Dosage and utilization of dexamethasone in the management of COVID-19: A critical review

BACKGROUND The severe respiratory manifestations observed in severe coronavirus disease 2019(COVID-19)cases are often associated with an excessive inflammatory response.Dexamethasone,a synthetic glucocorticoid,exerts its anti-inflammatory effects by inhibiting the transcription of pro-inflammatory genes and suppressing the activity of various immune cells.This mechanism has implications for mitigating the cytokine storm observed in severe COVID-19 cases.Early on in the pandemic,the Recovery Collaborative working group showed a mortality benefit of using dexamethasone in decreasing mortality in patients with COVID-19 requiring respiratory support.However,the optimal dosage of corticosteroids remains debatable.Several studies that compare different doses of dexamethasone in COVID-19 exist,but the results are conflicting.AIM To review the latest evidence regarding dosage,safety,and efficacy of dexamethasone in severe COVID-19.METHODS We followed preferred reporting items for systematic reviews and meta-analysis guidelines.A detailed literature search was conducted across PubMed,Google Scholar,and Medline to include publications up to March 2024.Our keywords included“COVID-19”“SARS-CoV-2”“dexamethasone”“corticosteroid”“steroid”and“glucocorticoid”-along with their combinations.We employed the Cochrane Risk of Bias Tool and the Newcastle-Ottawa scale to evaluate the integrity and potential of bias in the included studies.A meta-analysis was conducted using a random-effects model,assessing pooled odds ratios and mean differences,with heterogeneity gauged by the I2 statistic and theχ^(2) tests.RESULTS No statistical differences were found in 28-day all-cause mortality[pooled odds ratio(OR)=1.109,95%CI:0.918-1.340],60-day all-cause mortality(OR=0.873,95%CI:0.744-1.024;I2=47.29%),mean length of hospital stay(mean difference=-0.08 days,95%CI:-0.001 to 0.161)and adverse events(OR=0.877,95%CI:0.707-1.087).CONCLUSION Differing doses of corticosteroids have no clinical implications on mortality,mean length of hospital stay,and adverse events in COVID-19 patients.Additional research is required in patients requiring invasive or noninvasive ventilation.

Unveiling osteoprotective potential of biologically active naringenin in rats with dexamethasone-induced osteoporosis

Objective To investigate the protective effects of naringenin(NRG)against dexamethasone(DEX)-induced osteoporosis(OP)in rats.Methods Molecular docking of NRG was done with AutoDock Vina 1.2.0 software.Forty-eight female Wistar rats were randomly divided into six groups(n=8 each):normal control(NC),DEX(7 mg/kg,i.m.),NRG-low(NRG-L;25 mg/kg,i.g.),NRG-medium(NRG-M;50 mg/kg,i.g.),NRG-high(NRG-H;100 mg/kg,i.g.),and alendronate(ALN;0.25 mg/d,i.g.)groups.OP was induced by administering DEX once a week for five weeks in all groups except NC group.Begining in the third week after the initial DEX administration,the rats in NRG-L,NRG-M,NRG-H,and ALN groups received the corresponding treatments daily for three weeks,while NC and DEX groups received no additional treatment.Serum samples were collected at the end of the experiment for biochemical,bone turnover,antioxidant,lipid profile,and inflammatory cytokine analyses.Femur bones underwent physical parameter testing and histopathological examination.Results The molecular docking results illustrated that NRG docked with calcitonin(CT),lowdensity lipoprotein(LDL),bone morphogenetic protein(BMP),vascular endothelial growth factor(VEGF)receptor,forkhead transcription factors,and osteoprogenitor cells showed good binding energy.In rats administered with 25,50,and 100 mg/kg NRG,there was a significant enhancement in serum biochemical indices,characterized by a reduction in tartrate-resistant acid phosphatase(TRAP),parathyroid hormone(PTH),and an elevation in osteocalcin(OC)and CT levels(P<0.05,P<0.01,and P<0.001,respectively).Despite no significant changes in thickness,weight,and length(P>0.05),there was a marked increase in bone mineral density(BMD)(P<0.01,P<0.001,and P<0.001,respectively).Antioxidant enzyme markers showed significant upregulation,with higher glutathione,superoxide dismutase,and catalase,and a concurrent decrease in malondialdehyde(MDA)(P<0.05,P<0.01,and P<0.001,respectively).The lipid profile also improved significantly,with lower cholesterol(CH),triglycerides(TG),and low-density lipoprotein(LDL)levels,and an increase in high-density lipoprotein(HDL)level(P<0.05,P<0.01,and P<0.001,respectively).Inflammatory cytokine levels were reduced,as evidenced by decreases in tumor necrosis factor(TNF),interleukin(IL)-6,and IL-1β(P<0.05,P<0.01,and P<0.001,respectively).Furthermore,histological alterations revealed obvious improvements,and the body weight of rats treated with NRG showed an increase compared with DEX group.Conclusion These findings imply that NRG exhibited a protective effect against DEX-induced OP in rats as it promotes the bone formation process by increasing the number of bone turnover markers including OC and CT,and restoring of antioxidant status,lipid metabolism,and inflammatory markers.

