microbiota which may have implications for inflammatory diseases. 相似文献
22.
Ulrike Schoetz Diana Klein Julia Hess Seyd Shnayien Steffen Spoerl Michael Orth Samet Mutlu Roman Hennel Anja Sieber Ute Ganswindt Benedikt Luka Andreas R. Thomsen Kristian Unger Verena Jendrossek Horst Zitzelsberger Nils Blüthgen Claus Belka Steffen Unkel Bertram Klinger Kirsten Lauber 《Cell death & disease》2021,12(12)
Resistance against radio(chemo)therapy-induced cell death is a major determinant of oncological treatment failure and remains a perpetual clinical challenge. The underlying mechanisms are manifold and demand for comprehensive, cancer entity- and subtype-specific examination. In the present study, resistance against radiotherapy was systematically assessed in a panel of human head-and-neck squamous cell carcinoma (HNSCC) cell lines and xenotransplants derived thereof with the overarching aim to extract master regulators and potential candidates for mechanism-based pharmacological targeting. Clonogenic survival data were integrated with molecular and functional data on DNA damage repair and different cell fate decisions. A positive correlation between radioresistance and early induction of HNSCC cell senescence accompanied by NF-κB-dependent production of distinct senescence-associated cytokines, particularly ligands of the CXCR2 chemokine receptor, was identified. Time-lapse microscopy and medium transfer experiments disclosed the non-cell autonomous, paracrine nature of these mechanisms, and pharmacological interference with senescence-associated cytokine production by the NF-κB inhibitor metformin significantly improved radiotherapeutic performance in vitro and in vivo. With regard to clinical relevance, retrospective analyses of TCGA HNSCC data and an in-house HNSCC cohort revealed that elevated expression of CXCR2 and/or its ligands are associated with impaired treatment outcome. Collectively, our study identifies radiation-induced tumor cell senescence and the NF-κB-dependent production of distinct senescence-associated cytokines as critical drivers of radioresistance in HNSCC whose therapeutic targeting in the context of multi-modality treatment approaches should be further examined and may be of particular interest for the subgroup of patients with elevated expression of the CXCR2/ligand axis.Subject terms: Radiotherapy, Head and neck cancer, Senescence, Tumour heterogeneity 相似文献
23.
Arican N Kaya M Kalayci R Uzun H Ahishali B Bilgic B Elmas I Kucuk M Gurses C Uzun M 《Life sciences》2006,79(1):1-7
We investigated the effects of lipopolysachharide (LPS) on functional and structural properties of the blood-brain barrier (BBB) during pentylenetetrazole (PTZ)-induced epileptic seizures in rats. Arterial blood pressure was significantly elevated during epileptic seizures irrespective of LPS pretreatment. Plasma levels of interleukin (IL)-1, interleukin (IL)-6, nitric oxide (NO) and malondialdehyde (MDA) increased while catalase concentrations decreased in animals treated with LPS, PTZ and LPS plus PTZ. The significantly increased BBB permeability to Evans blue (EB) dye in the cerebral cortex, diencephalon and cerebellum regions of rats by PTZ-induced seizures was markedly reduced upon LPS pretreatment. Immunoreactivity for tight junction proteins, zonula occludens-1 and occludin, did not change in brain vessels of animals treated with PTZ and LPS plus PTZ. Glial fibrillary acidic protein immunoreactivity was increased in LPS, but not in PTZ and LPS plus PTZ. These results indicate that LPS pretreatment reduces the passage of EB dye bound to albumin into the brain, at least partly, by increasing plasma NO and IL-6 levels during PTZ-induced epileptic seizures. We suggest that LPS may provide protective effects on the BBB integrity during epileptic seizures through transcellular pathway, since the paracellular route remained unaffected by LPS and LPS plus PTZ. 相似文献
24.
Recent studies have shown that learning and memory capacity is disturbed in depressive patients, and it is important to reveal the effects of antidepressant drugs on cognitive function in depressive patients with memory problems. Citalopram, a selective serotonin reuptake inhibitor (SSRI), is one of the most widely used drugs for the treatment of disorders related to serotonergic dysfunction like depression and anxiety. Contradictory findings exist regarding the effects of SSRIs on memory. The aim of this study is to investigate whether citalopram affects memory in various models of learning and memory tasks in rats. Citalopram (at 20 and 50 mg/kg) significantly shortened the retention latency in the passive avoidance test and prolonged the transfer latency on the second day at 10 and 50 mg/kg doses in the elevated plus-maze test. Citalopram also significantly increased the number of errors (at the 10 mg/kg dose) and prolonged the latency values compared to the control group in both reference and working memory trials in the three-panel runway test. Citalopram also impaired reference memory trials of animals at the 20 mg/kg dose. In conclusion, citalopram impaired cognitive performance in passive avoidance, elevated plus-maze and three-panel runway tasks in naive rats. These effects might be related to serotonergic and nitrergic mechanisms, which need to be investigated in further studies. 相似文献
25.
