Rheumatoid arthritis(RA)is a chronic autoimmune disease that affects approxi-mately 0.46%of the global population.Conventional therapeutics for RA,including disease-modifying antirheumatic drugs(DMARDs),nonsteroidal a...Rheumatoid arthritis(RA)is a chronic autoimmune disease that affects approxi-mately 0.46%of the global population.Conventional therapeutics for RA,including disease-modifying antirheumatic drugs(DMARDs),nonsteroidal anti-inflammatory drugs(NSAIDs),and corticosteroids,frequently result in unintended adverse effects.Dexamethasone(DEX)is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive properties.Liposomal delivery of DEX,particu-larly when liposomes are surface-modified with targeting ligands like peptides or sialic acid,can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity.This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA.Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models,reduces joint inflammation and damage,and alleviates cartilage destruction compared to free DEX.The liposomal formulation also shows better hemocompatibility,fewer adverse effects on body weight and immune organ index,and a longer circulation time with higher bioavailability.The anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α(TNF-α)and B-cell-activating factor(BAFF),which are key players in the pathogenesis of RA.Additionally,liposomal DEX can induce the expres-sion of anti-inflammatory cytokines like interleukin-10(IL-10),which has significant anti-inflammatory and immunoregulatory properties.The findings suggest that lipo-somal DEX represents a promising candidate for effective and safe RA therapy,with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.展开更多
Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-i...Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.展开更多
Coronavirus disease 2019(COVID-19)is a contagious disease caused by severe acute respiratory syndrome coronavirus 2.It was declared a global pandemic on March 11,2020,by the World Health Organization.An excessive infl...Coronavirus disease 2019(COVID-19)is a contagious disease caused by severe acute respiratory syndrome coronavirus 2.It was declared a global pandemic on March 11,2020,by the World Health Organization.An excessive inflammatory response is a severe respiratory manifestation of COVID-19,which becomes predominant in later stages.Due to its immunosuppressive and anti-inflammatory properties,dexamethasone is the first systemic glucocorticoid to treat severe COVID-19 patients.This editorial reviews the efficacy and safety of highdose vs low-dose dexamethasone in patients with COVID-19.Findings indicate that using low-dose dexamethasone is beneficial and emphasize the need for additional research on the use of high-dose dexamethasone.While the study provides a robust evidence base,it is limited by the lack of long-term data,focus on specific outcomes and heterogeneity of the included studies.Future research should focus on the long-term effects of dexamethasone and its impact across varying disease severities and patient populations to refine treatment strategies and improve patient care.展开更多
The ongoing coronavirus disease 2019(COVID-19)pandemic has necessitated rapid advancements in therapeutic strategies,with dexamethasone emerging as a key treatment for severe cases.This editorial discusses the systema...The ongoing coronavirus disease 2019(COVID-19)pandemic has necessitated rapid advancements in therapeutic strategies,with dexamethasone emerging as a key treatment for severe cases.This editorial discusses the systematic review conducted by Sethi et al,published in the World Journal of Virology.The review critically examines the efficacy and safety of varying dosages of dexamethasone in severe COVID-19 patients,providing a comprehensive meta-analysis that underscores the current clinical recommendations favoring a low-dose regimen.Despite these findings,the review highlights the potential benefits of tailored dosages for specific patient subgroups,suggesting a need for personalized treatment approaches.This editorial expands on the implications of these findings,advocating for the integration of evolving clinical data into treatment protocols and calling for further research into patient-specific responses to therapy.It emphasizes the importance of adaptability and precision in pandemic response,urging the medical community to consider both the robustness of existing evidence and the potential for innovative approaches to enhance patient outcomes in the face of global health challenges.展开更多
Background: Intraperitoneal instillation (IPI) of local anesthesia was reported to reduce postoperative pain after laparoscopic surgeries. We aim to evaluate the effectiveness of IPI of bupivacaine + dexmedetomidine v...Background: Intraperitoneal instillation (IPI) of local anesthesia was reported to reduce postoperative pain after laparoscopic surgeries. We aim to evaluate the effectiveness of IPI of bupivacaine + dexmedetomidine versus bupivacaine + dexamethasone on postoperative pain in patients undergoing laparoscopic cholecystectomy (LC). Methods: This randomized clinical trial was carried out on one hundred patients who underwent LC under general anesthesia. Patients were randomly divided into: Group (Dexa): IPI of bupivacaine with dexamethasone and Group (Dexmed): IPI of bupivacaine with dexmedetomidine. Results: The first time to request analgesia was significantly delayed in the dexmed group (P value Conclusions: Intraperitoneal Bupivacaine + Dexmedetomidine provided longer pain-free postoperative duration lower pain score over time, and lesser analgesic consumption.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a major health concern in Thailand,with most patients diagnosed at the intermediate stage.Transarterial chemoembolization(TACE)is the standard treatment;however,postembolizat...BACKGROUND Hepatocellular carcinoma(HCC)is a major health concern in Thailand,with most patients diagnosed at the intermediate stage.Transarterial chemoembolization(TACE)is the standard treatment;however,postembolization syndrome(PES)remains a common complication.Although both dexamethasone(DEXA)and N-acetylcysteine(NAC)have shown efficacy in reducing PES,no study has directly compared their effects.AIM To compare the incidence of PES between DEXA and NAC in intermediate-stage HCC patients undergoing conventional TACE(cTACE).METHODS A randomized,double-blind,controlled trial was conducted at two tertiary hospitals in Thailand from November 2024 to April 2025.Eligible HCC patients(aged 18-70 years)were randomized(1:1)to receive either NAC(150 mg/kg/hour loading dose,followed by 50 mg/kg over 4 hours,then 6.25 mg/kg/hour for 48 hours post-cTACE)or DEXA(8 mg IV 1 hour before cTACE).cTACE was performed by blinded interventional radiologists.The primary outcome was PES occurrence within 48 hours,assessed using South West Oncology Group toxicity coding and the Common Terminology Criteria for Adverse Events.The secondary outcomes were post-cTACE liver decompensation and the dynamic changes in the albumin-bilirubin(ALBI)score.RESULTS A total of 56 intermediate-stage HCC patients were included(DEXA,n=28;NAC,n=28).Most had preserved liver function,with 92.9%classified as Child-Pugh A.The maximum tumor size was 6.2 cm,and 85.7%had multiple lesions.Additionally,39 patients(69.6%)met the beyond up-to-7 criteria.Overall,27 patients(48.2%)developed PES.After adjusting for confounding factors,the NAC group had a significantly lower incidence of PES than the DEXA group(32.1%vs 64.3%;adjusted odds ratio=0.17,95%confidence interval:0.03-0.87,P=0.033).Only two patients(3.6%)developed post-cTACE liver decompensation.Furthermore,51.8%patients experienced worsening ALBI scores within 48 hours post-procedure;however,the rate of ALBI score worsening did not significantly differ between the groups.CONCLUSION Compared with DEXA,NAC significantly reduces the incidence of PES,regardless of its impact on liver function recovery.Therefore,NAC is a preferable option for reducing PES in Barcelona Clinic Liver Cancer-B stage HCC patients with preserved liver function.展开更多
Background:Sudden sensorineural hearing loss(SSNHL),often associated with tinnitus,significantly impacts individuals'quality of life.Current treatments,such as free drugs via intravenous or intratympanic(IT)admini...Background:Sudden sensorineural hearing loss(SSNHL),often associated with tinnitus,significantly impacts individuals'quality of life.Current treatments,such as free drugs via intravenous or intratympanic(IT)administration of dexamethasone(DEX)and lidocaine,face limitations like low bioavailability and rapid drug clearance.To address these challenges,we developed a local co-delivery system combining DEX microcrystals(DEX MCs)and lidocaine-loaded poly(lactic-co-glycolic acid)(PLGA)non-spherical microparticles(LPNMs)for sustained drug release in the inner ear.Methods:DEX MCs and LPNMs were prepared using the traditional precipitation technique and double emulsion-solvent evaporation,respectively.After characterizing physicochemical properties and drug release kinetics,they were dispersed in sodium hyaluronate solution for IT injection,then in vivo pharmacokinetics and biocompatibility in guinea pigs were studied.Results:DEX MCs exhibited stable dissolution,while LPNMs provided sustained lidocaine release,reducing potential side effects.In vivo studies in guinea pigs demonstrated prolonged drug retention in the perilymph and improved pharmacokinetics.Histological evaluation confirmed the good biocompatibility of this combined delivery system,with no significant inner ear damage observed.Conclusion:This co-delivery system can be used as a depot for delivering both DEX and lidocaine to the inner ear and offers a promising approach for the synergistic treatment of SSNHL associated with tinnitus.展开更多
