Methylprednisolone Research Articles

USP13 Overexpression in BMSCs Enhances Anti-Apoptotic Ability and Guards Against Methylprednisolone-Induced Osteonecrosis in Rats.

Methylprednisolone (MPS) use is linked to increased cases of osteonecrosis of the femoral head (ONFH). Bone marrow mesenchymal stem cells (BMSCs) have shown potential for treating MPS-induced ONFH, but their effectiveness is limited by high apoptosis rates post-transplantation. We developed a pre-treatment strategy for BMSCs to improve their viability. In a rat model of MPS-induced ONFH, we evaluated the effects of USP13 overexpression in BMSCs through micro-CT, HE staining, and TUNEL staining. USP13-overexpressing BMSCs significantly reduced ONFH severity compared to plain BMSCs and direct lentivirus injection. USP13 also protected BMSCs from MPS-induced apoptosis by modulating PTEN and reducing AKT phosphorylation. This led to decreased expression of apoptotic genes and proteins in USP13-overexpressing BMSCs. Our findings highlight USP13 as a promising target for enhancing BMSC survival and efficacy in treating MPS-induced ONFH.

Inflammation-Targeted Biomimetic Nano-Decoys via Inhibiting the Infiltration of Immune Cells and Effectively Delivering Glucocorticoids for Enhanced Multiple Sclerosis Treatment.

Excessive infiltration of neutrophil and inflammatory cytokines accumulation as well as the inadequate delivery of drugs to the targeted site are key pathological cascades in multiple sclerosis (MS). Herein, inflammation-targeting biomimetic nano-decoys (TFMN) is developed that inhibit the infiltration of immune cells and effectively deliver glucocorticoids to lesions for enhanced MS treatment. Nano-decoys encapsulated with the glucocorticoid methylprednisolone (MPS) are prepared by coating neutrophil membrane (NM) on nanoparticles formed by the self-assembly of tannic acid and poloxamer188/pluronic68. Benefiting from the natural inflammation-targeting ability of activated neutrophil membranes, TFMN can target the lesion site and prevent neutrophils infiltration by adsorbing and neutralizing elevated neutrophil-related cytokines, subsequently modulating the inflammatory microenvironment in experimental autoimmune encephalomyelitis mice. TFMN exhibits a strong antioxidant capacity and scavenged excessive reactive oxygen species to enhance neuronal protection. Furthermore, at the inflammation site, perforin, discharged by cytotoxic T-lymphocytes, triggered the controlled release of MPS within the TFMN through perforin-formed pores in the NM. Simultaneously, this mechanism protected neurons from perforin-induced toxicity. The MPS liberated at the targeted site achieves optimal drug accumulation, thereby enhancing therapeutic efficacy. In conclusion, the innovative system shows potential for integrating various therapeutic agents, offering a novel strategy for CNS disorders.

Effectiveness of Insolubilized Poly(vinyl alcohol)-Based Electrospun Fiber-Loaded Methylprednisolone by Enzyme-Catalyzed Cross-Linking in a Rat Spinal Cord Injury Model.

Spinal cord injury (SCI) has been implicated in neural loss and, consequently, motor/sensory impairment. Here, we propose an improved formation for fibrous mat fabrication from the derivatives of poly(vinyl alcohol) (PVA) and gelatin (Gela) through horseradish peroxidase-mediated cross-linking, providing a sustained release of methylprednisolone (MP) for SCI repair. After 28 days, the animals were evaluated in terms of remyelination and apoptosis and underwent behavioral tests. The mechanical properties, hydrophobicity, and degradation rate of PVAPh/GelaPh fibrous mats were significantly improved as compared with those of PVAPh samples. This could provide the desired structure for a sustained MP release. The seeded cells could adhere and proliferate to the composite fibers, which indicates the cytocompatibility of the resultant PVAPh/GelaPh fibrous mat. The results showed significant reductions in the number of apoptotic neurons and a substantial improvement in remyelination in the SCI+ PVAPh/GelaPh + MP group. The behavioral tests confirmed improvement in locomotor hindlimb function following treatment. The MP-loaded PVAPh/GelaPh mat developed through the long-term release of MP and the biocompatible fabricated mat could inhibit axonal demyelination, attenuate apoptosis, and improve the functional outcome, which verified the potential of PVAPh/GelaPh + MP nanocomposites as a bioactive scaffold for SCI regeneration.