Kathryn A. Radigan Luisa Morales-Nebreda Saul Soberanes Trevor Nicholson Recep Nigdelioglu Takugo Cho Monica Chi Robert B. Hamanaka Alexander V. Misharin Harris Perlman G. R. Scott Budinger G?khan M. Mutlu 《PloS one》2014,9(9)
Rationale
During the recent H1N1 outbreak, obese patients had worsened lung injury and increased mortality. We used a murine model of influenza A pneumonia to test the hypothesis that leptin receptor deficiency might explain the enhanced mortality in obese patients.Methods
We infected wild-type, obese mice globally deficient in the leptin receptor (db/db) and non-obese mice with tissue specific deletion of the leptin receptor in the lung epithelium (SPC-Cre/LepRfl/fl) or macrophages and alveolar type II cells (LysM-Cre/Leprfl/fl) with influenza A virus (A/WSN/33 [H1N1]) (500 and 1500 pfu/mouse) and measured mortality, viral clearance and several markers of lung injury severity.Results
The clearance of influenza A virus from the lungs of mice was impaired in obese mice globally deficient in the leptin receptor (db/db) compared to normal weight wild-type mice. In contrast, non-obese, SP-C-Cre+/+/LepRfl/fl and LysM-Cre+/+/LepRfl/fl had improved viral clearance after influenza A infection. In obese mice, mortality was increased compared with wild-type mice, while the SP-C-Cre+/+/LepRfl/fl and LysM-Cre+/+/LepRfl /fl mice exhibited improved survival.Conclusions
Global loss of the leptin receptor results in reduced viral clearance and worse outcomes following influenza A infection. These findings are not the result of the loss of leptin signaling in lung epithelial cells or macrophages. Our results suggest that factors associated with obesity or with leptin signaling in non-myeloid populations such as natural killer and T cells may be associated with worsened outcomes following influenza A infection. 相似文献26.
27.
Response surface methodology was applied to determine the effects of pullulanase debranching, microwave irradiation time (2–4 min) and power (20–100%) on resistant starch (RS) formation and in-vitro glycemic index (GI) values in high amylose corn starch, Hylon VII. Starch:water (1:10) suspensions were cooked and autoclaved, debranched with pullulanase (1000 PUN/g; 1500 U/kg starch) at 60 °C and then different microwave-storing cycles and drying (oven or freeze drying) processes were applied. In order to describe the relationship between the dependent and independent variables (microwave power and irradiation time), the response values were fitted by first order polynomial regression models. Significance analysis showed that microwave irradiation time had significant effect on RS content and GI value of the samples treated with one cycle of microwave-storing prior to freeze-drying. Microwave power had significant factor on the GI value of the samples that were oven-dried after one cycle of microwave-storing. Solubility and water binding capacity values of all heat treated samples were higher than those of native starch. On the other hand, RVA viscosity values were lower than native starch for oven-dried samples. Water binding capacity, solubility and final viscosity values of the freeze-dried samples were higher than those of oven-dried ones. 相似文献
28.
Mehmet Mutlu Nazan Turhan Meral T. Ercan Ahmet R. Özdural Serdar S. Çelebi 《Biotechnology Techniques》1996,10(2):71-76
Summary Surface of polystyrene beads was modified by poly(phe-lys) for invertase immobilisation. The optimum immobilisation conditions of invertase were; 0.01% (w/v) poly(phe-lys), 2% (v/v) glutaraldehyde at 25 °C and pH 4.5. The kinetics of sucrose hydrolysis by free and immobilised invertase in a batch reactor at pH 4.5 and 55 °C gave Km and Vmax values for sucrose with free and immobilised invertase of 81, 114 mM and 10.1, 9.2 mol glucose/min.mg enzyme, respectively. The deactivation rate constants of free and immobilised invertase were 0.0347 and 0.0098 min–1, respectively. 相似文献
29.
N. Başaran Mutlu Ağardan Zelihagül Değim Şükran Yılmaz Levent Altıntaş Turgut Topal 《AAPS PharmSciTech》2016,17(4):968-977
Liposome (spherical vesicles) and cochleate (multilayer crystalline, spiral structure) formulations containing raloxifene have been developed having dimethyl-β-cyclodextrin (DM-β-CD) or sodium taurocholate (NaTC). Raloxifene was approved initially for the treatment of osteoporosis but it is also effective on breast tissue and endometrial cells. Raloxifene inhibits matrix metalloproteinase-2 (MMP-2) enzyme, which is known to be responsible for tumor invasion and the initiation of angiogenesis during the tumor growth. Therefore, raloxifene was selected as a model drug. A series of raloxifene-loaded liposome and cochleate formulations were prepared. In vitro release studies and in vivo tests were performed. Breast cancer cell lines (MCF-7) were also used to find the most effective formulation. Highest antitumor activity was observed, and MMP-2 enzyme was also found to be inhibited with raloxifene-loaded cochleates containing DM-β-CD. These developed formulations can be helpful for further treatment alternatives and new strategies for cancer therapy. 相似文献
30.
Endometrial stem cell transplantation in MPTP‐ exposed primates: an alternative cell source for treatment of Parkinson's disease
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Erin F. Wolff Levent Mutlu Efi E. Massasa John D. Elsworth D. Eugene Redmond Jr. Hugh S. Taylor 《Journal of cellular and molecular medicine》2015,19(1):249-256
Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra. Cell‐replacement therapies have emerged as a promising strategy to slow down or replace neuronal loss. Compared to other stem cell types, endometrium‐derived stem cells (EDSCs) are an attractive source of stem cells for cellular therapies because of their ease of collection and vast differentiation potential. Here we demonstrate that endometrium‐derived stem cells may be transplanted into an MPTP exposed monkey model of PD. After injection into the striatum, endometrium‐derived stem cells engrafted, exhibited neuron‐like morphology, expressed tyrosine hydroxylase (TH) and increased the numbers of TH positive cells on the transplanted side and dopamine metabolite concentrations in vivo. Our results suggest that endometrium‐derived stem cells may provide a therapeutic benefit in the primate model of PD and may be used in stem cell based therapies. 相似文献