Glucocorticoids are widely utilized for treating various immune and inflammation-related diseases,prompting significant interest in their potential application for COVID-19 treatment.This study explored the efficacy a...Glucocorticoids are widely utilized for treating various immune and inflammation-related diseases,prompting significant interest in their potential application for COVID-19 treatment.This study explored the efficacy and safety of dexamethasone(DEX)and methylprednisolone(MP)in treating severe COVID-19.A cohort of 94 adult patients,aged 18 years and older,with severe COVID-19 was recruited.They received intravenous MP(40-80 mg/d)or DEX(5-10 mg/d)for 7-10 d.The primary objective was to assess the effects of these treatments on mortality rates.Additionally,the study aimed to compare the impact of these medications on various parameters,including the oxygenation index,inflammatory index,fungal infections,and hyperglycemia,serving as secondary endpoints.The findings revealed no fatalities in either group.However,there was one case of pulmonary fibrosis and Aspergillus fumigatus infection in the DEX group,and two cases of Aspergillus infection in the MP group.Although the differences were not statistically significant(P>0.05),the MP group showed a faster improvement in blood oxygen saturation compared to the DEX group,with a median time of 5 d vs 7 d.No statistically significant difference was observed between the two groups regarding improvement in C-reactive protein levels(P>0.05).Notably,DEX was associated with a higher incidence of hyperglycemia compared to MP(P<0.05).Both DEX and MP significantly reduced mortality rates among patients with severe COVID-19 and improved blood oxygen saturation and inflammatory markers.However,MP exhibited a more rapid onset of efficacy and fewer adverse reactions.展开更多
Dexamethasone is a common glucocorticoid medication with adverse effects that can cause muscle atrophy,but no drug intervention has been approved or recommended for this condition.KF-8 is a rice bran-derived anti-oxid...Dexamethasone is a common glucocorticoid medication with adverse effects that can cause muscle atrophy,but no drug intervention has been approved or recommended for this condition.KF-8 is a rice bran-derived anti-oxidant peptide that extends the lifespan of Caenorhabditis elegans.We established a C.elegans model of dexamethasone-induced myopathy to evaluate the potential therapeutic effects of KF-8 in this model.C.elegans muscle function was assessed in terms of locomotory behaviors including crawling,swimming,burrowing,pharyngeal pumping,and head swing.Muscle actin filament integrity was evaluated using fluorescence imaging.The molecular mechanisms of KF-8 were investigated using transcriptome sequencing,quantitative real-time PCR(qRT-PCR),RNA interference,and Western blot analysis.Dexamethasone disrupted actin filaments in the striated muscles of the body wall and inhibited C.elegans crawling,swimming,burrowing,pharyngeal pumping,and head swing.KF-8 reversed the actin filament disruption and locomotor dysfunction induced by dexamethasone.Transcriptome sequencing,pathway enrichment,and qRT-PCR analyses revealed that KF-8 regulated the locomotion-related genes W04G5.10,vha-12,and ddr-1,as well as age-1(the catalytic subunit ortholog of phosphatidylinositol 3-kinase(PI3K)),and akt1.RNA interference,conducted using a genetically engineered Escherichia coli HT115 strain as a food source,confirmed age-1 as a key regulator of locomotor function of C.elegans.Further mechanistic studies with C2C12 myotubes showed that KF-8 regulated the IRS-PI3K-Akt pathway,the master regulator of protein synthesis and degradation.Together,these findings suggest that KF-8 protects against dexamethasoneinduced myopathy in C.elegans by regulating locomotion-related genes and the IRS-PI3K-Akt pathway.展开更多
Background:Glucocorticoids are used as anti-inflammatory drugs for the treatment of various diseases,however,their side effects on normal brain tissue remain underinvestigated.Objectives:The study aimed to investigate...Background:Glucocorticoids are used as anti-inflammatory drugs for the treatment of various diseases,however,their side effects on normal brain tissue remain underinvestigated.Objectives:The study aimed to investigate dexamethasone(DXM)effects on cell composition and myelin content in the mouse brain tissue.Methods:C57Bl/6 male mice(n 60)received single and ten multiple intraperitoneal DXM injections(2.5 mg/kg),and the studied=parameters were analysed at 1,3,7,10 days after a single DXM injection and 15,30,60,and 90 days after the multiple injections.Oligodendrocytes,microglia,and astrocytes were assayed by immunohistochemistry with specific antibodies(Olig2,CD68,and GFAP,respectively)in the corpus callosum of the normal brain tissue.The myelin content was estimated by staining with LuxolFastBlue.The presence of GFAP isoforms was determined by western blotting.Results:DXM administration did not affect oligodendrocytes in the mouse brain but temporarily significantly decreased myelin content(1.2-fold,p 0.0058;1.4-fold,p 0.0001)at 3–15 days time points.At the same time,DXM significantly=<decreased the number of microglial cells(1.5–3.5-fold,p 0.0001)and significantly increased astrocytes(1.8-fold,p<<0.0001).Prolonged administration of DXM resulted in the decrease of the main GFAPα-isoform(50 kDa)and the appearance of shorter GFAP isoforms(30 kDa,42 kDa,44 kDa)similar to that in some neurodegenerative animal models.Conclusion:DXM can modify the cell composition of the normal mouse brain tissue by decreasing microglial cells and increasing astrocytes.Long-term use of DXM results in the inhibition of myelin formation and the appearance of truncated GFAP isoforms,suggesting its ability to induce neurodegeneration-like changes in the normal mouse brain.展开更多
ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX microcrystals(MCs)were prepared via precipitation,while LA-loaded porous P...ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX microcrystals(MCs)were prepared via precipitation,while LA-loaded porous PLGA microspheres(LPMPs)were fabricated using a double emulsion–solvent evaporation method.DEX MCs were physically perfused into LPMPs via negative pressure to form a combined system(DEX MCs+LPMPs).Physicochemical properties,in vitro drug release,pharmacokinetics,and biocompatibility were evaluated.Guinea pigs were used for intratympanic injections of DEX MCs,LPMPs,or DEX MCs+LPMPs.ResultsThe DEX MCs+LPMPs system enabled simultaneous release of both drugs,with DEX exhibiting superior pharmacokinetics(sustained perilymph concentrations up to 7 days)compared to DEX MCs alone.LA release from LPMPs demonstrated prolonged kinetics without burst release.SEM confirmed DEX MCs were localized within/on LPMPs and adhered to the round window membrane(RWM).Histological analysis revealed normal cochlear morphology and no inflammatory response,confirming biocompatibility.ConclusionsThis novel codelivery system combining microcrystals and porous microspheres achieves sustained dual-drug release,enhances therapeutic efficacy,and offers a promising strategy for managing hearing loss via intratympanic administration.展开更多
AIM:To investigate the efficacy and safety of repeated dexamethasone implants with real-life data in eyes with naive retinal vein occlusion(RVO)with macular edema(ME)at a minimum of 60mo follow-up.METHODS:In this retr...AIM:To investigate the efficacy and safety of repeated dexamethasone implants with real-life data in eyes with naive retinal vein occlusion(RVO)with macular edema(ME)at a minimum of 60mo follow-up.METHODS:In this retrospective cohort study,the data about best corrected visual acuity(BCVA),central macular thickness(CMT),serous macular detachment(SMD),hard exudate,hyperreflective foci(HRF),cystoid degeneration,pearl necklace sign,epiretinal membrane(ERM),disorganization of retinal inner layers(DRIL),ellipsoid zone and external limiting membrane(EZ-ELM)integrity,intraocular pressure(IOP)and lens condition were recorded.RESULTS:Thirty-eight eyes of 38 patients were included in the study.Thirteen patients presented with central RVO(CRVO)and 25 with branch RVO(BRVO).The mean follow-up time was 69.9±15.8mo,and the mean number of injections was 7.9±4.0.The mean BCVA gain was 25.0±36 letters,and this difference was statistically significant(P=0.021).The BCVA gain was 19.4±20.4 letters in the CRVO group,and 26.5±38.6 letters in the BRVO group(P=0.763).Besides,21(55.2%)of the patients achieved≥15 letters improvement.At the end of the follow-up period,SMD was not observed in any of the patients(P=0.016).Hard exudate,HRF number were decreased;while DRIL,ERM and EZ-ELM defects were increased but not significantly.CONCLUSION:Intravitreal dexamethasone monotherapy is an effective and safe treatment option for the treatment-naive RVO-ME patients in the long-term follow-up.展开更多
