AIM:To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders(NMOSD).METHODS:A total of 33 patients with NMOSD treated with inebilizumab(Group INB,n=15)or rituximab(...AIM:To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders(NMOSD).METHODS:A total of 33 patients with NMOSD treated with inebilizumab(Group INB,n=15)or rituximab(Group RTX,n=18)in addition to high-dose glucocorticoids were included.Both groups underwent hormone shock therapy during the acute phase.Subsequently,Group INB received inebilizumab injections during the remission phase,while Group RTX received rituximab injections.A comparison of aquaporins 4(AQP4)titer values,peripheral blood B lymphocyte counts,and visual function recovery was conducted before and 8wk after treatment.Additionally,adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes.RESULTS:Following inebilizumab treatment,there was a significantly improvement in the visual acuity of NMOSD patients(P<0.05),accompanied by a notable decrease in AQP4 titer values and B lymphocyte ratio(P<0.05).Moreover,inebilizumab treatment showed a partial effect in preventing optic nerve atrophy(P<0.05).However,there were no significant differences in other therapeutic effects compared to rituximab,which has previously demonstrated substantial therapeutic efficacy(P>0.05).Furthermore,inebilizumab exhibited higher safety levels than that of rituximab injections.CONCLUSION:The combination of inebilizumab and high-dose glucocorticoids proves to be effective.In comparison to rituximab injections,inebilizumab displays better tolerance and safety.Moreover,it demonstrates a partial effect in preventing optic nerve atrophy.Thus,it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD.展开更多
Objective: To analyze the epidemiological characteristics of growth, as well as factors associated with growth retardation in children with primary nephrotic syndrome (PNS), and to investigate the effect of glucocorti...Objective: To analyze the epidemiological characteristics of growth, as well as factors associated with growth retardation in children with primary nephrotic syndrome (PNS), and to investigate the effect of glucocorticoid (GC) use duration on growth retardation in these children. Methods: Clinical and laboratory data of 353 PNS children treated at our hospital from July 2014 to June 2015 were collected through the medical record management system. Height, weight, and GC usage were recorded. Follow-up assessments were conducted in August 2022 for the original group, recording height, weight, and GC usage. Height and weight were evaluated using standard deviation scores (SDS). Categorical data were analyzed using chi-square test while continuous measurement data were analyzed using t-test or rank-sum test. Linear regression was used to assess the association between two single independent variables, and logistic regression analysis was used to screen for risk factors related to growth retardation in children with PNS. Results: Among the 353 PNS children enrolled in this study, male-to-female ratio of 2.64:1 (256 males vs 97 females). A total of 119 children exhibited growth retardation, incidence rate of 33.71%. The duration of GC usage among those with growth retardation was significantly longer compared to those without it (762.81 ± 934.50 days vs 263.77 ± 420.49 days;p Conclusion: PNS children treated with GC have a high incidence of growth retardation, and a high proportion of short stature in adulthood, especially in children with growth retardation in childhood, most of them have short stature after grown up. Time of GC usage is a risk factor for growth retardation in children with PNS.展开更多
One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing prom...One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing promise in the management of this condition. The description of glucocorticoid and biologic usage in non-infectious uveitis is the main topic of this paper.展开更多
Objective:To evaluate the therapeutic effect of home-nebulized inhaled glucocorticoid therapy in pediatric respiratory diseases.Methods:60 cases of children with respiratory diseases admitted between October 2022 and ...Objective:To evaluate the therapeutic effect of home-nebulized inhaled glucocorticoid therapy in pediatric respiratory diseases.Methods:60 cases of children with respiratory diseases admitted between October 2022 and October 2023 were selected as study subjects and randomly divided into the control group and the observation group,30 cases each.The control group was provided with conventional treatment only,while the observation group was provided with home-nebulized inhalation glucocorticosteroid treatment,and the treatment effects,clinical symptom relief time,disease recurrence rate,and treatment satisfaction of the children’s families were recorded and compared between the two groups.Results:A comparison of the two groups in terms of gender and age showed that the differences were not statistically significant(P>0.05).In terms of clinical efficacy,the total effective rate of the observation group was 90.00%,which was significantly higher than that of the control group of 66.67%(P<0.05).Compared with the control group,the disappearance time of the clinical symptoms of the observed group was significantly shortened(P<0.05).In addition,the satisfaction scores of the families of the children in the observation group were significantly higher than those of the control group(P<0.05).Conclusion:Home-nebulized inhalation glucocorticoid therapy shows significant clinical efficacy in pediatric respiratory diseases,significantly reduces the time of disappearance of clinical symptoms,and improves the satisfaction of patients’families,which provides an effective treatment option for children.展开更多
Objective Thyroid-associated ophthalmopathy(TAO)is an autoimmune disorder involving the orbital tissue.This study aimed to understand the role of regulatory T cells(Tregs)in TAO during 12-week systemic glucocorticoid(...Objective Thyroid-associated ophthalmopathy(TAO)is an autoimmune disorder involving the orbital tissue.This study aimed to understand the role of regulatory T cells(Tregs)in TAO during 12-week systemic glucocorticoid(GC)treatment.Methods Thirty-two moderate-severe TAO patients with a clinical activity score(CAS)≥3/7 or with prolonged T2 relaxation time(T2RT)on at least one side of extraocular muscle(EOM)were enrolled.The percentage of the peripheral CD4+CD25(high)CD127(−/low)Tregs was analyzed using flow cytometry before and after the GC treatment.The activity and severity of TAO,T2RT,and the clinical outcomes after the GC treatment were assessed.Their correlation with the peripheral Tregs was investigated.Results There was no significant association between the baseline Treg fraction and the activity and severity of TAO or the treatment response.A significant reduction of Tregs was observed after the GC therapy merely in patients without any clinical improvement.Conclusion Treg reduction after systemic GC therapy is indicative of a poor therapeutic response.Accordingly,dynamic alterations of Tregs could help to evaluate the effectiveness of the GC treatment.展开更多
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 g...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 elucidated.The primary aim of the present study was to probe into the GC-induced resistance of EGFR-targeted drug afatinib and the underlying mechanism.HNSCC 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)expression.The promoting tumor growth effect of GC was evaluated by the CCK-8 assay and flow cytometry.Levels of signaling pathways participants GR,mTOR,and EGFR were determined by quantitative polymerase chain reaction and western blotting.GC increased the proliferation of HNSCC cells in a GR-dependent manner and promoted AKT/mTOR signaling.But GC failed in counteracting the inhibition of rapamycin in the mTOR signaling pathway.Besides,GC also induced resistance to EGFR-targeted drug afatinib through AKT/mTOR instead of the EGFR/ERK signaling pathway.Thus,GCs reduce the efficacy of afatinib on HNSCC,implicating a cautious use of glucocorticoids in clinical practice.展开更多
