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

The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental challenges.In 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 neuroplasticity.The 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 mechanisms.Protein 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 functions.An 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 impairment.Patients 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 expression.This review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive activities.It emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive impairment.This provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.

Shenqi Fuzheng injection alleviates chemotherapy-induced cachexia by restoring glucocorticoid signaling in hypothalamus

Chemotherapy-induced cachexia(CIC)is a debilitating condition characterized by weight loss,muscle atrophy,and anorexia[1].While peripheral mechanisms of cachexia have been extensively studied,the involvement of the central nervous system(CNS)in CIC is often overlooked.Chemotherapeutic drugs cause stress responses and inflammation,which may impact the hypothalamus and disrupt systemic energy and neuroendocrine functions.Understanding hypothalamic roles in regulating these processes can provide insights into CIC's mechanisms and aid in developing novel therapies.

Comparison of inebilizumab or rituximab in addition to glucocorticoid therapy for neuromyelitis optica spectrum disorders

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.

Glucocorticoids-based prodrug design:Current strategies and research progress

Attributing to their broad pharmacological effects encompassing anti-inflammation,antitoxin,and immunosuppression,glucocorticoids(GCs)are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus,nephritis,arthritis,ulcerative colitis,asthma,keratitis,macular edema,and leukemia.However,longterm use often causes undesirable side effects,including metabolic disorders-induced Cushing's syndrome(buffalo back,full moon face,hyperglycemia,etc.),osteoporosis,aggravated infection,psychosis,glaucoma,and cataract.These notorious side effects seriously compromise patients'quality of life,especially in patients with chronic diseases.Therefore,glucocorticoid-based advanced drug delivery systems for reducing adverse effects have received extensive attention.Among them,prodrugs have the advantages of low investment,low risk,and high success rate,making them a promising strategy.In this review,we propose the strategies for the design and summarize current research progress of glucocorticoid-based prodrugs in recent decades,including polymer-based prodrugs,dendrimer-based prodrugs,antibody-drug conjugates,peptide-drug conjugates,carbohydrate-based prodrugs,aliphatic acid-based prodrugs and so on.Besides,we also raise issues that need to be focused on during the development of glucocorticoid-based prodrugs.This review is expected to be helpful for the research and development of novel GCs and prodrugs.

Study of the Effects of Glucocorticoid on Growth and Adult Final Height in Children with Primary Nephrotic Syndrome

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.

Combination treatment with telitacicept,mycophenolate mofetil and glucocorticoids for immunoglobulin A nephropathy:A case report

BACKGROUND Telitacicept reduces B cell activation and abnormal immunoglobulin A(IgA)antibody production by inhibiting the activity of B lymphocyte stimulator(BLyS)and a proliferation-inducing ligand(APRIL),thereby decreasing IgA deposition in the glomeruli and local inflammatory response.This ultimately protects the kidneys from damage.This mechanism suggests that Telitacicept has potential efficacy in the treatment of IgA nephropathy.CASE SUMMARY We present the case of a 24-year-old female who was diagnosed with IgA nephropathy due to significant proteinuria and mild renal impairment.Pathologically,she exhibited focal proliferative glomerulonephritis.Treatment with angiotensin II receptor blocker,hormones,and mycophenolate mofetil did not lead to a significant improvement in her condition.However,upon the addition of telitacicept,the patient’s renal function recovered and her proteinuria rapidly reduced.Hormones were swiftly tapered and discontinued,with no occurrence of severe infections or related complications.CONCLUSION Telitacicept combined with hormones and mycophenolate mofetil may be a safe and effective induction therapy for IgA nephropathy.

Progress in the Use of Glucocorticoids and Biological Agents in Non-Infectious Uveitis

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.

Glucocorticoid therapy in pancreatic portal hypertension associated with autoimmune pancreatitis:A case report

BACKGROUND Autoimmune pancreatitis(AIP)is a chronic form of pancreatitis characterized by diffused enlargement of the pancreas and irregular stenosis of the main pancreatic duct.Some studies have reported that AIP can cause hemorrhage of gastric varices(GV)related to portal hypertension(PH).However,such cases are rare.In addition,the association of PH with AIP is unclear.At the same time,the efficacy and duration of glucocorticoid therapy is also controversial.CASE SUMMARY In this case,we reported a case of GV in pancreatic PH associated with AIP.Enhanced abdominal computed tomography(CT)suggested splenic vein(SV)and superior mesenteric vein(SMV)thromboses.The patient received a long-term glucocorticoid therapy,that the initial dose of 40 mg is reduced weekly by 5 mg,and then reduced to 5 mg for long-term maintenance.CT and gastroscopic examination after 8 mo of treatment indicated that SV and SMV were recanalized,pancreatic stiffness and swelling were ameliorated,and the GV almost completely disappeared.CONCLUSION Long-term glucocorticoid therapy can alleviate the development of GV in patients with AIP and has potential reversibility.

Home-Nebulized Inhaled Glucocorticoid Therapy in Pediatric Respiratory Diseases

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.

Role of Peripheral Regulatory T Lymphocytes in Patients with Thyroid Associated Ophthalmopathy During Systemic Glucocorticoid Treatment:A Prospective Observational Study

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.

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

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.

Association analysis of BclI with benign lymphoepithelial lesions of the lacrimal gland and glucocorticoids resistance

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.

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

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.

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

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.

Effect of Gubi Tongxiao granules on osteoblast injury induced by glucocorticoid

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.

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

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.

Efficacy and anti-inflammatory analysis of glucocorticoid,antihistamine and leukotriene receptor antagonist in the treatment of allergic rhinitis

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.

Transcription factor glucocorticoid modulatory element-binding protein 1 promotes hepatocellular carcinoma progression by activating Yes-associate protein 1

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.

Occurrences of Glucocorticoids in Aquatic Environment and Their Removal during Wastewater Treatment

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.

Advances in glucocorticoid-mediated stroke-associated immunosuppression

Acute ischemic stroke is often accompanied by complications such as infection.After acute isch-emic stroke,immunosuppression can occur as a mechanism to prevent an excessive inflammatory response. Glucocorticoid,an important product of the hypothalamic-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.