AIM:To evaluate the efficacy and safety of concurrent intravitreal ranibizumab(IVR)and extended-release dexamethasone injections(Dex-I)in naïve and refractory patients with retinal vein occlusion macular edema(RV...AIM:To evaluate the efficacy and safety of concurrent intravitreal ranibizumab(IVR)and extended-release dexamethasone injections(Dex-I)in naïve and refractory patients with retinal vein occlusion macular edema(RVO-ME).METHODS:This was a prospective,interventional,and open-label clinical trial.There were two groups:naïve and refractory patients(received≥5 times of previous IVR within one year prior to enrollment)enrolled.Patients received IVR and Dex-I concurrently and re-combination therapy was required if one or more retreatment criteria were met.IVR and Dex-I were given pro re nata(PRN).The mean changes in best-corrected visual acuity(BCVA)and central macular thickness(CMT)were measured as main outcomes.RESULTS:Totally 63 patients(63 eyes)completed the entire follow-up(31 naïve and 32 refractory patients).At month 12,the change in BCVA was greater in the naïve group than in the refractory group[19.67±11.7(95%CI:15.03,24.31)letters vs 11.74±11.18(95%CI:7.32,16.16)letters,P=0.014].There was no difference between the two groups of mean macular thickness reduction[364.26±215.29(95%CI:279.09,449.43)μm vs 410.19±204.34(95%CI:329.35,491.02)μm,P=0.43].The mean co-injection numbers were 2.52±0.58(95%CI:2.29,2.75)and 2.33±0.55(95%CI:2.11,2.55)in both groups(P=0.24),respectively.The retreatment interval was 115.81±13.79 d(95%CI:110.36,121.27)and 122.74±14.06 d(95%CI:119.93,133.56)in both groups(P=0.073).There was no significant difference in the incidence of glaucoma or the progression of cataracts between the two groups.CONCLUSION:In both naïve and refractory RVO-ME patients,IVR combined with Dex-I is effective.The initial combination therapy for naïve patients demonstrates more efficient improvement in BCVA and may reduce total injection numbers compared to refractory patients.展开更多
Using splenic cells of BALB/c mice infected with Friend Leukemia Virus (FVA) as a model of erythroid cells, we investigated the action of dexamethasone (Dex) to induce apoptosis of the cells in the presence of erythro...Using splenic cells of BALB/c mice infected with Friend Leukemia Virus (FVA) as a model of erythroid cells, we investigated the action of dexamethasone (Dex) to induce apoptosis of the cells in the presence of erythropoietin (EPO)——an apoptotic inhibitor in developing erythroid cells. The result indicated that after treatment with a certain range of Dex concentrations and prolonged incubation, the cells were characterized by the occurrence of DNA ladders which appeared on agarose electrophoresis. Transmission electron microscopy showed that karyopyknosis, chromatin condensation, dilatation of the perinuclear space, karyorrhexis, cytoplasmic vacuolization and cell fragmentation appeared in the cells depending on the dose of Dex and the treatment time. These results suggest that Dex could induce apoptosis in the developing erythroid cells as in other cells so far reported.展开更多
Objective:To investigate the protective effects and mechanisms of action of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis (SAP). Methods:The rats were divided into sha...Objective:To investigate the protective effects and mechanisms of action of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis (SAP). Methods:The rats were divided into sham-operated, model control, dexamethasone treated, and Salvia miltiorrhiza treated groups. At 3, 6, and 12 h after operation, the mortality rate of different groups, pathological changes, Bcl-2-associated X protein (Bax) and nuclear factor-κB (NF-κB) protein expression levels in multiple organs (the pancreas, liver, kidneys, and lungs), toll-like receptor 4 (TLR-4) protein levels (only in the liver), intercellular adhesion molecule 1 (ICAM-1) protein levels (only in the lung), and terminal deoxynucleotidy transferase mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining expression levels, as well as the serum contents of amylase, glutamate-pyruvate transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), blood urea nitrogen (BUN), and creatinine (CREA) were observed. Results:The mortality rate of the dexamethasone treated group was significantly lower than that of the model control group (P<0.05). The pathological changes in multiple organs in the two treated groups were relieved to different degrees (P<0.05 and P<0.01, respectively), the expression levels of Bax and NF-κB proteins, and apoptotic indexes of multiple organs were reduced (P<0.05 and P<0.01, respectively). The contents of amylase, GPT, GOT, BUN, and CREA in the two treated groups were significantly lower than those in model control groups (P<0.05 and P<0.01, respectively). The expression level of ICAM-1 protein in the lungs (at 3 and 12 h) in the dexamethasone treated group was significantly lower than that in the Salvia miltiorrhiza treated group (P<0.05). The serum contents of CREA (at 12 h) and BUN (at 6 h) of the Salvia miltiorrhiza treated group were significantly lower than those in the dexamethasone treated group (P<0.05). Conclusions:Both dexamethasone and Salvia miltiorrhiza can reduce the inflammatory reaction, regulate apoptosis, and thus protect multiple organs of rats with SAP.展开更多
In macrophages, the accumulation of cholesteryl esters synthesized by the activated acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1) results in the foam cell formation, a hallmark of early atherosclerotic lesions...In macrophages, the accumulation of cholesteryl esters synthesized by the activated acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1) results in the foam cell formation, a hallmark of early atherosclerotic lesions. In this study, with the treatment of a glucocorticoid hormone dexamethasone (Dex), lipid staining results clearly showed the large accumulation of lipid droplets containing cholesteryl esters in THP-1-derived macrophages exposed to lower concentration of the oxidized low-density lipoprotein (ox-LDL). More notably, when treated together with specific anti-ACAT inhibitors, the abundant cholesteryl ester accumulation was markedly diminished in THP-1-derived macrophages, confirming that ACAT is the key enzyme responsible for intracellular cholesteryl ester synthesis. RT-PCR and Western blot results indicated that Dex caused up-regulation of human ACAT1 expression at both the mRNA and protein levels in THP-1 and THP-1-derived macrophages. The luciferase activity assay demonstrated that Dex could enhance the activity of human ACAT1 gene P1 promoter, a major factor leading to the ACAT1 activation, in a cell-specific manner. Further experimental evidences showed that a glucocorticoid response element (GRE) located within human ACAT1 gene P1 promoter to response to the elevation of human ACAT1 gene expression by Dex could be functionally bound with glucocorticoid receptor (GR) proteins. These data supported the hypothesis that the clinical treatment with Dex, which increased the incidence of atherosclerosis, may in part due to enhancing the ACAT1 expression to promote the accumulation of cholesteryl esters during the macrophage-derived foam cell formation, an early stage of atherosclerosis.展开更多
