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glucocorticoid receptor signaling in the brain and its involvement in cognitive function

Neural Regeneration Research 2025年第9期20卷 2520-2537页

作者： Chonglin Su Taiqi Huang Meiyu Zhang Yanyu Zhang Yan Zeng Xingxing Chen Brain Science and Advanced Technology Institute Hubei Province Key Laboratory of Occupational Hazard Identification and ControlSchool of MedicineWuhan University of Science and TechnologyWuhanHubei ProvinceChina

The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental *** the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and *** glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic *** interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive *** appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive *** with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor *** review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive *** emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive *** provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.

关键词： brain-derived neurotrophic factor calcium signaling glucocorticoid receptor glucocorticoid glutamate transmission hypothalamic-pituitary-adrenal axis long-term potentiation neurocognitive disorders neuroplasticity stress

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glucocorticoid reduces the efficacy of afatinib on the head and neck squamous cell carcinoma

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BIOCELL 2023年第2期47卷 329-338页

作者： DONGYANG WANG YI CHEN JING HUANG YOU ZHANG CHONGKUI SUN YINGQIANG SHEN State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesChinese Academy of Medical Sciences Research Unit of Oral Medicine of Carcinogenesis and ManagementWest China Hospital of StomatologySichuan UniversityChengdu610041China

glucocorticoids(GC)are widely used to counter the adverse events during cancer therapy;nonetheless,previous studies pointed out that GC may reduce the efficacy of chemotherapy on cancer cells,especially in epidermal growth factor receptor(EGFR)-targeted therapy of head and neck squamous cell carcinoma(HNSCC)remaining to be *** primary aim of the present study was to probe into the GC-induced resistance of EGFR-targeted drug afatinib and the underlying *** cell lines(HSC-3,SCC-25,SCC-9,and H-400)and the human oral keratinocyte(HOK)cell lines were assessed for GC receptor(GR)*** promoting tumor growth effect of GC was evaluated by the CCK-8 assay and flow *** of signaling pathways participants GR,mTOR,and EGFR were determined by quantitative polymerase chain reaction and western *** increased the proliferation of HNSCC cells in a GR-dependent manner and promoted AKT/mTOR *** GC failed in counteracting the inhibition of rapamycin in the mTOR signaling ***,GC also induced resistance to EGFR-targeted drug afatinib through AKT/mTOR instead of the EGFR/ERK signaling ***,GCs reduce the efficacy of afatinib on HNSCC,implicating a cautious use of glucocorticoids in clinical practice.

关键词： glucocorticoid Head and neck squamous cell carcinoma Afatinib EGFR Targeted therapy mTOR

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Signal transduction pathway of glucocorticoid's rapid action in PC12 cells

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Chinese Science Bulletin 1999年第20期44卷 1837-1843页

作者： Jian Qiu Shujie Lou Yizhang Chen Neuroscience Research Institute Second Military Medical University Shanghai China

Traditionally, steroid hormone action has been described as the modulation of nuclear transcription, thus triggering genomic events that are responsible for physiological effects. Despite early observation of rapid steroid effects that were incompatible with this theory, nonge-nomic steroid action has been widely recognized only recently. More and more evidence for these rapid effects has been reported in recent years, but the signal transduction pathways

关键词： PC12 cells glucocorticoid nongenomic signal transduction.

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glucocorticoid receptor regulates expression of microRNA-22 and downstream signaling pathway in apoptosis of pancreatic acinar cells

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World Journal of Gastroenterology 2018年第45期24卷 5120-5130页

作者： Qiang Fu Chuan-Jiang Liu Xu Zhang Zhen-Sheng Zhai Yu-Zhu Wang Ming-Xing Hu Xian-Ling Xu Hong-Wei Zhang Tao Qin Department of Hepatobiliary and Pancreatic Surgery People’s Hospital of Zhengzhou University (Henan Provincial People’s Hospital) School of Medicine Zhengzhou University