Dexamethasone implant in naive versus refractory patients with diabetic macular edema:a Meta-analysis

AIM:To evaluate the efficacy and safety of the intravitreal dexamethasone implant in naive and refractory patients with diabetic macular edema(DME).METHODS:PubMed,Embase,Web of Science,and Medline databases were searched.The main outcomes were best-corrected visual acuity(BCVA)and central retinal thickness(CRT).The secondary outcomes included mean number of injections,intraoperative or postoperative complications including intraocular pressure(IOP)elevation and cataract.RESULTS:Ten comparative studies involving a total of 1000 DME eyes including 402 naive eyes and 598 refractory eyes were selected.The postoperative BCVA in the naive group was significantly better than in the refractory group[mean difference(MD)-0.11,95% confidence interval(CI)-0.17 to-0.05,P=0.0003;MD 8.69,95%CI 5.08 to 12.30,P<0.00001].Additionally,the naive group got greater improvement of BCVA change as well as more gains of BCVA letters than the refractory group[MD 7.71,95%CI 2.02 to 13.40,P=0.008;odds ratio(OR)2.99,95%CI 2.05 to 4.37,P<0.00001].The subgroup analysis revealed that the naive group had significantly higher BCVA gains of≥5,≥10,and≥15 letters compared to the refractory group(P=0.002,0.0001,0.003,respectively).No significant difference was detected between the two groups in either postoperative CRT(MD-22.36,95%CI-46.39 to 1.66,P=0.07)or the overall mean number of injections(MD-0.08,95%CI-0.38 to 0.22,P=0.61).Intraoperative and postoperative complications including the elevation of IOP(OR 0.47,95%CI 0.20 to 1.13,P=0.09)and cataract(OR 1.78,95%CI 0.97 to 3.24,P=0.06)showed no significant differences between the two groups during the follow-up time.CONCLUSION:Intravitreal dexamethasone implants for DME can improve anatomical and functional outcomes in both naive and refractory eyes and have a well-acceptable safety profile.Moreover,naive eyes maintain better visual outcomes than refractory eyes.It provides further evidence of better visual response when used for naive eyes as firstline therapy.

Dexamethasone implant for refractory macular edema secondary to diabetic retinopathy and retinal vein occlusion