AIM:To evaluate the relationship between gene polymorphism(BclI,ER22/23EK,N363S)and the occurrence,progression and sensitivity to glucocorticoid of lacrimal gland benign lymphoepithelial lesion(LGBLEL).METHODS:Clinica...AIM:To evaluate the relationship between gene polymorphism(BclI,ER22/23EK,N363S)and the occurrence,progression and sensitivity to glucocorticoid of lacrimal gland benign lymphoepithelial lesion(LGBLEL).METHODS:Clinical peripheral blood samples of 52 LGBLEL patients and 10 normal volunteers were collected for DNA extraction and polymerase chain reaction sequencing to analyze single nucleotide polymorphism(SNP)genotypes.The lacrimal tissues of LGBLEL were surgically removed and made into paraffin sections for subsequent hematoxylin-eosin(HE)and Masson staining analysis.The duration of disease and hormone use of LGBLEL patients from diagnosis to surgery were also analyzed.The Meta-analysis follows PRISMA guidelines to conducted a systematic review of human studies investigating the relationship between the NR3C1 BclI polymorphism and glucocorticoids(GCs)sensitivity.RESULTS:There was no association between ER22/23EK or N363S and the occurrence of LGBLEL or GCs sensitivity(P>0.05);BclI GC genotype was closely related to GCs resistance(P=0.03)as is the minor allele C(P=0.0017).The HE staining and Masson staining showed that the GC genotype of BclI remarkably slowed down the disease progression and reduced fibrosis(P<0.05),especially for GCs-dependent patients(P<0.0001).Meta-analysis showed that BclI was not significantly associated with GCs responsiveness.CONCLUSION:The LGBLEL patients who carry the NR3C1 BclI allele C may be more sensitive to GCs and associated with lower fibrosis and slower disease progression.The results may guide the clinical treatment strategy for the LGBLEL patients.展开更多
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...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 dysfunction.In predisposed patients,TMA can be triggered by many environmental factors.Glucocorticoids(GCs)can compromise the vascular endothelium.However,GC-associated TMA has rarely been reported,which may be due to the lack of awareness of clinicians.Given the high frequency of thrombocytopenia during GC treatment,particular attention should be given to this potentially fatal complication.CASE 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 hemolysis.Following GC treatment,his platelet counts and hemoglobin levels rapidly decreased.After admission to our hospital,the dose of methylprednisolone was increased to 60 mg/d in an attempt to enhance the suppressive effect.However,increasing the GC dose did not alleviate hemolysis,and his cytopenia worsened.Morphological evaluation of the marrow smears revealed increased cellularity with an increased percentage of erythroid progenitors without evident dysplasia.Cluster of differentiation(CD)55 and CD59 expression was significantly decreased on erythrocytes and granulocytes.In the following days,platelet transfusion was required due to severe thrombocytopenia.Observation 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 proteins.We examined blood smears and found a small number of schistocytes,dacryocytes,acanthocytes and target cells.Discontinuation of GC treatment resulted in rapidly increased platelet counts and steady increases in hemoglobin levels.The patient’s platelet counts and hemoglobin levels returned to the levels prior to GC treatment 4 weeks after GC discontinuation.CONCLUSION GCs can drive TMA episodes.When thrombocytopenia occurs during GC treatment,TMA should be considered,and GCs should be discontinued.展开更多
BACKGROUND Glucocorticoid modulatory element-binding protein 1(GMEB1),which has been identified as a transcription factor,is a protein widely expressed in various tissues.Reportedly,the dysregulation of GMEB1 is linke...BACKGROUND Glucocorticoid modulatory element-binding protein 1(GMEB1),which has been identified as a transcription factor,is a protein widely expressed in various tissues.Reportedly,the dysregulation of GMEB1 is linked to the genesis and development of multiple cancers.AIM To explore GMEB1’s biological functions in hepatocellular carcinoma(HCC)and figuring out the molecular mechanism.METHODS GMEB1 expression in HCC tissues was analyzed employing the StarBase database.Immunohistochemical staining,Western blotting and quantitative realtime PCR were conducted to examine GMEB1 and Yes-associate protein 1(YAP1)expression in HCC cells and tissues.Cell counting kit-8 assay,Transwell assay and flow cytometry were utilized to examine HCC cell proliferation,migration,invasion and apoptosis,respectively.The JASPAR database was employed for predicting the binding site of GMEB1 with YAP1 promoter.Dual-luciferase reporter gene assay and chromatin immunoprecipitation-qPCR were conducted to verify the binding relationship of GMEB1 with YAP1 promoter region.RESULTS GMEB1 was up-regulated in HCC cells and tissues,and GMEB1 expression was correlated to the tumor size and TNM stage of HCC patients.GMEB1 overexpression facilitated HCC cell multiplication,migration,and invasion,and suppressed the apoptosis,whereas GMEB1 knockdown had the opposite effects.GMEB1 bound to YAP1 promoter region and positively regulated YAP1 expression in HCC cells.CONCLUSION GMEB1 facilitates HCC malignant proliferation and metastasis by promoting the transcription of the YAP1 promoter region.展开更多
Objective:To explore the mechanism of Gubi Tongxiao granule in treating osteoblast injury induced by glucocorticoid.Methods:Mouse osteogenic precursor cell MC3T3-E1 was cultured in vitro,the control group was conventi...Objective:To explore the mechanism of Gubi Tongxiao granule in treating osteoblast injury induced by glucocorticoid.Methods:Mouse osteogenic precursor cell MC3T3-E1 was cultured in vitro,the control group was conventionally cultured,the model group was treated with dexamethasone(10^(-5) M,10^(-6) M,10^(-7) M)solution with gradient concentration to induce injury,and the experimental group was added with Gubi Tongxiao granule drug-containing serum to intervene culture on the basis of the model group.Cell viability was detected by CCK-8 method,autophagy and apoptosis were detected by MDC/PI staining,Beclin-1,Bcl-2 and Bax expression levels were detected by Western-blot,and the expression of target genes in each group was analyzed by RT-qPCR.Results:Compared with the control group,the activity of osteoblasts in the model decreased significantly.The effect of dexamethasone on autophagy and apoptosis of MC3T3-E1 cells was time-dependent and dose-dependent(P<0.05).The autophagy marker Beclin-1 increased at low doses of dexamethasone(10^(-7) or 10^(-6) M)and decreased at high doses(10^(-5) M).Compared with model group,Beclin-1 and Bax mRNA expression in experimental group decreased(P<0.01),and Bcl-2 mRNA expression was significantly up-regulated(P<0.01).In addition,the results of semi-quantitative analysis of apoptosis staining showed that autophagy and apoptosis were inhibited in different degrees(P<0.01).Conclusion:Gubi Tongxiao granule has a protective effect on osteoblast injury caused by dexamethasone,and can effectively reduce autophagy and apoptosis induced by glucocorticoid,which may be one of the mechanisms of maintaining bone mass and delaying the occurrence and development of femoral head necrosis.展开更多
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 disease.Glucocorticoids...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 disease.Glucocorticoids are the standard treatment for severe COVID-19 pneumonia requiring oxygen supply;however,the post-COVID-19 efficacy of high-dose steroid therapy remains unclear.Here,we presented a case of an 81-year-old man who developed acute respiratory failure after COVID-19 and was treated with glucocorticoid pulse therapy.CASE SUMMARY An 81-year-old man with no respiratory symptoms was admitted due to a diabetic foot.He had been previously treated for COVID-19 pneumonia six weeks prior.However,upon admission,he suddenly complained of dyspnea and required a high-flow oxygen supply.Initial simple chest radiography and computed tomography(CT)revealed diffuse ground-glass opacities and consolidation in both lungs.However,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 demand.The patient was diagnosed with post-COVID-19 organizing pneumonia.Thus,we initiated glucocorticoid pulse therapy of 500 mg for three days followed by a tapered dose on hospital day(HD)9.After three days of pulse treatment,the patient's oxygen demand decreased.The patient was subsequently discharged on HD 41,and chest radiography and CT scans have almost normalized nine months after discharge.CONCLUSION Glucocorticoid pulse therapy may be considered when the usual glucocorticoid dose is ineffective for patients with COVID-19 sequelae.展开更多