Kawasaki Disease: A Single-Center Study from a Tertiary Care hospital in Dhaka, Bangladesh

Background: Kawasaki Disease (KD) is recognized as the leading cause of acquired heart disease in children in developed countries. This is a pioneer study from Bangabandhu Sheikh Mujib Medical University (BSMMU), documenting the common epidemiological, clinical, laboratory and echocardiographic findings, including management and immediate outcome of KD children. Method: This retrospective study includes all patients with a diagnosis of KD, who attended the pediatric rheumatology division at BSMMU from January 2015 to December 2019. Data were collected from medical records at diagnosis and immediately after management. Relevant statistical tests were done and a p value < 0.05 was considered as statistically significant. Result: A total of 129 cases were diagnosed with KD, among them complete KD cases were 62% and incomplete KD was 38%. The mean age at onset was significantly higher in incomplete KD than complete KD. The majority of the cases (67%) were between 1 to 5 years of age and male (72%) children were predominant. Fever was the most common presenting feature (100%), followed by bilateral conjunctivitis, mucosal involvement, rash, changes in extremities, cervical lymphadenopathy and others. Coronary artery dilatation was present in 30.5% cases with no significant differences between complete and incomplete KD cases. Aspirin was given to all the cases and IVIG was given to only 46.6% children. Rests of the children were treated with methyl prednisolone. All the cases improved after treatment and there was no immediate mortality. Conclusion: It seems that KD is not an uncommon disease and incomplete KD cases are relatively more prevalent. About 30% KD cases had coronary artery abnormalities. Immediate outcome of management is excellent but needs long term follow-up. BANGLADESH J CHILD HEALTH 2023; VOL 47 (1) : 9-16

Clickable immune-microenvironment modulated hydrogels for spinal cord injury repair

Spinal cord injury (SCI) is a devastating condition without effective therapy currently available. The inflammatory cascade following SCI leads to neuronal apoptosis and glial cell activation. The utilization of local injectable hydrogels with immunotherapy drugs directly into injured nerve tissues represents a promising therapeutic strategy. Herein, injectable hydrogels grafted with clickable methylprednisolone (MP) and cellular adhesion peptide were developed using free radical polymerization for promoting nerve regeneration following SCI. MP conjugated hydrogels could modulate the immunoinflammatory microenvironment of SCI and sustain neuron survival. The multi-stiffness hydrogels were fabricated by adjusting concentration ratios to evaluate appropriate mechanical stimuli. In a model of dorsal root ganglion, MP grafted hydrogels with mechanical signals similar to those of adult rat spinal cords demonstrated superior efficacy in promoting dorsal root ganglion growth. MP grafted hydrogels could regulate the immune-inflammatory microenvironment, promote recovery of both motor function and sensory functions. The positive findings suggested that the interplay between immunomodulation and mechanical signals plays a crucial role in promoting nerve regeneration, indicating significant potential for hydrogels as a therapeutic approach for repairing SCI.

The Effects of Different Treatment Methods on Blood Hematological Parameters İn COVID 19: A Retrospective Look at Patients in Pandemic İntensive Care Unit During The First Wave of the Pandemic

Introduction: In this study, we compared the pre- and post-treatment values of basic hematological parameters in severe COVID 19 patients, whose were received favipiravir, tocilizumab, methylprednisolone and convalescent plasma therapy. Methods: Hematological parameters such as eosinophyl, neutrophil, lymphocyte, platelet count and, neutrophil / lymphocyte, platelet/ lymphocyte ratio were investigated pre and post treatment of favipiravir, tocilizumab convalescent plasma and methylprednisolone in severe COVID 19 patients in ICU. Results: Lymphocyt values were increased after convelescent plasma theraphy and i.v. methyl prednisolon group. Eosinophil count improvement was only in the favipiravir group . We found that favipiravir, convalescent plasma andmethyl prednisolon treatment, were statistically significant increased both NLR and PLR. Conclusion : Hematologic parameters and their contribution of the respond of the treatment and clinical improvement should be taken into account.

An oil-in-gel type of organohydrogel loaded with methylprednisolone for the treatment of secondary injuries following spinal cord traumas

The secondary injuries following traumatic spinal cord injury (SCI) is a multiphasic and complex process that is difficult to treat. Although methylprednisolone (MP) is the only available pharmacological regime for SCI treatment, its efficacy remains controversial due to its very narrow therapeutic time window and safety concerns associated with high dosage. In this study, we have developed an oil-in-gel type of organohydrogel (OHG) in which the binary oleic-water phases coexist, for the local delivery of MP. This new OHG is fabricated by a glycol chitosan/oxidized hyaluronic acid hydrophilic network that is uniformly embedded with a biocompatible oil phase, and it can be effectively loaded with MP or other hydrophobic compounds. In addition to spatiotemporally control MP release, this biodegradable OHG also provides a brain tissue-mimicking scaffold that can promote tissue regeneration. OHG remarkably decreases the therapeutic dose of MP in animals and extends its treatment course over 21 d, thereby timely manipulating microglia/macrophages and their associated with signaling molecules to restore immune homeostasis, leading to a long-term functional improvement in a complete transection SCI rat model. Thus, this OHG represents a new type of gel for clinical treatment of secondary injuries in SCI.