AIM:To evaluate the efficacy,timing of retreatment and safety of dexamethasone(DEX)implant on macular edema(ME)secondary to diabetic retinopathy(DME)and retinal vein occlusion(RVO-ME)patients who were refractory to anti-vascular endothelial growth factor(VEGF)treatment.METHODS:This retrospective study included 37 eyes received at least one DEX implant treatment for DME or RVO-ME between January 1,2019,and January 1,2023.These refractory DME and RVO-ME cases received at least 5 anti-VEGF injections and failure to gain more than 5 letters or a significant reduction in central retinal thickness(CRT).The best corrected visual acuity(BCVA)and CRT were measured at baseline,and at 1,3,4 and 6mo post-DEX implant injection.Adverse events such as elevated intraocular pressure(IOP)and cataract were recorded.RESULTS:For RVO cases(n=22),there was a significant increase in BCVA from 0.27±0.19 to 0.35±0.20 at 6mo post-DEX injection(P<0.05)and CRT decreased from 472.1±90.6 to 240.5±39.0μm at 6mo(P<0.0001).DME cases(n=15)experienced an improvement in BCVA from 0.26±0.15 to 0.43±0.20 at 6mo post-DEX implant injection(P=0.0098),with CRT reducing from 445.7±55.7 to 271.7±34.1μm at 6mo(P<0.0001).Elevated IOP occurred in 45.9% of patients but was well-controlled with topical medications.No cases of cataract or other adverse events were reported.CONCLUSION:DEX implants effectively improve BCVA and reduce CRT in refractory DME and RVO-ME.Further research with larger cohorts and longer follow-up periods is needed to confirm these findings and assess long-term outcomes.

Exploration of standard dosage for GnRH antagonist protocol and dosage adjustments after premature luteinizing hormone surge

The gonadotropin-releasing hormone (GnRH) antagonist protocol has emerged as an efficacious alternative to the GnRH agonist protocol for controlled ovarian hyperstimulation (COH) during in vitro fertilization (IVF) cycles, and has been demonstrated applicability in infertile female patients with diverse ovarian responses. While the clinical implementation of the antagonist COH protocol has achieved widespread consensus, opportunities for refinement persist. Therefore, this review article focuses on the advantages and disadvantages of GnRH antagonist protocol, the selection of optimal standard doses, and the strategies for adjusting antagonist doses after the premature luteinizing hormone (LH) surge, aiming to provide more reasonable and scientific recommendations for the application of this scheme.

Comparative evaluation of artificial intelligence systems'accuracy in providing medical drug dosages:A methodological study

BACKGROUND Medication errors,especially in dosage calculation,pose risks in healthcare.Artificial intelligence(AI)systems like ChatGPT and Google Bard may help reduce errors,but their accuracy in providing medication information remains to be evaluated.AIM To evaluate the accuracy of AI systems(ChatGPT 3.5,ChatGPT 4,Google Bard)in providing drug dosage information per Harrison's Principles of Internal Medicine.METHODS A set of natural language queries mimicking real-world medical dosage inquiries was presented to the AI systems.Responses were analyzed using a 3-point Likert scale.The analysis,conducted with Python and its libraries,focused on basic statistics,overall system accuracy,and disease-specific and organ system accuracies.RESULTS ChatGPT 4 outperformed the other systems,showing the highest rate of correct responses(83.77%)and the best overall weighted accuracy(0.6775).Disease-specific accuracy varied notably across systems,with some diseases being accurately recognized,while others demonstrated significant discrepancies.Organ system accuracy also showed variable results,underscoring system-specific strengths and weaknesses.CONCLUSION ChatGPT 4 demonstrates superior reliability in medical dosage information,yet variations across diseases emphasize the need for ongoing improvements.These results highlight AI's potential in aiding healthcare professionals,urging continuous development for dependable accuracy in critical medical situations.

High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

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.

Treatment Efficacy and Safety of Bortezomib Combined with Dexamethasone and Lenalidomide Chemotherapy Regimen for Multiple Myeloma

Objective:To analyze the effect of bortezomib combined with dexamethasone and lenalidomide in the treatment of multiple myeloma.Methods:60 cases of multiple myeloma patients admitted to our hospital from January 2022 to December 2023 were selected randomly,with 30 cases in each group.Bortezomib combined with dexamethasone was administered in the control group,and bortezomib combined with dexamethasone and lenalidomide was given to the observation group,and the treatment effect was analyzed.Results:After treatment,CD^(3+)and CD^(4+)of the observation group were higher than that of the control group,CD^(8+)was lower than that of the control group,and the total treatment efficiency was higher,which was statistically significant(P<0.05),and there was no difference in the total incidence of adverse reactions between the two groups(P>0.05).Conclusion:Bortezomib combined with dexamethasone and lenalidomide is effective in the treatment of multiple myeloma as it regulates the immune function and is safe,thus it can be promoted in clinical practice.