AIM: To observe the therapeutic effects of dexamethasone on rats with severe acute pancreatitis (SAP) and investigate the influences of dexamethasone on the inflammatory mediators and NF-κB expression in multiple org...AIM: To observe the therapeutic effects of dexamethasone on rats with severe acute pancreatitis (SAP) and investigate the influences of dexamethasone on the inflammatory mediators and NF-κB expression in multiple organs of SAP rats as well as the mechanisms involved. METHODS: Ninety Sprague-Dawley (SD) rats with SAP were randomly divided into the model group (n = 45) and dexamethasone treatment group (n = 45), and another 45 rats were selected for the sham operation group. All groups were randomly subdivided into the 3 h, 6 h and 12 h groups, each group containing 15 rats. The survival of all groups and pathological changes of multiple organs (liver, kidney and lung) were observed at different time points after the operation. The pathologicalscore of multiple organs was carried out, followed by the determination of amylase, endotoxin and TNF-α contents in blood. The tissue microarray was used to detect the expression levels of NF-κB p65 protein in multiple organs. RESULTS: There was no marked difference between the model group and treatment group in the survival rate. The amylase content of the treatment group was significantly lower compared to the model group at 12 h (P < 0.01, 7791.00 vs 9195.00). Moreover, the endotoxin and TNF-α levels of the treatment group were significantly lower than that of the model group at 6 h and 12 h (P < 0.01, 0.040 vs 0.055, 0.042 vs 0.059 and P < 0.05, 58.30 vs 77.54, 38.70 vs 67.30, respectively). Regarding the changes in liver NF-κB expression, the model group significantly exceeded the sham operation group at 3 h (P < 0.01, 1.00 vs 0.00), and the treatment group significantly exceeded the sham operation group at 12 h (P < 0.01, 1.00 vs 0.00), whereas no marked difference was observed between the model group and treatment group at all time points. The kidney NF-κB expression level in the treatment group significantly exceeded the model group (P < 0.05, 2.00 vs 0.00) and the sham operation group (P < 0.01, 2.00 vs 0.00) at 12 h. No NF-κB expression in the lung was found in any group. CONCLUSION: Dexamethasone can lower the amylase, endotoxin and TNF-α levels as well as mortality of SAP rats. NF-κB plays an important role in multiple organ injury. Further studies should be conducted to determine whether dexamethasone can ameliorate the pathological changes of multiple organs by reducing the NF-κB expression in the liver and kidney. The advantages of tissue microarrays in pancreatitis pathological examination include time- and energy- saving, and are highly efficient and representative. The restriction of tissue microarrays on the representation of tissues to various extents due to small diameter may lead to the deviation of analysis.展开更多
AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP). METHODS: SAP rats were randomly assigned to the model group and tre...AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP). METHODS: SAP rats were randomly assigned to the model group and treatment group while the normal rats were assigned to the sham operation group. The mortality,ascite volumes,ascites/body weight ratio and pancreas pathological changes of all rats were observed at 3,6 and 12 h after operation. Their contents of amylase and endotoxin in plasma and contents of tumor necrosis factor (TNF-α),phospholipase A2 (PLA2) and IL-6 in serum were also determined. The microarray sections of their pancreatic tissues were prepared,terminal transferase dUTP nick end labeling (TUNEL) staining was performed and apoptotic indexes were calculated. RESULTS: There was no marked difference between treatment group and model group in survival. The contents of amylase and endotoxin in plasma and contents of TNF-α,PLA2 and IL-6 in serum,ascite volumes,ascites/body weight ratio and pancreas pathological scores were all lower in treatment group than in model group to different extents at different time points P < 0.05,58.3 (26.4) ng/L vs 77.535 (42.157) ng/L in TNF-α content,8.00 (2.00) points vs 9.00 (2.00) points in pathological score of pancreas respectively; P < 0.01,0.042 (0.018) EU/mL vs 0.056 (0.0195) EU/mL in endotoxin content,7791 (1863) U/L vs 9195 (1298) U/L in plasma amylase content,1.53 (0.79) vs 2.38 (1.10) in ascites/body weight ratio,8.00 (1.00) points vs 11.00 (1.50) points in pathological score of pancreas; P < 0.001,3.36 (1.56) ng/L vs 5.65 (1.08) ng/L in IL-6 content,4.50 (2.00) vs 7.20 (2.00),4.20 (1.60) vs 6.40 (2.30),3.40 (2.70) vs 7.90 (1.70) in ascite volumes,respectively. The apoptotic indexes of pancreas head and pancreas tail were all higher in treatment group than in model group at 6 h P < 0.01,0.00 (2.00)% vs 0.00 (0.00)%,0.20 (1.80) vs 0.00 (0.00) in apoptosis indexes,respectively. CONCLUSION: The mechanism of dexamethasone treatment in acute pancreatitis is related to its inhibition of inflammatory mediator generation and induction of pancreatic acinar cell apoptosis.展开更多
AIM:To elucidate the effects of dexamethasone on hypoxia-induced epithelial-to-mesenchymal transition(EMT) in colon cancer.METHODS:Human colon cancer HCT116 and HT29 cells were exposed to normoxic(21%) and hypoxic(1%)...AIM:To elucidate the effects of dexamethasone on hypoxia-induced epithelial-to-mesenchymal transition(EMT) in colon cancer.METHODS:Human colon cancer HCT116 and HT29 cells were exposed to normoxic(21%) and hypoxic(1%) conditions. First,the effect of dexamethasone on cell viability was examined by MTT cell proliferation assay. In order to measure the expression levels of EMT markers(Snail,Slug,Twist,E-cadherin,and integrin αVβ6) and hypoxia-related genes [Hypoxia-inducible factor-1α(HIF-1α) and vascular endothelial growth factor(VEGF)] by dexamethasone,quantitative real-time polymerase chain reaction and western blot analysis were performed. Furthermore,the morphological changes of colon cancer cells and the expression pattern of E-cadherin by dexamethasone were detected through immunocytochemistry. Finally,the effects of dexamethasone on the invasiveness and migration of colon cancer cells were elucidated using matrigel invasion,migration,and wound healing migration assays.RESULTS:Under hypoxia,dexamethasone treatment inhibited HIF-1α protein level and its downstream gene,VEGF m RNA level in the colon cancer cell lines,HCT116 and HT29. In addition,the presence of dexamethasone down-regulated the m RNA levels of hypoxia-induced Snail,Slug,and Twist,all transcriptional factors of EMT,as well as hypoxia-induced integrin αVβ6 protein level,a well-known EMT marker for colon cancer cells. Furthermore,reduced E-cadherin in hypoxic condition was found to be recoverable by treating with dexamethasone in both colon cancer cell lines. Similarly,under hypoxic conditions,dexamethasone restored the growth pattern and morphological phenotype reminiscent of colon cancer cells grown under normoxic conditions; dexamethasone blocked the migration and invasion of both colorectal cancer cell lines in hypoxia.CONCLUSION:Our study suggested that dexamethasone has inhibitory effects on cell migration and invasion by suppressing EMT of colon cancer cell lines in hypoxic condition.展开更多
AIM: To study the influence and mechanisms of dexamethasone on mesenteric lymph node of rats with severe acute pancreatitis (SAP). METHODS: The SAP rats were assigned to model, treated or sham-operated groups. The mor...AIM: To study the influence and mechanisms of dexamethasone on mesenteric lymph node of rats with severe acute pancreatitis (SAP). METHODS: The SAP rats were assigned to model, treated or sham-operated groups. The mortality, pathological changes of mesenteric lymph nodes, expression levels of NF-kB, P-selectin, Bax, Bcl-2 and caspase-3 protein and changes in apoptotic indexes in lymph nodes were observed at 3, 6 and 12 h after operation. The blood levels of endotoxin, superoxide dismutase (SOD), malondialdehyde (MDA), and endothelin-1 (ET-1) in blood were determined. RESULTS: SOD content, expression of Bax protein and apoptotic index were significantly higher in the treated group than in the model group at different time points (P < 0.05 or P < 0.01). Other blood-detecting indexes and histopathological scores of mesenteric lymphnodes were lower in the treated than in the model group (P < 0.05, P < 0.01 or P < 0.01). NF-kB protein expression was negative in all groups. Comparing P-selectin and caspase-3 expression levels among all three groups, there was no marked difference between the model and treated group. CONCLUSION: Dexamethasone can protect mesen-teric lymph nodes. The mechanism may be by reducing the content of inflammatory mediators in the blood and inducing lymphocyte apoptosis.展开更多
文摘Rheumatoid arthritis(RA)is a chronic autoimmune disease that affects approxi-mately 0.46%of the global population.Conventional therapeutics for RA,including disease-modifying antirheumatic drugs(DMARDs),nonsteroidal anti-inflammatory drugs(NSAIDs),and corticosteroids,frequently result in unintended adverse effects.Dexamethasone(DEX)is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive properties.Liposomal delivery of DEX,particu-larly when liposomes are surface-modified with targeting ligands like peptides or sialic acid,can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity.This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA.Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models,reduces joint inflammation and damage,and alleviates cartilage destruction compared to free DEX.The liposomal formulation also shows better hemocompatibility,fewer adverse effects on body weight and immune organ index,and a longer circulation time with higher bioavailability.The anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α(TNF-α)and B-cell-activating factor(BAFF),which are key players in the pathogenesis of RA.Additionally,liposomal DEX can induce the expres-sion of anti-inflammatory cytokines like interleukin-10(IL-10),which has significant anti-inflammatory and immunoregulatory properties.The findings suggest that lipo-somal DEX represents a promising candidate for effective and safe RA therapy,with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.