AIM To elucidate the underlying mechanism that microRNA-22(miR-22) promotes the apoptosis of rat pancreatic acinar cells(AR42 J) and the elements that regulate the expression of *** One hundred nanomoles per liter of caerulein(Cae)was administrated to induce the apoptosis of AR42 J cells and the apoptosis rate was detected by flow cytometry analysis. An amylase assay kit was used to measure the amylase expression level in the supernatant. Quantitative real-time PCR(qRT-PCR)was adopted to measure miR-22 expression. We used online tools to predict the potential transcription promoter of miR-22 and the binding sites, which was further identified by using luciferase reporter analysis,chromatin immunoprecipitation(ChIP) and ChIPqP CR assays. Then, a mimic of miR-22, Nr3 c1 plasmid encoding the glucocorticoid receptor(GR), and siNr3 c1 were used to transfect AR42 J cells, *** mRNA expression of miR-22, Nr3 c1, and Erb-b2 receptor tyrosine kinase 3(ErbB3) was confirmed by qRT-PCR and the apoptosis rate of AR42 J cells was detected by flow cytometry analysis. Western blot was used to detect the expression of ErbB3, GR, PI3 k, PI3 kp85α, Akt, p-Akt, Bad, Bax, Bcl-xl, Bcl-2, and cleaved *** After inducing apoptosis of AR42 J cells in vitro, the expression of miR-22 was significantly increased by2.20 ± 0.26 and 4.19 ± 0.54 times, respectively, at3 h and 6 h in comparison with the control *** revealed by qRT-PCR assay, the expression of miR-22 was 78.25 ± 6.61 times higher in the miR-22 mimic group relative to the miRNA control group,accompanied with an obviously increased acinar cell apoptosis rate(32.53 ± 1.15 vs 18.07 ± 0.89, P =0.0006). The upregulation of miR-22 could suppress its target gene, ErbB3, and the phosphorylation of PI3 k and Akt. Furthermore, we predicted the potential transcription promoter of miR-22 and the binding sites using online tools. Luciferase reporter analysis and sitedirected mutagenesis indicated that the b

关键词： MicroRNA-22 Apoptosis Pancreatic acinar cells Erb-b2 receptor tyrosine kinase 3 glucocorticoid receptor

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glucocorticoid pulse therapy in an elderly patient with post-COVID-19 organizing pneumonia:A case report

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World Journal of Clinical Cases 2023年第17期11卷 4152-4158页

作者： Shinhee Park Youngeun Jang So-My Koo Bo Da Nam Hee-Young Yoon Division of Allergy and Pulmonary Medicine Department of Internal MedicineSoonchunhyang University Bucheon HospitalBucheon 14584South Korea Division of Allergy and Respiratory Diseases Department of Internal MedicineSoonchunhyang University Seoul HospitalSeoul 04401South Korea Department of Radiology Soonchunhyang University Seoul HospitalSeoul 04401South Korea

BACKGROUND Pulmonary fibrosis often occurs as a sequel of coronavirus disease 2019(COVID-19);however,in some cases,it can rapidly progress,similar to the acute exacerbation of interstitial lung *** are the standard treatment for severe COVID-19 pneumonia requiring oxygen supply;however,the post-COVID-19 efficacy of high-dose steroid therapy remains ***,we presented a case of an 81-year-old man who developed acute respiratory failure after COVID-19 and was treated with glucocorticoid pulse *** SUMMARY An 81-year-old man with no respiratory symptoms was admitted due to a diabetic *** had been previously treated for COVID-19 pneumonia six weeks ***,upon admission,he suddenly complained of dyspnea and required a high-flow oxygen *** simple chest radiography and computed tomography(CT)revealed diffuse ground-glass opacities and consolidation in both ***,repeated sputum tests did not identify any infectious pathogens,and initial broad-spectrum antibiotic therapy did not result in any clinical improvement with the patient having an increasing oxygen *** patient was diagnosed with post-COVID-19 organizing ***,we initiated glucocorticoid pulse therapy of 500 mg for three days followed by a tapered dose on hospital day(HD)*** three days of pulse treatment,the patient's oxygen demand *** patient was subsequently discharged on HD 41,and chest radiography and CT scans have almost normalized nine months after *** glucocorticoid pulse therapy may be considered when the usual glucocorticoid dose is ineffective for patients with COVID-19 sequelae.