A spotlight on dosage and subject selection for effective neuroprotection: exploring the central role of mitochondria

Neurons are notoriously vulnerable cell types.Even the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper function.In most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell death.The challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological conditions.Such interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical levels.In this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective treatments.These are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.

Observation of the Curative Effect of the Dexamethasone Vitreous Cavity Implant for the Treatment of Irvine-Gass Syndrome

Objective To investigate the clinical efficacy of dexamethasone vitreous cavity implants(Ozurdex)for the treatment of macular edema(Irvine-Gass Syndrome)after cataract surgery.Method Eight patients(eight eyes)with Irvine-Gass syndrome were enrolled for vitreous injections with Ozurdex.The patients included six men(six eyes)and two women(two eyes)with a mean age of 67.12±11.92 years.Changes in the patients best-corrected visual acuity(BCVA),central macular thickness(CMT),and intraocular pressure were compared before and after treatment.Result The mean visual acuity BCVA of the patients was 0.81±0.26 before implantation,which improved to 0.20±0.12,0.13±0.09,and 0.15±0.13 at 2 weeks,1 month,and 3 months after implantation,respectively(P<0.001).The patient’s mean CMT before implantation was 703.00±148.88μm,and it reduced to 258.87±37.40μm,236.25±28.74μm,and 278.00±76.82μm at 2 weeks,1 month,and 3 months after implantation,respectively(P<0.001).Conclusion The dexamethasone vitreous cavity implant(Ozurdex)is a safe and effective treatment,which can effectively improve patient’s visual acuity and reduce macular edema associated with cataract surgery.

Dexamethasone potentiates the insulin-induced Srebp-1c expression in primary rat hepatocytes

The impacts of dexamethasone(Dex)and thyroid hormone T3 on the insulin-stimulated Srebp-1c expression were studied in primary rat hepatocytes. Primary hepatocytes from Sprague-Dawley rats were isolated, cultured and treated with insulin in the presence or absence of the indicated reagents over time. The mRNA levels of indicated genes were determined using real-time PCR. Insulin treatment induced the Srebp-1c expression and suppressed the Pck1 expression in a time-dependent manner. Dex treatment alone reduced the Srebp-1c expression, whereas potentiated the insulin-induced its expression, which reached to a level that was higher than the insulin alone group. On the other hand, insulin treatment completely suppressed the Dex-induced Pck1 expression in the same cells. T3 treatment did not affect the expressions of Srebp-1c and Pck1 alone or in the presence of absence of insulin or Dex. Interestingly, insulin treatment induced the Rxrg m RNA expression level in the absence or presence of T0901317, a specific agonist for the liver X receptor. Dex and insulin mutually affect each other's ability to regulate the expression levels of hepatic genes involved in glucose and fatty acid metabolism. Insulin induced Rxrg expression in primary hepatocytes, which may contribute to the induction of Srebp-1c expression in the same cells.

Combination of cataract surgery with intravitreal injection of dexamethasone intravitreal implant(Ozurdex)for uveitis-induced cataract