BACKGROUND There are many adverse reactions in the treatment of allergic rhinitis(AR)mainly with conventional drugs.Leukotriene receptor antagonists,glucocorticoids and nasal antihistamines can all be used as first-li...BACKGROUND There are many adverse reactions in the treatment of allergic rhinitis(AR)mainly with conventional drugs.Leukotriene receptor antagonists,glucocorticoids and nasal antihistamines can all be used as first-line drugs for AR,but the clinical effects of the three drugs are not clear.AIM To examine the impact of glucocorticoids,antihistamines,and leukotriene receptor antagonists on individuals diagnosed with AR,specifically focusing on their influence on serum inflammatory indexes.METHODS The present retrospective study focused on the clinical data of 80 patients diagnosed and treated for AR at our hospital between May 2019 and May 2021.The participants were categorized into the control group and the observation group.The control group received leukotriene receptor antagonists,while the observation group was administered glucocorticoids and antihistamines.Conducted an observation and comparison of the symptoms,physical sign scores,adverse reactions,and effects on serum inflammatory indexes in two distinct groups of patients,both before and after treatment.RESULTS Subsequent to treatment,the nasal itching score,sneeze score,runny nose score,nasal congestion score,and physical signs score exhibited notable discrepancies(P<0.05),with the observation group demonstrating superior outcomes compared to the control group(P<0.05).The interleukin(IL)-6,IL-10,tumor necrosis factor-alpha,Soluble Intercellular Adhesion Molecule-1,Leukotriene D4 after treatment were significantly different and the observation group It is better than the control group,which is statistically significant(P<0.05).Following the intervention,the incidence of adverse reactions in the observation group,including symptoms such as nasal dryness,discomfort in the throat,bitter taste in the mouth,and minor erosion of the nasal mucosa,was found to be 7.5%.This rate was significantly lower compared to the control group,which reported an incidence of 27.5%.The difference between the two groups was statistically significant(P<0.05).CONCLUSION Glucocorticoids and antihistamines have obvious therapeutic effects,reduce serum inflammatory index levels,relieve symptoms and signs of patients,and promote patients'recovery,which can provide a reference for clinical treatment of AR.展开更多
BACKGROUND Pediatric-onset systemic lupus erythematosus(SLE)is typically more severe than adult-onset SLE,with a higher incidence of nervous system involvement.Chorea is a relatively rare neurological complication rep...BACKGROUND Pediatric-onset systemic lupus erythematosus(SLE)is typically more severe than adult-onset SLE,with a higher incidence of nervous system involvement.Chorea is a relatively rare neurological complication reported in 2.4%-7%of SLE patients.In particular,chorea induced by glucocorticoid dose reduction is even rarer.Herein,we report the case of a girl with SLE,who developed chorea during the process of glucocorticoid therapy reduction.CASE SUMMARY We describe a 14-year-old girl who was diagnosed with SLE.She was treated with methylprednisolone and rituximab,and her symptoms improved.On the second day after the methylprednisolone dose was reduced according to the treatment guidelines,the patient developed chorea.Her condition improved after adjusting her glucocorticoid regimen.CONCLUSION This case is a reminder that extra attention to chorea is required in SLE patients during glucocorticoid dose reduction.展开更多
Glucocorticoids(GCs) are a group of endocrine-disrupting compounds(EDCs) frequently prescribed against various medical conditions.Recently,GCs have been shown to be effective in managing septic shock in patients infec...Glucocorticoids(GCs) are a group of endocrine-disrupting compounds(EDCs) frequently prescribed against various medical conditions.Recently,GCs have been shown to be effective in managing septic shock in patients infected with the 2019 novel coronavirus(COVID-19).Due to colossal consumption and potential risks to aquatic organisms,GCs have immensely attracted the focus of the scientific research community as a water pollutant.Therefore,the aim of this paper is to review the current knowledge on the occurrence of various GCs in the aquatic environment and their removal during wastewater treatment.A variety of GCs are ubiquitous in surface water,hospital wastewater,and sewage water worldwide.And the minimum concentration in volume is below 0.01 ng/L,and the maximum one is 10 000 ng/L,and enter the environment through hospital and urban wastewater discharging.Compared with natural GCs,higher risks to aquatic environments could be induced by synthetic GCs.The current activated sludge processes used in wastewater treatment plants(WWTPs) are not fully effective in eliminating GCs,some of which may further increase the risk of GC in the environment.In comparison with the aerobic process in WWTPs,the anaerobic and anoxic processes were found to be more efficient for GC degradation.Of the studied GCs,fluticasone propionate,clobetasol propionate,fluocinolone acetonide,and triamcinolone acetonide need more attention due to their low removal efficiencies and strong toxicity.Among the advanced treatment processes,reverse osmosis,ultraviolet irradiation,CaO_(2),and plasma could achieve significant GC activity removal while micro/ultra-filtration,chlorination,and ozonation were less efficient.展开更多
Acute ischemic stroke is often accompa-nied by complications such as infection.After acute isch-emic stroke,immunosuppression can occur as a mech-anism to prevent an excessive inflammatory response. Glucocorticoid,an ...Acute ischemic stroke is often accompa-nied by complications such as infection.After acute isch-emic stroke,immunosuppression can occur as a mech-anism to prevent an excessive inflammatory response. Glucocorticoid,an important product of the hypothalam-ic-pituitary-adrenal axis,plays a crucial role in inducing immunosuppression in the early stage of acute cerebral infarction. Glucocorticoid not only affects the secretion of inflammatory cytokines but also influences the function of immune cells,ultimately leading to an increased risk of infection.展开更多
Objective To explore the role of glucocorticoid (GC) receptor (GR) in rapamycin's reversion of GC resistance in humanGC-resistant T-acute lymphoblastic leukemia (ALL) CEM-C1 cells. Methods CEM-C1 cells were cul...Objective To explore the role of glucocorticoid (GC) receptor (GR) in rapamycin's reversion of GC resistance in humanGC-resistant T-acute lymphoblastic leukemia (ALL) CEM-C1 cells. Methods CEM-C1 cells were cultured in vitro and treated with rapamycin at different concentrations with or without 1 μmol/L dexamethasone (Dex). 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test was performed to assess cell proliferation. The cell cycle and cell apoptosis were analyzed by flow cytometry. The expression of GRα mRNA was determined by real-time quantitative RT-PCR. The expression of GR, p-70S6K, Mcl-1, and Bim proteins was detected by Western blot. Results When incubated with rapamycin at different concentrations, CEM-C1 cells showed significant growth inhibition in a time- and concentration-dependent manner. The growth inhibition was synergistically increased when CEM-C1 cells were treated with rapamycin plus 1 μmol/L Dex. CEM-C1 cells treated with rapamycin alone showed no apparent apoptosis, and were arrested at G0/G1 phase. After the treatment with Dex plus rapamycin, CEM-C1 cells demonstrated apparent apoptosis and increased the cell cycle arrested at G0/G1 phase. Rapamycin combined with Dex up-regulated GRα, phosphorylated GR(p-GR), and pro-apoptotic protein Bim-EL in CEM-C1 cells, but inhibited the expression of p-p70S6K, a downstream target protein ofmTOR (mammalian target of rapamycin). Conclusion After the treatment with rapamycin plus Dex, Dex resistant CEM-C1 cells induce growth inhibition and apoptosis. The underlying mechanism may involve inhibition of the mTOR signaling pathway and also be associated with up-regulation of GR expression and activation of GC-GR signaling pathway.展开更多