关键词： Coronavirus glucocorticoid Lung disease Interstitial Organizing pneumonia Case report

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glucocorticoid-induced thrombotic microangiopathy in paroxysmal nocturnal hemoglobinuria:A case report and review of literature

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World Journal of Clinical Cases 2023年第8期11卷 1799-1807页

作者： Xiao-Dong Yang Bo Ju Jia Xu Nuan-Nuan Xiu Xiao-Yun Sun Xi-Chen Zhao Department of Hematology The Central Hospital of Qingdao West Coast New AreaQingdao 266555Shandong ProvinceChina

BACKGROUND Thrombotic microangiopathy(TMA)is a group of disorders that converge on excessive platelet aggregation in the microvasculature,leading to consumptive thrombocytopenia,microangiopathic hemolysis and ischemic end-organ *** predisposed patients,TMA can be triggered by many environmental ***(GCs)can compromise the vascular ***,GC-associated TMA has rarely been reported,which may be due to the lack of awareness of *** the high frequency of thrombocytopenia during GC treatment,particular attention should be given to this potentially fatal *** SUMMARY An elderly Chinese man had a 12-year history of aplastic anemia(AA)and a 3-year history of paroxysmal nocturnal hemoglobinuria(PNH).Three months earlier,methylprednisolone treatment was initiated at 8 mg/d and increased to 20 mg/d to alleviate complement-mediated *** GC treatment,his platelet counts and hemoglobin levels rapidly *** admission to our hospital,the dose of methylprednisolone was increased to 60 mg/d in an attempt to enhance the suppressive ***,increasing the GC dose did not alleviate hemolysis,and his cytopenia *** evaluation of the marrow smears revealed increased cellularity with an increased percentage of erythroid progenitors without evident *** of differentiation(CD)55 and CD59 expression was significantly decreased on erythrocytes and *** the following days,platelet transfusion was required due to severe *** of platelet transfusion refractoriness indicated that the exacerbated cytopenia may have been caused by the development of TMA due to GC treatment because the transfused platelet concentrates had no defects in glycosylphosphatidylinositol-anchored *** examined blood smears and found a small number of schistocytes,dacryocytes,acanthocytes and target *** of GC treatment resulted in rapidl

关键词： Aplastic anemia Paroxysmal nocturnal hemoglobinuria glucocorticoid Methylprednisolone Thrombotic microangiopathy Platelet transfusion refractoriness Case report

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The protective effect of icariin on glucocorticoid-damaged BMECs explored by microfluidic organ chip

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Chinese Chemical Letters 2022年第6期33卷 3177-3182页

作者： Tengqi Li Qingyu Zhang Fuqiang Gao Yadi Liu Wei Sun Yiyang Dong Department of Orthopedics Peking University China-Japan Friendship School of Clinical MedicineBeijing 100029China Department of Orthopedics Peking University Shougang HospitalBeijing 100144China Department of Orthopedics Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJi’nan 250021China Department of Orthopedics China-Japan Friendship HospitalBeijing 100029China Office of Academic Affairs Beijing University of Chemical TechnologyBeijing 100029China Department of Pharmaceutical Analysis College of Life Science and TechnologyBeijing University of Chemical TechnologyBeijing 100029China