AIM:To evaluate the long-term results of patients with chronic uveitis-induced cataract by phacoemulsification with IOL implantation and intravitreal injection of dexamethasone(DEX)intravitreal implant(Ozurdex).METHODS:The study included 32 eyes of 26 patients treated with DEX implant due to chronic uveitis-induced cataract and followed up for at least a year.Best-corrected visual acuity(BCVA),intraocular pressure(IOP),anterior chamber reaction,central macular thickness(CMT),intraoperative and postoperative complications and uveitis recurrence were analyzed retrospectively.RESULTS:A successful surgery was performed in all patients.The average follow-up period was 12mo.The female/male ratio was 13/13.Mean age was 45.65±3.83y(range 26 to 65y).Etiologically,rheumatic arthritis occurred in 6 patients(18.75%),ankylosing spondylitis in 4(12.50%),HLA-B27 associated uveitis in 3(9.38%),Vogt-KoyanagiHarada-associated uveitis in 4(12.50%),Behcet’s disease in 2(6.25%),and 7(21.88%)suffered from unknown diseases.All 32 eyes had varying degrees of improvement at 12mo after surgery,with 2 eyes showing BCVA of 0.1 or below(6.25%),6 having 0.1-0.5(18.75%),18 of 0.5-1.0(56.25%),and 6 of 1.0 or above(18.75%).No cases with increased IOP were observed.The values of mean CMT was increased at day 1,decreased at 1,3mo after surgery and increased at 6,12mo after surgery.No severe uveitis reactions,such as fibrinous exudates in the anterior chamber and exudative membrane formation on the anterior surface of the IOL,were observed after surgery.CONCLUSION:The present studies show that intravitreal injection of Ozudex during cataract operation can provide a new option for the clinical treatment of uveitis-induced cataract.

The therapeutic mechanism of dexamethasone in lung injury induced by hydrogen sulfide

The lung is one of the primary target organs of hydrogen sulfide(H2S),as exposure to H2S can cause acute lung injury(ALI)and pulmonary edema.Dexamethasone(Dex)exerts a protective effect on ALI caused by exposure to toxic gases and is commonly used in the clinic;however,the underlying mechanisms remain elusive,and the dose is unclear.Methods:In vivo experiments:divided C57BL6 mice into 6 groups at random,12 in each group.The mice were exposed to H2S for 3 h and 5 or 50 mg/kg Dex pretreated before exposure,sacrificed 12 h later.The morphological changes of HE staining and the ultrastructural changes of lungs under transmission electron microscopy were evaluated.The wet/dry ratio of lung tissue was measured.Bronchial alveolar lavage fluid(BALF)protein content and lung permeability index were detected.The expression of AQP5 protein was measured by immunohistochemistry and Western Blot(WB).In vitro experiments:divided human lung adenocarcinoma cell line A549 into 4 groups.1μmol/L dexamethasone was added to pre-incubation.The WB analyzed the protein of p-ERK1/2,p-JNK,and p-p38 in MAPK pathway after 1 h of NaHS exposure;six hours after NaHS exposure,the AQP5 protein was measured by WB.Results:Dex treatment could significantly attenuate the H2S-induced destruction to the alveolar wall,increase the wet-to-dry weight ratio and decrease pulmonary permeability index,with high-dose dexamethasone seemingly functioning better.Additionally,our previous studies showed that aquaporin 5(AQP 5),a critical protein that regulates water flux,decreased both in a mouse and cell model following the exposure to H2S.This study indicates that tThe decrease in AQP 5 can be alleviated by Dex treatment.Additionally,the mitogen activated protein kinase(MAPK)pathway may be involved in the protective effects of Dex in ALI caused by exposure to H2S since H2Sinduced MAPK activation could be inhibited by Dex.Conclusion:The present results indicate that AQP 5 may be considered a therapeutic target for Dex in H2S or other hazardous gases-induced ALI.

The Effect of Dexamethasone versus Methylprednisolone in the Treatment of COVID-19 Patients in Jordan