Glucocorticoids(GCs)have been widely used as immunosuppressants and antiinflammatory agents to treat a variety of autoimmune and inflammatory diseases,and they fully exert their anti-inflammatory and immune-regulating...Glucocorticoids(GCs)have been widely used as immunosuppressants and antiinflammatory agents to treat a variety of autoimmune and inflammatory diseases,and they fully exert their anti-inflammatory and immune-regulating effects in the body.The effect of GCs on white blood cells is an important part of their action.GCs can cause changes in peripheral blood white blood cell counts by regulating the proliferation,differentiation,and apoptosis of white blood cells.Although the total number of white blood cells,neutrophil counts,lymphocytes,and eosinophils increases,the counts of basic granulocytes and macrophages decreases.In addition,GCs can regulate the activation and secretion of white blood cells,inhibit the secretion of a variety of pro-inflammatory cytokines,the expression of chemokines,and promote the production of anti-inflammatory cytokines.For patients on GC therapy,the effects of GCs on leukocytes were similar to the changes in peripheral blood caused by bacterial infections.Thus,we suggest that clinicians should be more cautious in assessing the presence of infection in children with long-term use of GCs and avoid overuse of antibiotics in the presence of elevated leukocytes.GCs work through genomic and non-genomic mechanisms in the human body,which are mediated by GC receptors.In recent years,studies have not fully clarified the mechanism of GCs,and further research on these mechanisms will help to develop new therapeutic strategies.展开更多
Glucocorticoids have been used in the treatment of prostate cancer to slow disease progression, improve pain control and offset side effects of chemo- and hormonal therapy. However, they may also have the potential to...Glucocorticoids have been used in the treatment of prostate cancer to slow disease progression, improve pain control and offset side effects of chemo- and hormonal therapy. However, they may also have the potential to drive prostate cancer growth via mutated androgen receptors or glucocorticoid receptors (GRs). In this review we examine historical and contemporary use of glucocorticoids in the treatment of prostate cancer, review potential mechanisms by which they may inhibit or drive prostate cancer growth, and describe potential means of defining their contribution to the biology of prostate cancer.展开更多
OBJECTIVE To investigate the anti-rheumatoid arthritis(RA)effect of Escin combined with low dose of GCs(dexameth⁃asone,Dex)and its underlying mechanism.METHODS Adjuvant-induced rheumatoid arthritis rats and LPS-injure...OBJECTIVE To investigate the anti-rheumatoid arthritis(RA)effect of Escin combined with low dose of GCs(dexameth⁃asone,Dex)and its underlying mechanism.METHODS Adjuvant-induced rheumatoid arthritis rats and LPS-injured RAW 264.7 were used to investigate the anti-RA effects of Escin combined with low dose Dex in vivo and in vitro.In vivo experiment:rats were randomly divided into model group(AIA),dexamethasone high dose(Dex,0.2 mg·kg^-1)group,dexamethasone low dose(Dex,0.05 mg·kg^-1)group,Escin 10 mg·kg^-1 group,Dex 0.05+Escin group,10 rats in each group,another 10 were used as normal control group.The vehicle and the corresponding drug were administered intragastrically(ig)daily for 14 d.In vitro experiment:LPS was used to stimulate RAW 264.7 macrophages for inflammatory models,which were divided into control group,LPS group,Dex with high dose(50 nmol·L^-1)group,and Dex with low dose(12.5 nmol·L^-1)group.In the Escin 10μmol·L^-1 group and the Dex+Escin(12.5 nmol·L^-1+10μmol·L^-1)group,the corresponding drugs were added to each well.After 2 h,LPS was added to induce inflammation.RESULTS Escin combined with low dose Dex significantly decreased arthritic index,serum IL-6 and TNF-α,improved paw swelling,and ameliorated the joint pathology immune organ pathology significantly.Gene chip results revealed that Nr3c1(GR)altered significantly.And that GR activation by Escin and low dose Dex was confirmed both in vivo and in vitro.Furthermore,Escin combined with low dose Dex also significant increase GR mRNA expression.However,when suppression of GR by its specific inhibitor,the anti-RA effect of Escin combined with low dose Dex was abolished.CONCLUSION Escin combined with Dex reduces the dose of Dex,and exerts significant anti-RA effects,which could also reduce the adverse effects of Dex.This combination might be attributed to GR activation.This study might provide a new combination drugs for the treatment of RA.展开更多
The effect of dexamethasone with different concentrations and different stimulating periods on the expression of glucocorticoid receptors (GRα, GRβ) protein was investigated in human monocyte cell line THP-1. The ...The effect of dexamethasone with different concentrations and different stimulating periods on the expression of glucocorticoid receptors (GRα, GRβ) protein was investigated in human monocyte cell line THP-1. The cultured human monocyte line THP-1 cells were stimulated by dexamethasone with different concentrations and different periods. The expression of GRα and GRβ protein was detected by Western hlotting. The results showed that the expression of GRα and GRβ was detected in the THP-1 cells, The quantity of GRα expression was reduced by dexamethasone under the same concentration with the prolongation of expression was increased by dexamethasone treatment the stimulating periods. The quantity of GRβ in a time- and dose-dependent manner. It was concluded that dexamethasone stimulation time-dependently reduced the GRα expression in THP-1 cells. Dexamethasone stimulation time- and dose-dependently increased the GRβ expression in THP- 1 cells. The expression of GRα and GRβas regulated by glucocorticoid.展开更多
文摘AIM:To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders(NMOSD).METHODS:A total of 33 patients with NMOSD treated with inebilizumab(Group INB,n=15)or rituximab(Group RTX,n=18)in addition to high-dose glucocorticoids were included.Both groups underwent hormone shock therapy during the acute phase.Subsequently,Group INB received inebilizumab injections during the remission phase,while Group RTX received rituximab injections.A comparison of aquaporins 4(AQP4)titer values,peripheral blood B lymphocyte counts,and visual function recovery was conducted before and 8wk after treatment.Additionally,adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes.RESULTS:Following inebilizumab treatment,there was a significantly improvement in the visual acuity of NMOSD patients(P<0.05),accompanied by a notable decrease in AQP4 titer values and B lymphocyte ratio(P<0.05).Moreover,inebilizumab treatment showed a partial effect in preventing optic nerve atrophy(P<0.05).However,there were no significant differences in other therapeutic effects compared to rituximab,which has previously demonstrated substantial therapeutic efficacy(P>0.05).Furthermore,inebilizumab exhibited higher safety levels than that of rituximab injections.CONCLUSION:The combination of inebilizumab and high-dose glucocorticoids proves to be effective.In comparison to rituximab injections,inebilizumab displays better tolerance and safety.Moreover,it demonstrates a partial effect in preventing optic nerve atrophy.Thus,it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD.