Osteonecrosis of the femoral head(ONFH)is a devastating musculoskeletal disease characterized by the impaired circulation of *** purpose of this study was to explore the underlying mechanisms of the protective effect of icariin on the glucocorticoid-induced injury of bone microvascular endothelial cells(BMECs).Normal BMECs were extracted from the femoral heads by enzymatic isolation and magneticactivated cell sorting *** and icariin were used to intervene BMECs in microfluidic organ chips,and phalloidin staining was conducted to observe the cell morphology and *** next-generation transcriptome sequencing and real-time quantitative reverse transcription-polymerase chain reaction(q RT-PCR)were performed to identify the differentially expressed genes(DEGs)in different *** the microfluidic organ chip,it can be observed that after dexamethasone intervention,the filamentous structure in cell fibers disappeared and the cell morphology changed from spindle to round until *** could relieve these changes and showed a protective effect on glucocorticoiddamaged *** addition,201 DEGs were detected between the icariin protection group and the dexamethasone group,which were significantly enriched in 17 signaling pathways.8 of the top ten selected hub genes(IL6,PTGS2,VEGFA,etc.)were confirmed by q *** factors(TFs)-gene network showed 63 connections between 18 TFs and 12 *** instance,GATA2 could regulate 5 *** associations between 92 mi RNA and 12 DEGs were visualized in a mi RNA-gene *** hub mi RNA,has-mir-335–5 p was predicted to interact with 8 DEGs(PTGS2,VEGFA,etc.).Microfluidic organ chips could provide excellent morphological results for cell experiments,by which it could be observed that icariin showed a protective effect on the glucocorticoid-induced injury of ***,these DEGs,possible regulatory TF(GATA2,FOXC1,etc.)and mi RNA(has-mir-335–5 p)might be dysregulated in the ini

关键词： Osteonecrosis of the femoral head Bone microvascular endothelial cells glucocorticoid Microfluidic chip Bioinformatic analysis

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glucocorticoid reduction induced chorea in pediatric-onset systemic lupus erythematosus:A case report

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World Journal of Clinical Cases 2023年第32期11卷 7872-7875页

作者： Yan-Qiu Xu Miao Wang Ying Zhang Department of Rheumatology Chongqing Hospital of Traditional Chinese MedicineChongqing 400021China

BACKGROUND Pediatric-onset systemic lupus erythematosus(SLE)is typically more severe than adult-onset SLE,with a higher incidence of nervous system *** is a relatively rare neurological complication reported in 2.4%-7%of SLE *** particular,chorea induced by glucocorticoid dose reduction is even ***,we report the case of a girl with SLE,who developed chorea during the process of glucocorticoid therapy *** SUMMARY We describe a 14-year-old girl who was diagnosed with *** was treated with methylprednisolone and rituximab,and her symptoms *** the second day after the methylprednisolone dose was reduced according to the treatment guidelines,the patient developed *** condition improved after adjusting her glucocorticoid *** This case is a reminder that extra attention to chorea is required in SLE patients during glucocorticoid dose reduction.

关键词： glucocorticoid Chorea Pediatric systemic lupus erythematosus Case report

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Clinical evidence of an interferon-glucocorticoid therapeutic synergy in COVID-19

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Signal Transduction and Targeted Therapy 2021年第4期6卷 1254-1264页

作者： Yingying Lu Feng Liu Gangling Tong Feng Qiu Pinhong Song Xiaolin Wang Xiafei Zou Deyun Wan Miao Cui Yunsheng Xu Zhihua Zheng Peng Hong Department of Biomedical Science Shenzhen Research InstituteCity University of Hong KongKowloon TongHong KongChina Department of Nephrology Center of Nephrology and UrologySun Yat-sen University Seventh HospitalShenzhenGuangdongChina Department of Infectious Diseases Suizhou Zengdu HospitalSuizhouHubeiChina Department of Oncology Peking University Shenzhen HospitalShenzhenGuangdongChina Intensive Care Unit Suizhou Zengdu HospitalSuizhouHubeiChina Department of Respiratory Medicine Suizhou Zengdu HospitalSuizhouHubeiChina Department of Pathology Mount Sinai St.Luke's Roosevelt Hospital CenterNew YorkNYUSA Department of Dermatology Sun Yat-sen University Seventh HospitalShenzhenGuangdongChina Division of Research and Development US Department of Veterans Affairs New York Harbor Healthcare SystemBrooklynNYUSA Department of Cell Biology State University of New York Downstate Health Sciences UniversityBrooklynNYUSA