Background: Previous studies focused on the treatment effect of steroids versus no steroids in treating severe COVID-19 patients, a few studies evaluated outcomes for treating those patients with either dexamethasone or methylprednisolone. Currently, we evaluate the difference in mortality associated with treating COVID-19 patients with dexamethasone versus methylprednisolone. Methods: With a retrospective multicenter study, records were reviewed for the admitted patients with severe COVID-19 during the peak of the severe COVID-19 pandemic. All admitted patients on dexamethasone or methylprednisolone were included. Patients were analyzed as all populations and propensity scores matched patients. Propensity scores were calculated for several confounders by the generalized linear model, and a “greedy” near-neighbor matching algorithm was used. Continuous variables with nonnormal distribution were analyzed by Wilcoxon signed rank test. Chi-squared and Fischer exact test analyzed categorical variables. P-values were adjusted by the Bonferroni method for both data cohorts. Body mass index was in categories. Radiological findings were divided into five categories. The outcomes: mortality, the need for home oxygen therapy, recovery, and residual symptoms on discharge were analyzed by an independent two-sample test for equality of proportions (with Yates correction), and logistic regression analysis. Results: Among the 1128 reviewed records, patients on dexamethasone or methylprednisolone were 1071, and the propensity score-matched patients were 784: dexamethasone 393 and methylprednisolone 391. There was no significant difference in the characteristics of patients between the two steroids (p-value and adjusted p-value > 0.05) for most variables. PSM adjusted a few discrepant variables before analysis. The outcome of the unmatched patients demonstrated dexamethasone benefit in the need for home oxygen therapy ( 0.05). However, matched patients demonstrated significantly lower mortality associated with dexamethasone treatment (difference -2.68%, 95%CI, -1.0, -0.004, p = 0.03, and OR 1.7, p = 0.017), and no difference for the other outcomes, including the need for home oxygen therapy (p-value > 0.05). Conclusion: Dexamethasone treatment caused significantly less mortality than methylprednisolone in treating our COVID-19 patients, but no significant difference in recovery, the need for home oxygen therapy, and residual symptoms on discharge.

Optimization of the Plugging Agent Dosage for High Temperature Salt Profile Control in Heavy Oil Reservoirs

After steam discharge in heavy oil reservoirs,the distribution of temperature,pressure,and permeability in different wells becomes irregular.Flow channels can easily be produced,which affect the sweep efficiency of the oil displacement.Previous studies have shown that the salting-out plugging method can effectively block these channels in high-temperature reservoirs,improve the suction profile,and increase oil production.In the present study,the optimal dosage of the plugging agent is determined taking into account connection transmissibility and inter-well volumes.Together with the connectivity model,a water flooding simulation model is introduced.Moreover,a non-gradient stochastic disturbance algorithm is used to obtain the optimal plugging agent dosage,which provides the basis for the high-temperature salting-out plugging agent adjustment in the field.

Studies on GA_3 Spraying Dosage for eui TGMS Rice Changxuan 3S in Its Hybrid Seed Production

[Objective] Changxuan 3S was thermo-sensitive genicmale sterile（TGMS）rice selected from irradiated seeds of Peiai 64S by 350 Gy^（60）Coγ-ray.The aim of the study was to confirm GA3 spraying dosage of Changxuan 3S with eui gene in its hybrid seed production.[Method] Changxuan 3S possessing eui gene and its parent Peiai 64S were chosen as materials.Comparison studies on sensitivity to GA3 in their hybrid seed production were carried out.[Result] The suitable stage for spraying GA3 in the hybrid seed production of Changxuan 3S was at 10% of panicles headed;The optimal dosage was 90 g/hm2 with 2 split sprayings,the first spraying of 45 g/hm2 at heading of 10% panicles and the second one of 45 g/hm2 on the following day.Under the condition of spraying GA3 at the rate of 90 g/hm2,the panicle neck exsertions of Changxuan 3S was ＋1.78 cm,and exserted stigma rate and seed setting rate of Changxuan 3S were 96.87% and 36.44%,being 21.46% and 16.33% more than those of Peiai 64S,respectively.The theoretical yield of ＂Changxuan 3S/9311＂ reached 2 931.90 kg/hm2,which was increased by 1 259.40 kg/hm2 comparing with ＂Peiai 64S/9311＂.[Conclusion] Compared with Peiai 64S,Changxuan 3S is more sensitive to GA3,which results in no or little using GA3 in seed production of Changxuan 3S.Moreover,Changxuan 3S showed higher yield potential than Peiai 64S.

