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SooHyun Kim Zsuzsanna Barad Rachel Y. Cheong Istvn M. brahm 《Journal of neuroendocrinology》2020,32(1)
Rapid nonclassical effects of 17β‐oestradiol (E2) on intracellular signalling have been identified in the basal forebrain, although the extent to which these actions may be different in males and females is unknown. Previous work has shown that E2 rapidly phosphorylates cAMP responsive element binding protein (CREB) via ΕRα in female cholinergic neurones. Using this indicator, the present study examined whether nonclassical actions of E2 occur in a sexually dimorphic manner within basal forebrain cholinergic neurones in mice. In addition, we investigated the expression and intracellular distribution of oestrogen receptor (ΕR)α in cholinergic neurones in female and male mice. Animals were gonadectomised and treated 2 weeks later with E2. The number of CREB‐expressing cholinergic neurones was not altered in any of the brain regions after E2 treatment in both males and females. However, E2 treatment rapidly (< 15 minutes) increased (P < 0.05) the number of cholinergic neurones expressing phosphorylated CREB (pCREB) in the substantia innominata and medial septum but not in the striatum in female mice. By contrast, E2 did not change pCREB expression in cholinergic neurones in male mice at any time point (15 minutes, 1 hour, 4 hours), irrespective of the neuroanatomical location. We also observed that, in females, more cholinergic neurones expressed nuclear ΕRα in all regions, whereas males showed more cholinergic neurones with cytoplasmic or both nuclear and cytoplasmic expression of ΕRα. Taken together, these results demonstrate a marked sex difference in the E2‐induced nonclassical effect and intracellular distribution of ΕRα in basal forebrain cholinergic neurones in vivo. 相似文献
3.
Oncogenic Ras stimulates macropinocytosis, a clathrin-independent endocytosis that increases the uptake of extracellular fluid. However, the functional significance of and regulatory mechanisms driving macropinocytosis in cancer cells remain largely unknown. Here, we show that extracellular macromolecules, such as albumin, internalized by Ras-expressing cells can support growth and survival under the nutrient-deprived conditions like those found in tumors. Moreover, we demonstrate that autophagy, a lysosome-mediated catabolic pathway, is required for the uptake and degradation of macropinocytic vesicles. Intracellular metabolites derived from macropinocytosis and autophagy directly influence the activity and localization of mTOR, which is ultimately responsible for the restoration of cell growth. Surprisingly, suppression of mTORC1, which typically triggers anabolic processes, facilitates macropinocytosis and thus supports cell growth and survival under the nutrient-deprived conditions. In a mouse xenograft model of pancreatic ductal adenocarcinoma, concomitant inhibition of macropinocytosis/autophagy and mTOR activity resulted in antitumor effects. These data suggest that novel anti-cancer strategies interrupting these metabolic processes and related signaling molecules may represent promising therapeutic avenues. 相似文献
4.
Kee Thai Yeo Ju Lee Oei Daniele De Luca Georg M. Schmölzer Robert Guaran Pamela Palasanthiran Kishore Kumar Giuseppe Buonocore Jeanie Cheong Louise S. Owen Satoshi Kusuda Jennifer James Gina Lim Ankur Sharma Sabita Uthaya Christopher Gale Elizabeth Whittaker Cheryl Battersby Neena Modi Mikael Norman Lars Naver Eric Giannoni Yenge Diambomba Prakeshkumar S. Shah Luigi Gagliardi Michael Harrison Shakti Pillay Abdullah Alburaey Yuan Yuan Huayan Zhang 《Acta paediatrica (Oslo, Norway : 1992)》2020,109(11):2192-2207
5.
Kreins Alexandra Y. Velasco Helena F. Cheong Kai-Ning Rao Kanchan Veys Paul Worth Austen Gaspar H. Bobby Booth Claire 《Journal of clinical immunology》2022,42(1):94-107
Journal of Clinical Immunology - Unconditioned hematopoietic stem cell transplantation (HSCT) is the recommended treatment for patients with adenosine deaminase (ADA)-deficient severe combined... 相似文献
6.
Background
Lifestyle, in particular obesity and smoking has significant impacts on fertility and an important focus for the treatment of reproductive failures is the optimisation of periconceptional lifestyle behaviours. The preimplantation intrauterine environment within the uterus is also key for embryo development and early programming. Although the benefits a healthy periconceptional lifestyle are well described, there remains a paucity of data demonstrating the efficacy of interventions designed to optimise preconceptional lifestyle behaviours and choices.Methods
This study is a prospective randomised controlled trial which aims to address the question of whether an online personalised lifestyle coaching application is an effective means of delivering periconceptional advice in women suffering from reproductive failures. Women suffering from subfertility or recurrent miscarriages attending the outpatient clinic will be randomised into either the intervention arm (personalised online lifestyle coaching application) or the control arm (standard periconceptional advice including information from NHS websites). Both groups will be asked to complete a validated lifestyle questionnaire at baseline, and 6, 12, 18 and 24?weeks after randomisation. The primary outcome is the composite dietary and lifestyle risk score at 12?weeks. The secondary outcomes will include compliance with the program, proportion achieving spontaneous conception during the study period and the dietary and lifestyle risk score at 24?weeks.Discussion
With this study, we aim to clarify whether a personalised online based lifestyle coaching application is more effective at improving behaviours than standard advice offered by National Health Service (NHS) resources. A personalised lifestyle coaching application may represent an empowering and cost effective means of delivering periconceptional advice in women with subfertility or recurrent miscarriages.Trial registration
The iPLAN trial was retrospectively registered (ISRCTN 89523555).7.
Head and neck cancer is becoming a more recognizable pathology to the general population and dentists. The modes of treatment include surgery and/or radiation therapy. Where possible, pretreatment dental assessment shall be provided for these patients before they undergo radiation therapy. There are occasions, however, whereby head and neck cancer patients are not prepared optimally for radiation therapy. Because of this, they succumb to complicated oral complications after radiation therapy. The management of xerostomia has been reviewed in Part I of this series. In this article, the management of dental caries, a sequalae of xerostomia following radiation therapy is reviewed. 相似文献
8.
Head and neck cancer is becoming a more recognizable pathology to the general population and dentists. The modes of treatment include surgery and/or radiation therapy. Where possible, pretreatment dental assessment shall be provided for these patients before they undergo radiation therapy. There are occasions, however, whereby head and neck cancer patients are not prepared optimally for radiation therapy. Because of this, they succumb to complicated oral adverse effects after radiation therapy. The second last part of this series reviews and discusses the management of complication that commonly occur to the oral mucosa, i.e. mucositis. 相似文献
9.
Unintended intravascular injection from inferior alveolar nerve blocks can result in frustrating distant complications affecting such structures as the middle ear and eyes. Possible complications affecting the eyes include blurring of vision, diplopia, mydriasis, palpebral ptosis and amaurosis (temporary or permanent). In this article, we present a complication that has been reported only rarely. Two patients developed transient loss of power of accommodation of the eye resulting in blurred vision after routine inferior alveolar nerve blocks on the ipsilateral side. Clear vision returned within 10-15 minutes after completion of the blocks. The possible explanation for this phenomenon is accidental injection into the neurovascular bundle of local anesthetic agents, which were carried via the blood to the orbital region. This resulted in paralysis of a branch of cranial nerve III, the short ciliary nerves that innervate the ciliary muscle, which controls accommodation. 相似文献
10.