文摘Objective: To analyze the epidemiological characteristics of growth, as well as factors associated with growth retardation in children with primary nephrotic syndrome (PNS), and to investigate the effect of glucocorticoid (GC) use duration on growth retardation in these children. Methods: Clinical and laboratory data of 353 PNS children treated at our hospital from July 2014 to June 2015 were collected through the medical record management system. Height, weight, and GC usage were recorded. Follow-up assessments were conducted in August 2022 for the original group, recording height, weight, and GC usage. Height and weight were evaluated using standard deviation scores (SDS). Categorical data were analyzed using chi-square test while continuous measurement data were analyzed using t-test or rank-sum test. Linear regression was used to assess the association between two single independent variables, and logistic regression analysis was used to screen for risk factors related to growth retardation in children with PNS. Results: Among the 353 PNS children enrolled in this study, male-to-female ratio of 2.64:1 (256 males vs 97 females). A total of 119 children exhibited growth retardation, incidence rate of 33.71%. The duration of GC usage among those with growth retardation was significantly longer compared to those without it (762.81 ± 934.50 days vs 263.77 ± 420.49 days;p Conclusion: PNS children treated with GC have a high incidence of growth retardation, and a high proportion of short stature in adulthood, especially in children with growth retardation in childhood, most of them have short stature after grown up. Time of GC usage is a risk factor for growth retardation in children with PNS.
文摘One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing promise in the management of this condition. The description of glucocorticoid and biologic usage in non-infectious uveitis is the main topic of this paper.
文摘Objective:To evaluate the therapeutic effect of home-nebulized inhaled glucocorticoid therapy in pediatric respiratory diseases.Methods:60 cases of children with respiratory diseases admitted between October 2022 and October 2023 were selected as study subjects and randomly divided into the control group and the observation group,30 cases each.The control group was provided with conventional treatment only,while the observation group was provided with home-nebulized inhalation glucocorticosteroid treatment,and the treatment effects,clinical symptom relief time,disease recurrence rate,and treatment satisfaction of the children’s families were recorded and compared between the two groups.Results:A comparison of the two groups in terms of gender and age showed that the differences were not statistically significant(P>0.05).In terms of clinical efficacy,the total effective rate of the observation group was 90.00%,which was significantly higher than that of the control group of 66.67%(P<0.05).Compared with the control group,the disappearance time of the clinical symptoms of the observed group was significantly shortened(P<0.05).In addition,the satisfaction scores of the families of the children in the observation group were significantly higher than those of the control group(P<0.05).Conclusion:Home-nebulized inhalation glucocorticoid therapy shows significant clinical efficacy in pediatric respiratory diseases,significantly reduces the time of disappearance of clinical symptoms,and improves the satisfaction of patients’families,which provides an effective treatment option for children.
基金supported by the National Natural Science Foundation of China(No.81100581)the Beijing Bethune Charitable Foundation(No.2021).
文摘Objective Thyroid-associated ophthalmopathy(TAO)is an autoimmune disorder involving the orbital tissue.This study aimed to understand the role of regulatory T cells(Tregs)in TAO during 12-week systemic glucocorticoid(GC)treatment.Methods Thirty-two moderate-severe TAO patients with a clinical activity score(CAS)≥3/7 or with prolonged T2 relaxation time(T2RT)on at least one side of extraocular muscle(EOM)were enrolled.The percentage of the peripheral CD4+CD25(high)CD127(−/low)Tregs was analyzed using flow cytometry before and after the GC treatment.The activity and severity of TAO,T2RT,and the clinical outcomes after the GC treatment were assessed.Their correlation with the peripheral Tregs was investigated.Results There was no significant association between the baseline Treg fraction and the activity and severity of TAO or the treatment response.A significant reduction of Tregs was observed after the GC therapy merely in patients without any clinical improvement.Conclusion Treg reduction after systemic GC therapy is indicative of a poor therapeutic response.Accordingly,dynamic alterations of Tregs could help to evaluate the effectiveness of the GC treatment.
基金supported by the Research Funding(No.RCDWJS 2020-20)Research and Development Program(RD-02-202002)from West China School/Hospital of Stomatology Sichuan University+1 种基金the Natural Science Foundation of China(81902784&81872207)Sichuan Provincial Fund of China(2022YFSY0058).
文摘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 elucidated.The primary aim of the present study was to probe into the GC-induced resistance of EGFR-targeted drug afatinib and the underlying mechanism.HNSCC 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)expression.The promoting tumor growth effect of GC was evaluated by the CCK-8 assay and flow cytometry.Levels of signaling pathways participants GR,mTOR,and EGFR were determined by quantitative polymerase chain reaction and western blotting.GC increased the proliferation of HNSCC cells in a GR-dependent manner and promoted AKT/mTOR signaling.But GC failed in counteracting the inhibition of rapamycin in the mTOR signaling pathway.Besides,GC also induced resistance to EGFR-targeted drug afatinib through AKT/mTOR instead of the EGFR/ERK signaling pathway.Thus,GCs reduce the efficacy of afatinib on HNSCC,implicating a cautious use of glucocorticoids in clinical practice.