基金supported by research grants from the Ningbo Science and Technology Plan Project,No.2022Z143hezuo(to BL)the National Natural Science Foundation of China,No.82201520(to XD)。
文摘Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.
文摘Coronavirus disease 2019(COVID-19)is a contagious disease caused by severe acute respiratory syndrome coronavirus 2.It was declared a global pandemic on March 11,2020,by the World Health Organization.An excessive inflammatory response is a severe respiratory manifestation of COVID-19,which becomes predominant in later stages.Due to its immunosuppressive and anti-inflammatory properties,dexamethasone is the first systemic glucocorticoid to treat severe COVID-19 patients.This editorial reviews the efficacy and safety of highdose vs low-dose dexamethasone in patients with COVID-19.Findings indicate that using low-dose dexamethasone is beneficial and emphasize the need for additional research on the use of high-dose dexamethasone.While the study provides a robust evidence base,it is limited by the lack of long-term data,focus on specific outcomes and heterogeneity of the included studies.Future research should focus on the long-term effects of dexamethasone and its impact across varying disease severities and patient populations to refine treatment strategies and improve patient care.
文摘The ongoing coronavirus disease 2019(COVID-19)pandemic has necessitated rapid advancements in therapeutic strategies,with dexamethasone emerging as a key treatment for severe cases.This editorial discusses the systematic review conducted by Sethi et al,published in the World Journal of Virology.The review critically examines the efficacy and safety of varying dosages of dexamethasone in severe COVID-19 patients,providing a comprehensive meta-analysis that underscores the current clinical recommendations favoring a low-dose regimen.Despite these findings,the review highlights the potential benefits of tailored dosages for specific patient subgroups,suggesting a need for personalized treatment approaches.This editorial expands on the implications of these findings,advocating for the integration of evolving clinical data into treatment protocols and calling for further research into patient-specific responses to therapy.It emphasizes the importance of adaptability and precision in pandemic response,urging the medical community to consider both the robustness of existing evidence and the potential for innovative approaches to enhance patient outcomes in the face of global health challenges.
文摘Background: Intraperitoneal instillation (IPI) of local anesthesia was reported to reduce postoperative pain after laparoscopic surgeries. We aim to evaluate the effectiveness of IPI of bupivacaine + dexmedetomidine versus bupivacaine + dexamethasone on postoperative pain in patients undergoing laparoscopic cholecystectomy (LC). Methods: This randomized clinical trial was carried out on one hundred patients who underwent LC under general anesthesia. Patients were randomly divided into: Group (Dexa): IPI of bupivacaine with dexamethasone and Group (Dexmed): IPI of bupivacaine with dexmedetomidine. Results: The first time to request analgesia was significantly delayed in the dexmed group (P value Conclusions: Intraperitoneal Bupivacaine + Dexmedetomidine provided longer pain-free postoperative duration lower pain score over time, and lesser analgesic consumption.
基金Supported by Faculty of Medicine Vajira Hospital,Navamindradhiraj University Research Fund,No.1-67.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a major health concern in Thailand,with most patients diagnosed at the intermediate stage.Transarterial chemoembolization(TACE)is the standard treatment;however,postembolization syndrome(PES)remains a common complication.Although both dexamethasone(DEXA)and N-acetylcysteine(NAC)have shown efficacy in reducing PES,no study has directly compared their effects.AIM To compare the incidence of PES between DEXA and NAC in intermediate-stage HCC patients undergoing conventional TACE(cTACE).METHODS A randomized,double-blind,controlled trial was conducted at two tertiary hospitals in Thailand from November 2024 to April 2025.Eligible HCC patients(aged 18-70 years)were randomized(1:1)to receive either NAC(150 mg/kg/hour loading dose,followed by 50 mg/kg over 4 hours,then 6.25 mg/kg/hour for 48 hours post-cTACE)or DEXA(8 mg IV 1 hour before cTACE).cTACE was performed by blinded interventional radiologists.The primary outcome was PES occurrence within 48 hours,assessed using South West Oncology Group toxicity coding and the Common Terminology Criteria for Adverse Events.The secondary outcomes were post-cTACE liver decompensation and the dynamic changes in the albumin-bilirubin(ALBI)score.RESULTS A total of 56 intermediate-stage HCC patients were included(DEXA,n=28;NAC,n=28).Most had preserved liver function,with 92.9%classified as Child-Pugh A.The maximum tumor size was 6.2 cm,and 85.7%had multiple lesions.Additionally,39 patients(69.6%)met the beyond up-to-7 criteria.Overall,27 patients(48.2%)developed PES.After adjusting for confounding factors,the NAC group had a significantly lower incidence of PES than the DEXA group(32.1%vs 64.3%;adjusted odds ratio=0.17,95%confidence interval:0.03-0.87,P=0.033).Only two patients(3.6%)developed post-cTACE liver decompensation.Furthermore,51.8%patients experienced worsening ALBI scores within 48 hours post-procedure;however,the rate of ALBI score worsening did not significantly differ between the groups.CONCLUSION Compared with DEXA,NAC significantly reduces the incidence of PES,regardless of its impact on liver function recovery.Therefore,NAC is a preferable option for reducing PES in Barcelona Clinic Liver Cancer-B stage HCC patients with preserved liver function.
基金Tianjin Natural Science Foundation for Jingjinji Collaboration,Grant/Award Number:23JCZXJC00240Hebei Natural Science Foundation,Grant/Award Number:H2023201903+2 种基金Beijing Natural Science Foundation,Grant/Award Number:J230006Capital's Funds for Health Improvement and Research,Grant/Award Number:CFH:2022-2-5072CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-052。
文摘Background:Sudden sensorineural hearing loss(SSNHL),often associated with tinnitus,significantly impacts individuals'quality of life.Current treatments,such as free drugs via intravenous or intratympanic(IT)administration of dexamethasone(DEX)and lidocaine,face limitations like low bioavailability and rapid drug clearance.To address these challenges,we developed a local co-delivery system combining DEX microcrystals(DEX MCs)and lidocaine-loaded poly(lactic-co-glycolic acid)(PLGA)non-spherical microparticles(LPNMs)for sustained drug release in the inner ear.Methods:DEX MCs and LPNMs were prepared using the traditional precipitation technique and double emulsion-solvent evaporation,respectively.After characterizing physicochemical properties and drug release kinetics,they were dispersed in sodium hyaluronate solution for IT injection,then in vivo pharmacokinetics and biocompatibility in guinea pigs were studied.Results:DEX MCs exhibited stable dissolution,while LPNMs provided sustained lidocaine release,reducing potential side effects.In vivo studies in guinea pigs demonstrated prolonged drug retention in the perilymph and improved pharmacokinetics.Histological evaluation confirmed the good biocompatibility of this combined delivery system,with no significant inner ear damage observed.Conclusion:This co-delivery system can be used as a depot for delivering both DEX and lidocaine to the inner ear and offers a promising approach for the synergistic treatment of SSNHL associated with tinnitus.