Observation on Apoptosis of Erythroid Cells Induced by Dexamethasone

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.

Dexamethasone inhibits hypoxia-induced epithelial-mesenchymal transition in colon cancer

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.

Tissue microarrays in pathological examination of apoptotic acinar cells induced by dexamethasone in the pancreas of rats with severe acute pancreatitis

BACKGROUND: The good therapeutic effects of large dose of dexamethasone on severe acute pancreatitis (SAP) patients have been proved. This study was designed to investigate the influence of dexamethasone on apoptosis of acinar cells in the pancreas of rats with SAP and the protein expression of the apoptosis-regulating genes Bax and Bcl-2. METHODS: Ninety Sprague-Dawley rats with SAP were randomly divided into a model group and a dexamethasone treated group (45 rats in each group), and another 45 rats formed the sham operation group. Survival rates were calculated and gross pathological changes in the pancreas of each group were observed under a light microscope 3, 6 and 12 hours after operation. Tissue microarray technology was applied to prepare pancreatic tissue sections. The changes in Bax and Bcl-2 protein expression levels of pancreatic tissues from each group were assessed by immunohistochemical staining, and TUNEL staining was used to evaluate changes in apoptosis index. RESULTS: The model and treated groups did not differ in mortality at each time point. The pathological score for the pancreas in the treated group was significantly lower than that in the model group at 3 and 6 hours. The positive rates of Bax protein expression in the head and tail of the pancreas in the treated group at all time points were all markedly higher than those of the model group. The positive rate of Bcl-2 protein expression in the head of the pancreas in the treated group was significantly higher than that of the model group at 3 hours. TUNEL staining showed that the pancreas head and tail apoptosis indices of the treated group were markedly higher than those of the model group after 6 hours. CONCLUSIONS: Apoptosis may be a protective response. to pancreatic cell injury. The mechanism of action of dexamethasone in treating SAP may be related to the apoptosis of acinar cells in the pancreas induced by apoptosis-regulating genes such as Bax and Bcl-2. The advantages of tissue microarrays in pathological examination of the pancreas include saving of time and energy, efficiency and highly representative.

Effect of Dexamethasone and Aquaporin-1 Antisense Oligonucleotides on the Aquaporin-1 Expression in Cultured Human Trabecular Meshwork Cells

The changes in the expression of aquaporin-1 （AQP1） mRNA and protein in cultured human trabecular meshwork （HTM） cells treated with dexamethasone and transfected with antisense oligonucleotides （AS-ODN） were studied, and the implication of AQP1 regulation in corticosteroid-glaucoma and the possibility of AS-ODN inhibiting the AQP1 expression were evaluated. The cultured HTM cells in vitro were treated with different concentrations of dexamethasone and transfected with oligonucleotides for 5 days respectively. Then, total RNA and protein of HTM cells were extracted. The changes of AQP1 mRNA and protein were demonstrated qualitatively and quantitatively by RT-PCR and Western blot. Band intensities were detected by imaging analysis. There was a parallel relationship between the results of RT-PCR and those of Western blot. The expression levels of AQP1 mRNA and protein in dexamethasone-treated groups were increased initially and decreased later as dexamethasone concentration was stepped up. In the 0.04 μg/mL and 0.4 μg/mL groups, the levels of AQP1 were higher than in control group （0 μg/mL）. In the 4 μg/ mL and 40 μg/mL groups, the AQP1 expression levels were lower than in control group. AS-ODN could down-regulate the expression of AQP1 mRNA and protein in a dose-dependent manner. At 5 μg/mL, down-regulation efficiency reached the maximum. There was no statistically significant difference in the expression of AQP1 mRNA and protein between all sense oligonucleotides groups and control group. It was suggested that dexamethasone may induce the changes of the AQP1 expression in HTM cells to be involved in the occurrence of corticosteroid-glaucoma. AS-ODN can down-regulate the AQP1 expression in HTM cells to some extent.