基金Supported by Natural Science Foundation of Beijing(No.7222025)Beijing Hospitals Authority’Ascent Plan(No.DFL20190201)Natural Science Foundation of Beijing Projects(No.81602408).
文摘AIM:To evaluate the relationship between gene polymorphism(BclI,ER22/23EK,N363S)and the occurrence,progression and sensitivity to glucocorticoid of lacrimal gland benign lymphoepithelial lesion(LGBLEL).METHODS:Clinical peripheral blood samples of 52 LGBLEL patients and 10 normal volunteers were collected for DNA extraction and polymerase chain reaction sequencing to analyze single nucleotide polymorphism(SNP)genotypes.The lacrimal tissues of LGBLEL were surgically removed and made into paraffin sections for subsequent hematoxylin-eosin(HE)and Masson staining analysis.The duration of disease and hormone use of LGBLEL patients from diagnosis to surgery were also analyzed.The Meta-analysis follows PRISMA guidelines to conducted a systematic review of human studies investigating the relationship between the NR3C1 BclI polymorphism and glucocorticoids(GCs)sensitivity.RESULTS:There was no association between ER22/23EK or N363S and the occurrence of LGBLEL or GCs sensitivity(P>0.05);BclI GC genotype was closely related to GCs resistance(P=0.03)as is the minor allele C(P=0.0017).The HE staining and Masson staining showed that the GC genotype of BclI remarkably slowed down the disease progression and reduced fibrosis(P<0.05),especially for GCs-dependent patients(P<0.0001).Meta-analysis showed that BclI was not significantly associated with GCs responsiveness.CONCLUSION:The LGBLEL patients who carry the NR3C1 BclI allele C may be more sensitive to GCs and associated with lower fibrosis and slower disease progression.The results may guide the clinical treatment strategy for the LGBLEL patients.
基金Supported by Specialized Scientific Research Fund Projects of The Medical Group of Qingdao University,No.YLJT20201002.
文摘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 dysfunction.In predisposed patients,TMA can be triggered by many environmental factors.Glucocorticoids(GCs)can compromise the vascular endothelium.However,GC-associated TMA has rarely been reported,which may be due to the lack of awareness of clinicians.Given the high frequency of thrombocytopenia during GC treatment,particular attention should be given to this potentially fatal complication.CASE 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 hemolysis.Following GC treatment,his platelet counts and hemoglobin levels rapidly decreased.After admission to our hospital,the dose of methylprednisolone was increased to 60 mg/d in an attempt to enhance the suppressive effect.However,increasing the GC dose did not alleviate hemolysis,and his cytopenia worsened.Morphological evaluation of the marrow smears revealed increased cellularity with an increased percentage of erythroid progenitors without evident dysplasia.Cluster of differentiation(CD)55 and CD59 expression was significantly decreased on erythrocytes and granulocytes.In the following days,platelet transfusion was required due to severe thrombocytopenia.Observation 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 proteins.We examined blood smears and found a small number of schistocytes,dacryocytes,acanthocytes and target cells.Discontinuation of GC treatment resulted in rapidly increased platelet counts and steady increases in hemoglobin levels.The patient’s platelet counts and hemoglobin levels returned to the levels prior to GC treatment 4 weeks after GC discontinuation.CONCLUSION GCs can drive TMA episodes.When thrombocytopenia occurs during GC treatment,TMA should be considered,and GCs should be discontinued.
文摘BACKGROUND Glucocorticoid modulatory element-binding protein 1(GMEB1),which has been identified as a transcription factor,is a protein widely expressed in various tissues.Reportedly,the dysregulation of GMEB1 is linked to the genesis and development of multiple cancers.AIM To explore GMEB1’s biological functions in hepatocellular carcinoma(HCC)and figuring out the molecular mechanism.METHODS GMEB1 expression in HCC tissues was analyzed employing the StarBase database.Immunohistochemical staining,Western blotting and quantitative realtime PCR were conducted to examine GMEB1 and Yes-associate protein 1(YAP1)expression in HCC cells and tissues.Cell counting kit-8 assay,Transwell assay and flow cytometry were utilized to examine HCC cell proliferation,migration,invasion and apoptosis,respectively.The JASPAR database was employed for predicting the binding site of GMEB1 with YAP1 promoter.Dual-luciferase reporter gene assay and chromatin immunoprecipitation-qPCR were conducted to verify the binding relationship of GMEB1 with YAP1 promoter region.RESULTS GMEB1 was up-regulated in HCC cells and tissues,and GMEB1 expression was correlated to the tumor size and TNM stage of HCC patients.GMEB1 overexpression facilitated HCC cell multiplication,migration,and invasion,and suppressed the apoptosis,whereas GMEB1 knockdown had the opposite effects.GMEB1 bound to YAP1 promoter region and positively regulated YAP1 expression in HCC cells.CONCLUSION GMEB1 facilitates HCC malignant proliferation and metastasis by promoting the transcription of the YAP1 promoter region.
基金General Program of Anhui Natural Science Foundation(2008085MH281)University Natural Science Research Project of Anhui Provincial Department of Education(KJ2020A0403)。
文摘Objective:To explore the mechanism of Gubi Tongxiao granule in treating osteoblast injury induced by glucocorticoid.Methods:Mouse osteogenic precursor cell MC3T3-E1 was cultured in vitro,the control group was conventionally cultured,the model group was treated with dexamethasone(10^(-5) M,10^(-6) M,10^(-7) M)solution with gradient concentration to induce injury,and the experimental group was added with Gubi Tongxiao granule drug-containing serum to intervene culture on the basis of the model group.Cell viability was detected by CCK-8 method,autophagy and apoptosis were detected by MDC/PI staining,Beclin-1,Bcl-2 and Bax expression levels were detected by Western-blot,and the expression of target genes in each group was analyzed by RT-qPCR.Results:Compared with the control group,the activity of osteoblasts in the model decreased significantly.The effect of dexamethasone on autophagy and apoptosis of MC3T3-E1 cells was time-dependent and dose-dependent(P<0.05).The autophagy marker Beclin-1 increased at low doses of dexamethasone(10^(-7) or 10^(-6) M)and decreased at high doses(10^(-5) M).Compared with model group,Beclin-1 and Bax mRNA expression in experimental group decreased(P<0.01),and Bcl-2 mRNA expression was significantly up-regulated(P<0.01).In addition,the results of semi-quantitative analysis of apoptosis staining showed that autophagy and apoptosis were inhibited in different degrees(P<0.01).Conclusion:Gubi Tongxiao granule has a protective effect on osteoblast injury caused by dexamethasone,and can effectively reduce autophagy and apoptosis induced by glucocorticoid,which may be one of the mechanisms of maintaining bone mass and delaying the occurrence and development of femoral head necrosis.