Synthetic glucocorticoid dexamethasone is the first trial-proven drug that reduces COVID-19 mortality by suppressing immune *** contrast,interferons are a crucial component of host antiviral immunity and can be directly suppressed by *** investigate whether therapeutic interferons can compensate glucocorticoids-induced loss of antiviral immunity,we retrospectively analyzed a cohort of 387 PCR-confirmed COVID-19 patients with quasi-random exposure to interferons and conditional exposure to *** patients receiving glucocorticoids,early interferon therapy was associated with earlier hospital discharge(adjusted HR 1.68,95%Cl 1.19-2.37)and symptom relief(adjusted HR 1.48;95%Cl 1.06-2.08),while these associations were insignificant among glucocorticoids *** interferon therapy was also associated with lower prevalence of prolonged viral shedding(adjusted OR 0.24,95%Cl 0.10-0.57)only among glucocorticoids ***,these associations were glucocorticoid cumulative dose-and *** findings reveal potential therapeutic synergy between interferons and glucocorticoids in COVID-19 that warrants further investigation.

关键词： glucocorticoid therapeutic immunity

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Efficacy of the herbal pair, Radix Achyranthis Bidentatae and Eucommiae Cortex, in preventing glucocorticoid-induced osteoporosis in the zebrafish model

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Journal of Integrative Medicine 2022年第1期20卷 83-90页

作者： Joon-ho Lee Yuan-ji Wei Zhong-yan Zhou Yu-ming Hou Cheng-long Wang Li-bo Wang Hong-jin Wu Yu Zhang Wei-wei Dai Central Laboratory of Science and Technology Department Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Cardiovascular Department Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China

Objective: In traditional Chinese medicine, the herbal pair, Radix Achyranthis Bidentatae(RAB) and Eucommiae Cortex(EC), is widely used to treat osteoporosis. Herein, we determined whether this herbal pair can be used to ameliorate glucocorticoid(GC)-induced osteoporosis(GIOP) and find its optimal dosage in ***: The characteristics of the aqueous extract of RAB and EC were separately characterized using high-performance liquid chromatography. Osteoporosis was induced in 5-day post-fertilization zebrafish larvae by exposing them to 10 lmol/L dexamethasone(Dex) for 96 h. Seven combinations of different ratios of RAB and EC were co-administered. Treatment efficacy was determined by calculating zebrafish vertebral area and sum brightness, via alizarin red staining, and by detecting alkaline phosphatase(ALP)activity. Multiple regression analysis was conducted to test the optimal dosage ***: According to the Chinese Pharmacopoeia(2015), b-ecdysone(b-Ecd) is a major bioactive marker in RAB extract, while pinoresinol diglucoside(PDG) is the major marker in EC extract. Both of b-Ecd and PDG content values aligned with the Chinese Pharmacopoeia standards. Treatment with 10 lmol/L Dex reduced zebrafish vertebral area, sum brightness, and ALP activity, but RAB and EC attenuated these effects. Combining 50 mg/m L RAB and 50 mg/m L EC was optimal for preventing GIOP in *** transcription-quantitative polymerase chain reaction was used to evaluate the m RNA expression of osteogenesis-related genes. A treatment of 10 lmol/L Dex decreased runt-related transcription factor 2(Runx2), osteogenic protein-1(OP-1), bone c-carboxyglutamic acid-containing protein(BGLAP), and bcatenin levels. This effect was counteracted by RAB and EC co-treatment(P < 0.05). Additionally, the effect of using the two herbal extracts together was better than single-herb treatments separately. These results demonstrated that RAB and EC preserve osteoblast function in the pre

关键词： glucocorticoid Osteoporosis Radix Achyranthis Bidentatae Eucommiae Cortex Zebrafish

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