Administration of methylprednisolone do not affect the spinal scar component of spinal cord injury

Objective The aim of this study is to evaluate the impact of methylprednisolone (MP) on scar composition following spinal cord injury (SCI). Design A total of 40 adult Sprague Dawley rats underwent right hemisection injuries to the spinal cord. Interventions The rats were randomly divided into two groups: the vehicle group and the MP group. In the MP group, rats received intraperitoneal injections of MP at a dose of 30 mg/kg for 7 consecutive days, while the vehicle group received intraperitoneal injections of saline as a control. Weekly assessments of hindlimb performance in the rat models were conducted using the Basso–Beattie–Bresnahan test (BBB) score and the horizontal ladder-walking test. Changes in scar components were identified through immunofluorescence staining, and an axonal regeneration assay was employed to evaluate regrowth under inhibitory conditions. Results The administration of MP led to a significant improvement in BBB scores compared to the control group at 7 days post-injury, although this improvement was not consistent. Furthermore, rats in the MP group did not demonstrate progressive improvement in horizontal ladder walking. Notably, there were no significant changes in the content of scar components in the injured area following MP treatment, and the axon length of neurons treated with MP did not exhibit significant extension compared to the vehicle group. Conclusions Our findings indicate that the administration of MP does not effectively enhance hindlimb motor function or promote neuronal axon growth within a scarred environment after SCI.

Sex-Specific Associations between Thyroid Status, Inflammation and Hemostasis Biomarkers in Patients with Subacute Thyroiditis.

Background: Subacute thyroiditis (SAT) is characterized by profound inflammation and fluctuations in thyroid hormones which may affect the hemostasis balance. This study investigates sex-specific associations between thyroid status, inflammation and hemostasis biomarkers in SAT. Methods: We included 52 patients (40 women and 12 men) treated with non-steroidal anti-inflammatory drugs (NSAID) or methylprednisolone (MPS). Free thyroxine (fT4), thyroid stimulating hormone, C-reactive protein, complete blood count and routine hemostasis parameters were assessed. Results: Both men and women were in hyperthyroid state and had comparable levels of inflammatory biomarkers. A shortened activated partial thromboplastin time (aPTT) was observed in 16.7% of the men and 10% of the women (p = 0.562), and a shortened prothrombin time (PT) was observed in 33% of the men and 12.5% of the women (p = 0.094). In men, aPTT positively correlated with fT4 (r = 0.627; p < 0.05), while PT positively correlated with leukocyte-based inflammatory indices in women (p < 0.05). NSAID-treated patients had lower aPTTs and platelet counts than those treated with MPS (p < 0.05). Principal component analysis extracted "proinflammatory", "prothrombotic" and "antithrombotic" factors, but the "proinflammatory" factor was the independent predictor of elevated fT4 in women (OR = 2.705; p = 0.036). Conclusions: Our data demonstrated sex-specific associations of thyroid status and inflammatory biomarkers with hemostasis parameters in SAT. Routine hemostasis screening tests may help in monitoring the changes in the hemostasis system over the course of SAT.

Natural Polyphenol Delivered Methylprednisolone Achieve Targeted Enrichment for Acute Spinal Cord Injury Therapy.

The strong anti-inflammatory effect of methylprednisolone (MP) is a necessary treatment for various severe cases including acute spinal cord injury (SCI). However, concerns have been raised regarding adverse effects from MP, which also severely limits its clinical application. Natural polyphenols, due to their rich phenolic hydroxyl chemical properties, can form dynamic structures without additional modification, achieving targeted enrichment and drug release at the disease lesion, making them a highly promising carrier. Considering the clinical application challenges of MP, a natural polyphenolic platform is employed for targeted and efficient delivery of MP, reducing its systemic side effects. Both in vitro and SCI models demonstrated polyphenols have multiple advantages as carriers for delivering MP: (1) Achieved maximum enrichment at the injured site in 2 h post-administration, which met the desires of early treatment for diseases; (2) Traceless release of MP; (3) Reducing its side effects; (4) Endowed treatment system with new antioxidative properties, which is also an aspect that needs to be addressed for diseases treatment. This study highlighted a promising prospect of the robust delivery system based on natural polyphenols can successfully overcome the barrier of MP treatment, providing the possibility for its widespread clinical application.