文摘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 disease.Glucocorticoids are the standard treatment for severe COVID-19 pneumonia requiring oxygen supply;however,the post-COVID-19 efficacy of high-dose steroid therapy remains unclear.Here,we presented a case of an 81-year-old man who developed acute respiratory failure after COVID-19 and was treated with glucocorticoid pulse therapy.CASE SUMMARY An 81-year-old man with no respiratory symptoms was admitted due to a diabetic foot.He had been previously treated for COVID-19 pneumonia six weeks prior.However,upon admission,he suddenly complained of dyspnea and required a high-flow oxygen supply.Initial simple chest radiography and computed tomography(CT)revealed diffuse ground-glass opacities and consolidation in both lungs.However,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 demand.The patient was diagnosed with post-COVID-19 organizing pneumonia.Thus,we initiated glucocorticoid pulse therapy of 500 mg for three days followed by a tapered dose on hospital day(HD)9.After three days of pulse treatment,the patient's oxygen demand decreased.The patient was subsequently discharged on HD 41,and chest radiography and CT scans have almost normalized nine months after discharge.CONCLUSION Glucocorticoid pulse therapy may be considered when the usual glucocorticoid dose is ineffective for patients with COVID-19 sequelae.
文摘BACKGROUND There are many adverse reactions in the treatment of allergic rhinitis(AR)mainly with conventional drugs.Leukotriene receptor antagonists,glucocorticoids and nasal antihistamines can all be used as first-line drugs for AR,but the clinical effects of the three drugs are not clear.AIM To examine the impact of glucocorticoids,antihistamines,and leukotriene receptor antagonists on individuals diagnosed with AR,specifically focusing on their influence on serum inflammatory indexes.METHODS The present retrospective study focused on the clinical data of 80 patients diagnosed and treated for AR at our hospital between May 2019 and May 2021.The participants were categorized into the control group and the observation group.The control group received leukotriene receptor antagonists,while the observation group was administered glucocorticoids and antihistamines.Conducted an observation and comparison of the symptoms,physical sign scores,adverse reactions,and effects on serum inflammatory indexes in two distinct groups of patients,both before and after treatment.RESULTS Subsequent to treatment,the nasal itching score,sneeze score,runny nose score,nasal congestion score,and physical signs score exhibited notable discrepancies(P<0.05),with the observation group demonstrating superior outcomes compared to the control group(P<0.05).The interleukin(IL)-6,IL-10,tumor necrosis factor-alpha,Soluble Intercellular Adhesion Molecule-1,Leukotriene D4 after treatment were significantly different and the observation group It is better than the control group,which is statistically significant(P<0.05).Following the intervention,the incidence of adverse reactions in the observation group,including symptoms such as nasal dryness,discomfort in the throat,bitter taste in the mouth,and minor erosion of the nasal mucosa,was found to be 7.5%.This rate was significantly lower compared to the control group,which reported an incidence of 27.5%.The difference between the two groups was statistically significant(P<0.05).CONCLUSION Glucocorticoids and antihistamines have obvious therapeutic effects,reduce serum inflammatory index levels,relieve symptoms and signs of patients,and promote patients'recovery,which can provide a reference for clinical treatment of AR.
基金This study was conducted with the approval of the ethics committee of Chongqing Hospital of Traditional Chinese Medicine(approval No.2023-GAKY-KS-XYQ).The patient gave explicit informed consent to report her clinical case.
文摘BACKGROUND Pediatric-onset systemic lupus erythematosus(SLE)is typically more severe than adult-onset SLE,with a higher incidence of nervous system involvement.Chorea is a relatively rare neurological complication reported in 2.4%-7%of SLE patients.In particular,chorea induced by glucocorticoid dose reduction is even rarer.Herein,we report the case of a girl with SLE,who developed chorea during the process of glucocorticoid therapy reduction.CASE SUMMARY We describe a 14-year-old girl who was diagnosed with SLE.She was treated with methylprednisolone and rituximab,and her symptoms improved.On the second day after the methylprednisolone dose was reduced according to the treatment guidelines,the patient developed chorea.Her condition improved after adjusting her glucocorticoid regimen.CONCLUSION This case is a reminder that extra attention to chorea is required in SLE patients during glucocorticoid dose reduction.
基金National Natural Science Foundation of China (No. 52270062)Natural Science Foundation of Shanghai,China (No. 22ZR1402800)+1 种基金Shanghai Rising-Star Program,China (No. 23QC1400800)Shenzhen Science and Technology Program,China (No. JSGG20220606141402005)。
文摘Glucocorticoids(GCs) are a group of endocrine-disrupting compounds(EDCs) frequently prescribed against various medical conditions.Recently,GCs have been shown to be effective in managing septic shock in patients infected with the 2019 novel coronavirus(COVID-19).Due to colossal consumption and potential risks to aquatic organisms,GCs have immensely attracted the focus of the scientific research community as a water pollutant.Therefore,the aim of this paper is to review the current knowledge on the occurrence of various GCs in the aquatic environment and their removal during wastewater treatment.A variety of GCs are ubiquitous in surface water,hospital wastewater,and sewage water worldwide.And the minimum concentration in volume is below 0.01 ng/L,and the maximum one is 10 000 ng/L,and enter the environment through hospital and urban wastewater discharging.Compared with natural GCs,higher risks to aquatic environments could be induced by synthetic GCs.The current activated sludge processes used in wastewater treatment plants(WWTPs) are not fully effective in eliminating GCs,some of which may further increase the risk of GC in the environment.In comparison with the aerobic process in WWTPs,the anaerobic and anoxic processes were found to be more efficient for GC degradation.Of the studied GCs,fluticasone propionate,clobetasol propionate,fluocinolone acetonide,and triamcinolone acetonide need more attention due to their low removal efficiencies and strong toxicity.Among the advanced treatment processes,reverse osmosis,ultraviolet irradiation,CaO_(2),and plasma could achieve significant GC activity removal while micro/ultra-filtration,chlorination,and ozonation were less efficient.
基金supported by Xuanwu Hospital Na-tional Natural Youth Cultivation Project(grant number QNPY202315)the Beijing Natural Science Foundation(grant number 7212047)the National Natural Science Foundation of China(grant numbers 82171297,82101390).
文摘Acute ischemic stroke is often accompa-nied by complications such as infection.After acute isch-emic stroke,immunosuppression can occur as a mech-anism to prevent an excessive inflammatory response. Glucocorticoid,an important product of the hypothalam-ic-pituitary-adrenal axis,plays a crucial role in inducing immunosuppression in the early stage of acute cerebral infarction. Glucocorticoid not only affects the secretion of inflammatory cytokines but also influences the function of immune cells,ultimately leading to an increased risk of infection.
