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排序方式: 共有297条查询结果,搜索用时 15 毫秒
291.
Noman MZ Janji B Kaminska B Van Moer K Pierson S Przanowski P Buart S Berchem G Romero P Mami-Chouaib F Chouaib S 《Cancer research》2011,71(18):5976-5986
The relationship between hypoxic stress, autophagy, and specific cell-mediated cytotoxicity remains unknown. This study shows that hypoxia-induced resistance of lung tumor to cytolytic T lymphocyte (CTL)-mediated lysis is associated with autophagy induction in target cells. In turn, this correlates with STAT3 phosphorylation on tyrosine 705 residue (pSTAT3) and HIF-1α accumulation. Inhibition of autophagy by siRNA targeting of either beclin1 or Atg5 resulted in impairment of pSTAT3 and restoration of hypoxic tumor cell susceptibility to CTL-mediated lysis. Furthermore, inhibition of pSTAT3 in hypoxic Atg5 or beclin1-targeted tumor cells was found to be associated with the inhibition Src kinase (pSrc). Autophagy-induced pSTAT3 and pSrc regulation seemed to involve the ubiquitin proteasome system and p62/SQSTM1. In vivo experiments using B16-F10 melanoma tumor cells indicated that depletion of beclin1 resulted in an inhibition of B16-F10 tumor growth and increased tumor apoptosis. Moreover, in vivo inhibition of autophagy by hydroxychloroquine in B16-F10 tumor-bearing mice and mice vaccinated with tyrosinase-related protein-2 peptide dramatically increased tumor growth inhibition. Collectively, this study establishes a novel functional link between hypoxia-induced autophagy and the regulation of antigen-specific T-cell lysis and points to a major role of autophagy in the control of in vivo tumor growth. 相似文献
292.
Rask-Andersen M Jacobsson JA Moschonis G Chavan RA Sikder MA Allzén E Alsiö J Chrousos GP Manios Y Fredriksson R Schiöth HB 《European journal of human genetics : EJHG》2012,20(2):192-197
Genome-wide association studies have shown a strong association of single-nucleotide polymorphisms (SNPs) in the near vicinity of the TMEM18 gene. The effects of the TMEM18-associated variants are more readily observed in children. TMEM18 encodes a 3TM protein, which locates to the nuclear membrane. The functional context of TMEM18 and the effects of its associated variants are as of yet undetermined. To further explore the effects of near-TMEM18 variants, we have genotyped two TMEM18-associated SNPs, rs6548238 and rs4854344, in a cohort of 2352 Greek children (Healthy Growth Study). Included in this study are data on anthropomorphic traits body weight, BMI z-score and waist circumference. Also included are dietary energy and macronutrient intake as measured via 24-h recall interviews. Major alleles of rs6548238 and rs4854344 were significantly associated with an increased risk of obesity (odds ratio = 1.489 (1.161-1.910) and 1.494 (1.165-1.917), respectively), and positively correlated to body weight (P = 0.017, P = 0.010) and waist circumference (P = 0.003, P = 0.003). An association to energy and macronutrient intake was not observed in this cohort. We also correlated food intake and body weight in a food choice model in rats to Tmem18 expression in central regions involved in feeding behavior. We observed a strong positive correlation between TMEM18 expression and body weight in the prefrontal cortex (PFC) (r = 0.5694, P = 0.0003) indicating a potential role for TMEM18 in higher functions related to feeding involving the PFC. 相似文献
293.
M. Oliur Rahman Ali S. Alqahtani Sayma Binte Huda Shah Alam Siddiqui Omar M. Noman Fahd Nasr Md. Abul Hassan Sheikh Nazrul Islam 《Pharmaceutical biology》2021,59(1):1056
ContextStreblus asper Lour. (Moraceae) is used for the treatment of different ailments, including diabetes, and requires scientific validation.ObjectiveThe study evaluates antidiabetic effects, antioxidant potential, and cytotoxicity of leaf and bark extracts of S. asper.Materials and methodsAntidiabetic effects were assessed by inducing diabetes in Wistar albino rats (n = 5, six groups included 30 rats) by injecting alloxan [0.25 mg/kg body weight (bw)] intraperitoneally, and efficacy of methanol extracts of leaf and bark, and aqueous extract of leaves were evaluated by oral administration of 300 mg/kg bw of extracts for 3 weeks. Glibenclamide (Dibenol™) was used as a control (10 mg/kg bw). Antioxidant properties were examined by DPPH free radical scavenging activity, and cytotoxicity was investigated using a brine shrimp lethality assay.ResultsMethanol extracts of leaves and bark, and the aqueous extract of leaves of S. asper, caused significant reductions in blood glucose levels in diabetic rats of 36.83, 70.33, and 52.71%, respectively, after 21 days of treatment. IC50 values in DPPH radical scavenging assessment for those extracts were 58.92, 88.54, and 111.36 µg/mL, respectively. LC50 values for brine shrimp lethality for the extracts were 173.80, 32.36, and 3235.9 µg/mL, respectively.Discussion and conclusionsThe methanol bark extract of S. asper showed significant antidiabetic activity. This study will significantly contribute to establishing the plant as an alternative medicinal resource for rural populations of Bangladesh and provides an opportunity for further research to identify the primary active compound(s) and establish new drug candidates. 相似文献
294.
295.
Jargalsaikhan Dagvadorj Yoshikazu Naiki Gantsetseg Tumurkhuu Abu Shadat Mohammod Noman Imtiaz Iftakhar‐E‐Khuda Takayuki Komatsu Naoki Koide Tomoaki Yoshida Takashi Yokochi 《Immunology》2010,129(1):97-104
The regulatory role of tumour necrosis factor‐α (TNF‐α) on the expression of suppressor of cytokine signalling 3 (SOCS‐3) in response to lipopolysaccharide (LPS) was examined using peritoneal macrophages from TNF‐α‐deficient mice. The LPS‐induced SOCS‐3 expression was markedly augmented in macrophages from wild‐type mice whereas such augmentation was not seen in the cells from TNF‐α‐deficient mice. However, there was no significant difference in the level of SOCS‐3 messenger RNA expression between macrophages from wild‐type mice and those from TNF‐α‐deficient mice. The addition of exogenous TNF‐α augmented the LPS‐induced SOCS‐3 expression in macrophages from TNF‐α‐deficient mice. The pulse chase analysis suggested augmented degradation of LPS‐induced SOCS‐3 protein in macrophages from TNF‐α‐deficient mice. Moreover, MG 132, a 26S proteasome inhibitor, sustained the LPS‐induced SOCS‐3 expression in those cells. The tyrosine phosphorylation of SOCS‐3 was definitely induced in LPS‐stimulated macrophages from TNF‐α‐deficient mice but not wild‐type mice. A tyrosine phosphatase inhibitor enhanced the tyrosine phosphorylation of SOCS‐3 in wild‐type mice and accelerated the degradation. Therefore, it was suggested that TNF‐α prevented the degradation of SOCS‐3 protein via inhibition of the tyrosine phosphorylation in LPS‐stimulated macrophages. 相似文献
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297.