基金Cultivation fund in Second Hospital of Shandong University(Grant No.2023YP11).
文摘Glucocorticoids are widely utilized for treating various immune and inflammation-related diseases,prompting significant interest in their potential application for COVID-19 treatment.This study explored the efficacy and safety of dexamethasone(DEX)and methylprednisolone(MP)in treating severe COVID-19.A cohort of 94 adult patients,aged 18 years and older,with severe COVID-19 was recruited.They received intravenous MP(40-80 mg/d)or DEX(5-10 mg/d)for 7-10 d.The primary objective was to assess the effects of these treatments on mortality rates.Additionally,the study aimed to compare the impact of these medications on various parameters,including the oxygenation index,inflammatory index,fungal infections,and hyperglycemia,serving as secondary endpoints.The findings revealed no fatalities in either group.However,there was one case of pulmonary fibrosis and Aspergillus fumigatus infection in the DEX group,and two cases of Aspergillus infection in the MP group.Although the differences were not statistically significant(P>0.05),the MP group showed a faster improvement in blood oxygen saturation compared to the DEX group,with a median time of 5 d vs 7 d.No statistically significant difference was observed between the two groups regarding improvement in C-reactive protein levels(P>0.05).Notably,DEX was associated with a higher incidence of hyperglycemia compared to MP(P<0.05).Both DEX and MP significantly reduced mortality rates among patients with severe COVID-19 and improved blood oxygen saturation and inflammatory markers.However,MP exhibited a more rapid onset of efficacy and fewer adverse reactions.
基金supported by funding from the National Key Research and Development Program of China(2022YFF1100203)National Natural Science Foundation of China(32372349)+1 种基金Science and Technology Innovation Talent Project of Hunan Province(2022RC3056)Key Research and Development Program of Hunan Province(2024AQ2020)。
文摘Dexamethasone is a common glucocorticoid medication with adverse effects that can cause muscle atrophy,but no drug intervention has been approved or recommended for this condition.KF-8 is a rice bran-derived anti-oxidant peptide that extends the lifespan of Caenorhabditis elegans.We established a C.elegans model of dexamethasone-induced myopathy to evaluate the potential therapeutic effects of KF-8 in this model.C.elegans muscle function was assessed in terms of locomotory behaviors including crawling,swimming,burrowing,pharyngeal pumping,and head swing.Muscle actin filament integrity was evaluated using fluorescence imaging.The molecular mechanisms of KF-8 were investigated using transcriptome sequencing,quantitative real-time PCR(qRT-PCR),RNA interference,and Western blot analysis.Dexamethasone disrupted actin filaments in the striated muscles of the body wall and inhibited C.elegans crawling,swimming,burrowing,pharyngeal pumping,and head swing.KF-8 reversed the actin filament disruption and locomotor dysfunction induced by dexamethasone.Transcriptome sequencing,pathway enrichment,and qRT-PCR analyses revealed that KF-8 regulated the locomotion-related genes W04G5.10,vha-12,and ddr-1,as well as age-1(the catalytic subunit ortholog of phosphatidylinositol 3-kinase(PI3K)),and akt1.RNA interference,conducted using a genetically engineered Escherichia coli HT115 strain as a food source,confirmed age-1 as a key regulator of locomotor function of C.elegans.Further mechanistic studies with C2C12 myotubes showed that KF-8 regulated the IRS-PI3K-Akt pathway,the master regulator of protein synthesis and degradation.Together,these findings suggest that KF-8 protects against dexamethasoneinduced myopathy in C.elegans by regulating locomotion-related genes and the IRS-PI3K-Akt pathway.
基金funded by the budgetary funding to FRC FTM for the project“Post-Genomic High-Tech Research on the Mechanisms of Development of Socially Significant Diseases and Stress-Induced Conditions”(Grant No.125031203556-7).
文摘Background:Glucocorticoids are used as anti-inflammatory drugs for the treatment of various diseases,however,their side effects on normal brain tissue remain underinvestigated.Objectives:The study aimed to investigate dexamethasone(DXM)effects on cell composition and myelin content in the mouse brain tissue.Methods:C57Bl/6 male mice(n 60)received single and ten multiple intraperitoneal DXM injections(2.5 mg/kg),and the studied=parameters were analysed at 1,3,7,10 days after a single DXM injection and 15,30,60,and 90 days after the multiple injections.Oligodendrocytes,microglia,and astrocytes were assayed by immunohistochemistry with specific antibodies(Olig2,CD68,and GFAP,respectively)in the corpus callosum of the normal brain tissue.The myelin content was estimated by staining with LuxolFastBlue.The presence of GFAP isoforms was determined by western blotting.Results:DXM administration did not affect oligodendrocytes in the mouse brain but temporarily significantly decreased myelin content(1.2-fold,p 0.0058;1.4-fold,p 0.0001)at 3–15 days time points.At the same time,DXM significantly=<decreased the number of microglial cells(1.5–3.5-fold,p 0.0001)and significantly increased astrocytes(1.8-fold,p<<0.0001).Prolonged administration of DXM resulted in the decrease of the main GFAPα-isoform(50 kDa)and the appearance of shorter GFAP isoforms(30 kDa,42 kDa,44 kDa)similar to that in some neurodegenerative animal models.Conclusion:DXM can modify the cell composition of the normal mouse brain tissue by decreasing microglial cells and increasing astrocytes.Long-term use of DXM results in the inhibition of myelin formation and the appearance of truncated GFAP isoforms,suggesting its ability to induce neurodegeneration-like changes in the normal mouse brain.
基金supported by Capital’s Funds for Health Improvement and Research(CFH:2022-2-5072)the Tianjin Natural Science Foundation for Jingjinji Collaboration(23JCZXJC00240)+1 种基金Beijing Natural Science Foundation(J230006)the CAMS Innovation Fund for Medical Science(2021-I2M-1-052).
文摘ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX microcrystals(MCs)were prepared via precipitation,while LA-loaded porous PLGA microspheres(LPMPs)were fabricated using a double emulsion–solvent evaporation method.DEX MCs were physically perfused into LPMPs via negative pressure to form a combined system(DEX MCs+LPMPs).Physicochemical properties,in vitro drug release,pharmacokinetics,and biocompatibility were evaluated.Guinea pigs were used for intratympanic injections of DEX MCs,LPMPs,or DEX MCs+LPMPs.ResultsThe DEX MCs+LPMPs system enabled simultaneous release of both drugs,with DEX exhibiting superior pharmacokinetics(sustained perilymph concentrations up to 7 days)compared to DEX MCs alone.LA release from LPMPs demonstrated prolonged kinetics without burst release.SEM confirmed DEX MCs were localized within/on LPMPs and adhered to the round window membrane(RWM).Histological analysis revealed normal cochlear morphology and no inflammatory response,confirming biocompatibility.ConclusionsThis novel codelivery system combining microcrystals and porous microspheres achieves sustained dual-drug release,enhances therapeutic efficacy,and offers a promising strategy for managing hearing loss via intratympanic administration.
文摘AIM:To investigate the efficacy and safety of repeated dexamethasone implants with real-life data in eyes with naive retinal vein occlusion(RVO)with macular edema(ME)at a minimum of 60mo follow-up.METHODS:In this retrospective cohort study,the data about best corrected visual acuity(BCVA),central macular thickness(CMT),serous macular detachment(SMD),hard exudate,hyperreflective foci(HRF),cystoid degeneration,pearl necklace sign,epiretinal membrane(ERM),disorganization of retinal inner layers(DRIL),ellipsoid zone and external limiting membrane(EZ-ELM)integrity,intraocular pressure(IOP)and lens condition were recorded.RESULTS:Thirty-eight eyes of 38 patients were included in the study.Thirteen patients presented with central RVO(CRVO)and 25 with branch RVO(BRVO).The mean follow-up time was 69.9±15.8mo,and the mean number of injections was 7.9±4.0.The mean BCVA gain was 25.0±36 letters,and this difference was statistically significant(P=0.021).The BCVA gain was 19.4±20.4 letters in the CRVO group,and 26.5±38.6 letters in the BRVO group(P=0.763).Besides,21(55.2%)of the patients achieved≥15 letters improvement.At the end of the follow-up period,SMD was not observed in any of the patients(P=0.016).Hard exudate,HRF number were decreased;while DRIL,ERM and EZ-ELM defects were increased but not significantly.CONCLUSION:Intravitreal dexamethasone monotherapy is an effective and safe treatment option for the treatment-naive RVO-ME patients in the long-term follow-up.