基金supported by the research funds from the University Program for Changjiang Scholars and Innovative Research Team(No.IRT0935)the National Natural Science Fund Project(No.30973237)grants from the Department of Science and Technology of Sichuan Province(No.2008JY0029-1,No.07FG002-024,and No.2010JY0004)
文摘Objective To explore the role of glucocorticoid (GC) receptor (GR) in rapamycin's reversion of GC resistance in humanGC-resistant T-acute lymphoblastic leukemia (ALL) CEM-C1 cells. Methods CEM-C1 cells were cultured in vitro and treated with rapamycin at different concentrations with or without 1 μmol/L dexamethasone (Dex). 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test was performed to assess cell proliferation. The cell cycle and cell apoptosis were analyzed by flow cytometry. The expression of GRα mRNA was determined by real-time quantitative RT-PCR. The expression of GR, p-70S6K, Mcl-1, and Bim proteins was detected by Western blot. Results When incubated with rapamycin at different concentrations, CEM-C1 cells showed significant growth inhibition in a time- and concentration-dependent manner. The growth inhibition was synergistically increased when CEM-C1 cells were treated with rapamycin plus 1 μmol/L Dex. CEM-C1 cells treated with rapamycin alone showed no apparent apoptosis, and were arrested at G0/G1 phase. After the treatment with Dex plus rapamycin, CEM-C1 cells demonstrated apparent apoptosis and increased the cell cycle arrested at G0/G1 phase. Rapamycin combined with Dex up-regulated GRα, phosphorylated GR(p-GR), and pro-apoptotic protein Bim-EL in CEM-C1 cells, but inhibited the expression of p-p70S6K, a downstream target protein ofmTOR (mammalian target of rapamycin). Conclusion After the treatment with rapamycin plus Dex, Dex resistant CEM-C1 cells induce growth inhibition and apoptosis. The underlying mechanism may involve inhibition of the mTOR signaling pathway and also be associated with up-regulation of GR expression and activation of GC-GR signaling pathway.
基金Supported by Provinces Co-construction Program of Medical Science and Technique Foundation of Henan Province,No.SB201901042Key Scientific Research Project of Colleges and Universities in Henan Province,No.21A320070.
文摘Glucocorticoids(GCs)have been widely used as immunosuppressants and antiinflammatory agents to treat a variety of autoimmune and inflammatory diseases,and they fully exert their anti-inflammatory and immune-regulating effects in the body.The effect of GCs on white blood cells is an important part of their action.GCs can cause changes in peripheral blood white blood cell counts by regulating the proliferation,differentiation,and apoptosis of white blood cells.Although the total number of white blood cells,neutrophil counts,lymphocytes,and eosinophils increases,the counts of basic granulocytes and macrophages decreases.In addition,GCs can regulate the activation and secretion of white blood cells,inhibit the secretion of a variety of pro-inflammatory cytokines,the expression of chemokines,and promote the production of anti-inflammatory cytokines.For patients on GC therapy,the effects of GCs on leukocytes were similar to the changes in peripheral blood caused by bacterial infections.Thus,we suggest that clinicians should be more cautious in assessing the presence of infection in children with long-term use of GCs and avoid overuse of antibiotics in the presence of elevated leukocytes.GCs work through genomic and non-genomic mechanisms in the human body,which are mediated by GC receptors.In recent years,studies have not fully clarified the mechanism of GCs,and further research on these mechanisms will help to develop new therapeutic strategies.
文摘Glucocorticoids have been used in the treatment of prostate cancer to slow disease progression, improve pain control and offset side effects of chemo- and hormonal therapy. However, they may also have the potential to drive prostate cancer growth via mutated androgen receptors or glucocorticoid receptors (GRs). In this review we examine historical and contemporary use of glucocorticoids in the treatment of prostate cancer, review potential mechanisms by which they may inhibit or drive prostate cancer growth, and describe potential means of defining their contribution to the biology of prostate cancer.
基金National Natural Science Foundation of China(8187303981973547)Natural Science Foundation of Shandong Province(ZR2017MH068)
文摘OBJECTIVE To investigate the anti-rheumatoid arthritis(RA)effect of Escin combined with low dose of GCs(dexameth⁃asone,Dex)and its underlying mechanism.METHODS Adjuvant-induced rheumatoid arthritis rats and LPS-injured RAW 264.7 were used to investigate the anti-RA effects of Escin combined with low dose Dex in vivo and in vitro.In vivo experiment:rats were randomly divided into model group(AIA),dexamethasone high dose(Dex,0.2 mg·kg^-1)group,dexamethasone low dose(Dex,0.05 mg·kg^-1)group,Escin 10 mg·kg^-1 group,Dex 0.05+Escin group,10 rats in each group,another 10 were used as normal control group.The vehicle and the corresponding drug were administered intragastrically(ig)daily for 14 d.In vitro experiment:LPS was used to stimulate RAW 264.7 macrophages for inflammatory models,which were divided into control group,LPS group,Dex with high dose(50 nmol·L^-1)group,and Dex with low dose(12.5 nmol·L^-1)group.In the Escin 10μmol·L^-1 group and the Dex+Escin(12.5 nmol·L^-1+10μmol·L^-1)group,the corresponding drugs were added to each well.After 2 h,LPS was added to induce inflammation.RESULTS Escin combined with low dose Dex significantly decreased arthritic index,serum IL-6 and TNF-α,improved paw swelling,and ameliorated the joint pathology immune organ pathology significantly.Gene chip results revealed that Nr3c1(GR)altered significantly.And that GR activation by Escin and low dose Dex was confirmed both in vivo and in vitro.Furthermore,Escin combined with low dose Dex also significant increase GR mRNA expression.However,when suppression of GR by its specific inhibitor,the anti-RA effect of Escin combined with low dose Dex was abolished.CONCLUSION Escin combined with Dex reduces the dose of Dex,and exerts significant anti-RA effects,which could also reduce the adverse effects of Dex.This combination might be attributed to GR activation.This study might provide a new combination drugs for the treatment of RA.
文摘The effect of dexamethasone with different concentrations and different stimulating periods on the expression of glucocorticoid receptors (GRα, GRβ) protein was investigated in human monocyte cell line THP-1. The cultured human monocyte line THP-1 cells were stimulated by dexamethasone with different concentrations and different periods. The expression of GRα and GRβ protein was detected by Western hlotting. The results showed that the expression of GRα and GRβ was detected in the THP-1 cells, The quantity of GRα expression was reduced by dexamethasone under the same concentration with the prolongation of expression was increased by dexamethasone treatment the stimulating periods. The quantity of GRβ in a time- and dose-dependent manner. It was concluded that dexamethasone stimulation time-dependently reduced the GRα expression in THP-1 cells. Dexamethasone stimulation time- and dose-dependently increased the GRβ expression in THP- 1 cells. The expression of GRα and GRβas regulated by glucocorticoid.