基金Supported by the National Nature Science Foundation of China(No.82301211)Beijing Natural Science Foundation(No.J230028).
文摘AIM:To evaluate the efficacy and safety of concurrent intravitreal ranibizumab(IVR)and extended-release dexamethasone injections(Dex-I)in naïve and refractory patients with retinal vein occlusion macular edema(RVO-ME).METHODS:This was a prospective,interventional,and open-label clinical trial.There were two groups:naïve and refractory patients(received≥5 times of previous IVR within one year prior to enrollment)enrolled.Patients received IVR and Dex-I concurrently and re-combination therapy was required if one or more retreatment criteria were met.IVR and Dex-I were given pro re nata(PRN).The mean changes in best-corrected visual acuity(BCVA)and central macular thickness(CMT)were measured as main outcomes.RESULTS:Totally 63 patients(63 eyes)completed the entire follow-up(31 naïve and 32 refractory patients).At month 12,the change in BCVA was greater in the naïve group than in the refractory group[19.67±11.7(95%CI:15.03,24.31)letters vs 11.74±11.18(95%CI:7.32,16.16)letters,P=0.014].There was no difference between the two groups of mean macular thickness reduction[364.26±215.29(95%CI:279.09,449.43)μm vs 410.19±204.34(95%CI:329.35,491.02)μm,P=0.43].The mean co-injection numbers were 2.52±0.58(95%CI:2.29,2.75)and 2.33±0.55(95%CI:2.11,2.55)in both groups(P=0.24),respectively.The retreatment interval was 115.81±13.79 d(95%CI:110.36,121.27)and 122.74±14.06 d(95%CI:119.93,133.56)in both groups(P=0.073).There was no significant difference in the incidence of glaucoma or the progression of cataracts between the two groups.CONCLUSION:In both naïve and refractory RVO-ME patients,IVR combined with Dex-I is effective.The initial combination therapy for naïve patients demonstrates more efficient improvement in BCVA and may reduce total injection numbers compared to refractory patients.
文摘Using splenic cells of BALB/c mice infected with Friend Leukemia Virus (FVA) as a model of erythroid cells, we investigated the action of dexamethasone (Dex) to induce apoptosis of the cells in the presence of erythropoietin (EPO)——an apoptotic inhibitor in developing erythroid cells. The result indicated that after treatment with a certain range of Dex concentrations and prolonged incubation, the cells were characterized by the occurrence of DNA ladders which appeared on agarose electrophoresis. Transmission electron microscopy showed that karyopyknosis, chromatin condensation, dilatation of the perinuclear space, karyorrhexis, cytoplasmic vacuolization and cell fragmentation appeared in the cells depending on the dose of Dex and the treatment time. These results suggest that Dex could induce apoptosis in the developing erythroid cells as in other cells so far reported.
基金Project (No. 2010382) supported by the Foundation for the Excellent Middle-Aged and Talented Young Persons of Zhejiang Province"151", China
文摘Objective:To investigate the protective effects and mechanisms of action of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis (SAP). Methods:The rats were divided into sham-operated, model control, dexamethasone treated, and Salvia miltiorrhiza treated groups. At 3, 6, and 12 h after operation, the mortality rate of different groups, pathological changes, Bcl-2-associated X protein (Bax) and nuclear factor-κB (NF-κB) protein expression levels in multiple organs (the pancreas, liver, kidneys, and lungs), toll-like receptor 4 (TLR-4) protein levels (only in the liver), intercellular adhesion molecule 1 (ICAM-1) protein levels (only in the lung), and terminal deoxynucleotidy transferase mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining expression levels, as well as the serum contents of amylase, glutamate-pyruvate transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), blood urea nitrogen (BUN), and creatinine (CREA) were observed. Results:The mortality rate of the dexamethasone treated group was significantly lower than that of the model control group (P<0.05). The pathological changes in multiple organs in the two treated groups were relieved to different degrees (P<0.05 and P<0.01, respectively), the expression levels of Bax and NF-κB proteins, and apoptotic indexes of multiple organs were reduced (P<0.05 and P<0.01, respectively). The contents of amylase, GPT, GOT, BUN, and CREA in the two treated groups were significantly lower than those in model control groups (P<0.05 and P<0.01, respectively). The expression level of ICAM-1 protein in the lungs (at 3 and 12 h) in the dexamethasone treated group was significantly lower than that in the Salvia miltiorrhiza treated group (P<0.05). The serum contents of CREA (at 12 h) and BUN (at 6 h) of the Salvia miltiorrhiza treated group were significantly lower than those in the dexamethasone treated group (P<0.05). Conclusions:Both dexamethasone and Salvia miltiorrhiza can reduce the inflammatory reaction, regulate apoptosis, and thus protect multiple organs of rats with SAP.
基金supported by grants of the Major State Basic Research Development program of China(No.2002CB513000)National Scienses Foudation Center(No.30393110)+1 种基金State Science and Technology Committee(SSTC)(NO.02DJ14068)Chinese Academy of Science to Bo Liang LI,and NIH grant HL36709 to Ta Yuan CHANG.
文摘In macrophages, the accumulation of cholesteryl esters synthesized by the activated acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1) results in the foam cell formation, a hallmark of early atherosclerotic lesions. In this study, with the treatment of a glucocorticoid hormone dexamethasone (Dex), lipid staining results clearly showed the large accumulation of lipid droplets containing cholesteryl esters in THP-1-derived macrophages exposed to lower concentration of the oxidized low-density lipoprotein (ox-LDL). More notably, when treated together with specific anti-ACAT inhibitors, the abundant cholesteryl ester accumulation was markedly diminished in THP-1-derived macrophages, confirming that ACAT is the key enzyme responsible for intracellular cholesteryl ester synthesis. RT-PCR and Western blot results indicated that Dex caused up-regulation of human ACAT1 expression at both the mRNA and protein levels in THP-1 and THP-1-derived macrophages. The luciferase activity assay demonstrated that Dex could enhance the activity of human ACAT1 gene P1 promoter, a major factor leading to the ACAT1 activation, in a cell-specific manner. Further experimental evidences showed that a glucocorticoid response element (GRE) located within human ACAT1 gene P1 promoter to response to the elevation of human ACAT1 gene expression by Dex could be functionally bound with glucocorticoid receptor (GR) proteins. These data supported the hypothesis that the clinical treatment with Dex, which increased the incidence of atherosclerosis, may in part due to enhancing the ACAT1 expression to promote the accumulation of cholesteryl esters during the macrophage-derived foam cell formation, an early stage of atherosclerosis.
基金Technological Foundation Project of Traditional Chinese Medicine Science of Zhejiang Province, NO. 2003C130 and NO. 2004C142 Foundation Project for Medical Science and Technology of Zhejiang province, No. 2003B134+3 种基金 Grave Foundation Project for Technological and Development of Hangzhou, No. 2003123B19 Intensive Foundation Project for Technology of Hangzhou, NO. 2004Z006 Foundation Project for Medical Science and Technology of Hangzhou, No. 2003A004 and Foundation Project for Technology of Hangzhou, No. 2005224
文摘AIM: To observe the therapeutic effects of dexamethasone on rats with severe acute pancreatitis (SAP) and investigate the influences of dexamethasone on the inflammatory mediators and NF-κB expression in multiple organs of SAP rats as well as the mechanisms involved. METHODS: Ninety Sprague-Dawley (SD) rats with SAP were randomly divided into the model group (n = 45) and dexamethasone treatment group (n = 45), and another 45 rats were selected for the sham operation group. All groups were randomly subdivided into the 3 h, 6 h and 12 h groups, each group containing 15 rats. The survival of all groups and pathological changes of multiple organs (liver, kidney and lung) were observed at different time points after the operation. The pathologicalscore of multiple organs was carried out, followed by the determination of amylase, endotoxin and TNF-α contents in blood. The tissue microarray was used to detect the expression levels of NF-κB p65 protein in multiple organs. RESULTS: There was no marked difference between the model group and treatment group in the survival rate. The amylase content of the treatment group was significantly lower compared to the model group at 12 h (P < 0.01, 7791.00 vs 9195.00). Moreover, the endotoxin and TNF-α levels of the treatment group were significantly lower than that of the model group at 6 h and 12 h (P < 0.01, 0.040 vs 0.055, 0.042 vs 0.059 and P < 0.05, 58.30 vs 77.54, 38.70 vs 67.30, respectively). Regarding the changes in liver NF-κB expression, the model group significantly exceeded the sham operation group at 3 h (P < 0.01, 1.00 vs 0.00), and the treatment group significantly exceeded the sham operation group at 12 h (P < 0.01, 1.00 vs 0.00), whereas no marked difference was observed between the model group and treatment group at all time points. The kidney NF-κB expression level in the treatment group significantly exceeded the model group (P < 0.05, 2.00 vs 0.00) and the sham operation group (P < 0.01, 2.00 vs 0.00) at 12 h. No NF-κB expression in the lung was found in any group. CONCLUSION: Dexamethasone can lower the amylase, endotoxin and TNF-α levels as well as mortality of SAP rats. NF-κB plays an important role in multiple organ injury. Further studies should be conducted to determine whether dexamethasone can ameliorate the pathological changes of multiple organs by reducing the NF-κB expression in the liver and kidney. The advantages of tissue microarrays in pancreatitis pathological examination include time- and energy- saving, and are highly efficient and representative. The restriction of tissue microarrays on the representation of tissues to various extents due to small diameter may lead to the deviation of analysis.
基金Supported by Grants for Traditional Chinese Medicine Science of Zhejiang Province,and Medical Science and Technology of Zhejiang Province and Hangzhou
文摘AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP). METHODS: SAP rats were randomly assigned to the model group and treatment group while the normal rats were assigned to the sham operation group. The mortality,ascite volumes,ascites/body weight ratio and pancreas pathological changes of all rats were observed at 3,6 and 12 h after operation. Their contents of amylase and endotoxin in plasma and contents of tumor necrosis factor (TNF-α),phospholipase A2 (PLA2) and IL-6 in serum were also determined. The microarray sections of their pancreatic tissues were prepared,terminal transferase dUTP nick end labeling (TUNEL) staining was performed and apoptotic indexes were calculated. RESULTS: There was no marked difference between treatment group and model group in survival. The contents of amylase and endotoxin in plasma and contents of TNF-α,PLA2 and IL-6 in serum,ascite volumes,ascites/body weight ratio and pancreas pathological scores were all lower in treatment group than in model group to different extents at different time points P < 0.05,58.3 (26.4) ng/L vs 77.535 (42.157) ng/L in TNF-α content,8.00 (2.00) points vs 9.00 (2.00) points in pathological score of pancreas respectively; P < 0.01,0.042 (0.018) EU/mL vs 0.056 (0.0195) EU/mL in endotoxin content,7791 (1863) U/L vs 9195 (1298) U/L in plasma amylase content,1.53 (0.79) vs 2.38 (1.10) in ascites/body weight ratio,8.00 (1.00) points vs 11.00 (1.50) points in pathological score of pancreas; P < 0.001,3.36 (1.56) ng/L vs 5.65 (1.08) ng/L in IL-6 content,4.50 (2.00) vs 7.20 (2.00),4.20 (1.60) vs 6.40 (2.30),3.40 (2.70) vs 7.90 (1.70) in ascite volumes,respectively. The apoptotic indexes of pancreas head and pancreas tail were all higher in treatment group than in model group at 6 h P < 0.01,0.00 (2.00)% vs 0.00 (0.00)%,0.20 (1.80) vs 0.00 (0.00) in apoptosis indexes,respectively. CONCLUSION: The mechanism of dexamethasone treatment in acute pancreatitis is related to its inhibition of inflammatory mediator generation and induction of pancreatic acinar cell apoptosis.
基金Supported by A grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institutefunded by the Ministry of Health&Welfare,Republic of Korea,No.HI13C-1602-010014)grants of the Gachon University Gil Medical Center,No.2013-01,2014-11 and 2014-25
文摘AIM:To elucidate the effects of dexamethasone on hypoxia-induced epithelial-to-mesenchymal transition(EMT) in colon cancer.METHODS:Human colon cancer HCT116 and HT29 cells were exposed to normoxic(21%) and hypoxic(1%) conditions. First,the effect of dexamethasone on cell viability was examined by MTT cell proliferation assay. In order to measure the expression levels of EMT markers(Snail,Slug,Twist,E-cadherin,and integrin αVβ6) and hypoxia-related genes [Hypoxia-inducible factor-1α(HIF-1α) and vascular endothelial growth factor(VEGF)] by dexamethasone,quantitative real-time polymerase chain reaction and western blot analysis were performed. Furthermore,the morphological changes of colon cancer cells and the expression pattern of E-cadherin by dexamethasone were detected through immunocytochemistry. Finally,the effects of dexamethasone on the invasiveness and migration of colon cancer cells were elucidated using matrigel invasion,migration,and wound healing migration assays.RESULTS:Under hypoxia,dexamethasone treatment inhibited HIF-1α protein level and its downstream gene,VEGF m RNA level in the colon cancer cell lines,HCT116 and HT29. In addition,the presence of dexamethasone down-regulated the m RNA levels of hypoxia-induced Snail,Slug,and Twist,all transcriptional factors of EMT,as well as hypoxia-induced integrin αVβ6 protein level,a well-known EMT marker for colon cancer cells. Furthermore,reduced E-cadherin in hypoxic condition was found to be recoverable by treating with dexamethasone in both colon cancer cell lines. Similarly,under hypoxic conditions,dexamethasone restored the growth pattern and morphological phenotype reminiscent of colon cancer cells grown under normoxic conditions; dexamethasone blocked the migration and invasion of both colorectal cancer cell lines in hypoxia.CONCLUSION:Our study suggested that dexamethasone has inhibitory effects on cell migration and invasion by suppressing EMT of colon cancer cell lines in hypoxic condition.
基金Technological Foundation Project of Traditional Chinese Medicine Science of Zhejiang Province, No. 2003C130 and No. 2004C142Foundation Project for Medical Science and Technology of Zhejiang Province, No. 2003B134+5 种基金Grave Foundation Project for Technological and Development of Hangzhou, No. 2003123B19Intensive Foundation Project for Technology of Hangzhou No. 2004Z006Foundation Project for Medical Science and Technology of Hangzhou No. 2003A004Foundation Project for Technology of Hangzhou, No. 2005224
文摘AIM: To study the influence and mechanisms of dexamethasone on mesenteric lymph node of rats with severe acute pancreatitis (SAP). METHODS: The SAP rats were assigned to model, treated or sham-operated groups. The mortality, pathological changes of mesenteric lymph nodes, expression levels of NF-kB, P-selectin, Bax, Bcl-2 and caspase-3 protein and changes in apoptotic indexes in lymph nodes were observed at 3, 6 and 12 h after operation. The blood levels of endotoxin, superoxide dismutase (SOD), malondialdehyde (MDA), and endothelin-1 (ET-1) in blood were determined. RESULTS: SOD content, expression of Bax protein and apoptotic index were significantly higher in the treated group than in the model group at different time points (P < 0.05 or P < 0.01). Other blood-detecting indexes and histopathological scores of mesenteric lymphnodes were lower in the treated than in the model group (P < 0.05, P < 0.01 or P < 0.01). NF-kB protein expression was negative in all groups. Comparing P-selectin and caspase-3 expression levels among all three groups, there was no marked difference between the model and treated group. CONCLUSION: Dexamethasone can protect mesen-teric lymph nodes. The mechanism may be by reducing the content of inflammatory mediators in the blood and inducing lymphocyte apoptosis.