Inhibition of insulin degrading enzyme suppresses osteoclast hyperactivity via enhancing Nrf2-dependent antioxidant response in glucocorticoid-induced osteonecrosis of the femoral head

BackgroundOsteoclast hyperactivation due to the pathological overproduction of reactive oxygen species (ROS) stimulated by glucocorticoids (GCs) is one of the key drivers behind glucocorticoid-induced osteonecrosis of the femoral head (GIONFH). The insulin degrading enzyme (IDE), a conserved Zn2+ metallo-endopeptidase, facilitates the DNA binding of glucocorticoid receptor and plays a substantial role in steroid hormone-related signaling pathways. However, the potential role of IDE in the pathogenesis of GIONFH is yet undefined.MethodsIn this study, we employed network pharmacology and bioinformatics analysis to explore the impact of IDE inhibition on GIONFH with 6bK as an inhibitory agent. Further evidence was collected through in vitro osteoclastogenesis experiments and in vivo evaluations involving methylprednisolone (MPS)-induced GIONFH mouse model.ResultsEnrichment analysis indicated a potential role of 6bK in redox regulation amid GIONFH development. In vitro findings revealed that 6bK could attenuate GCs-stimulated overactivation of osteoclast differentiation by interfering with the transcription and expression of key osteoclastic genes (Traf6, Nfatc1, and Ctsk). The use of an H2DCFDA probe and subsequent WB assays introduced the inhibitory effects of 6bK on osteoclastogenesis, linked with the activation of the nuclear factor erythroid-derived 2-like 2 (Nrf2)-mediated antioxidant system. Furthermore, Micro-CT scans validated that 6bK could alleviate GIONFH in MPS-induced mouse models.ConclusionsOur findings suggest that 6bK suppresses osteoclast hyperactivity in GCs-rich environment. This is achieved by reducing the accumulation of intracellular ROS via promoting the Nrf2-mediated antioxidant system, thus implying that IDE could be a promising therapeutic target for GIONFH.

Nodular posterior scleritis mimicking melanotic choroidal melanoma: A diagnostic dilemma.

To report a case of atypical nodular posterior scleritis mimicking as a melanotic choroidal melanoma. Descriptive case report. A 38-year-old female presented with sudden onset diminution of vision, severe pain and redness in her right eye. She was diagnosed to have choroidal melanoma in her left eye one year ago and underwent enucleation. On examination, conjunctiva was injected in right eye with cells in anterior vitreous face (AVF). Fundus examination revealed a large pigmented choroidal mass temporal to macula with exudative retinal detachment. Systemic evaluation and multimodal imaging ruled out the possibility of a choroidal melanoma or metastasis, with a presumptive diagnosis of nodular posterior scleritis. Three cycles of intravenous methyl prednisolone (IVMP) with a tapering dose of oral corticosteroids showed drastic improvement in symptoms with resolution of choroidal mass - further confirming the diagnosis. In cases of choroidal mass with an inflammatory component, a trial of steroids is worthwhile to prevent clinical misjudgement and devastating treatment outcomes including enucleation.

Fibroblast growth factor 23 inhibition attenuates steroid-induced osteonecrosis of the femoral head through pyroptosis

Steroid-induced osteonecrosis of the femoral head (SONFH) is the predominant cause of non-traumatic osteonecrosis of the femoral head (ONFH). Impaired blood supply and reduced osteogenic activity of the femoral head are the key pathogenic mechanisms of SONFH. Fibroblast growth factor 23 (FGF23) levels are not only a biomarker for early vascular lesions caused by abnormal mineral metabolism, but can also act directly on the peripheral vascular system, leading to vascular pathology. The aim of this study was to observe the role of FGF23 on bone microarchitecture and vascular endothelium, and to investigate activation of pyroptosis in SONFH. Lipopolysaccharide (LPS) combined with methylprednisolone (MPS) was applied for SONFH mouse models, and adenovirus was used to increase or decrease the level of FGF23. Micro-CT and histopathological staining were used to observe the structure of the femoral head, and immunohistochemical staining was used to observe the vascular density. The cells were further cultured in vitro and placed in a hypoxic environment for 12 h to simulate the microenvironment of vascular injury during SONFH. The effect of FGF23 on osteogenic differentiation was evaluated using alkaline phosphatase staining, alizarin red S staining and expression of bone formation-related proteins. Matrigel tube formation assay in vitro and immunofluorescence were used to detect the ability of FGF23 to affect endothelial cell angiogenesis. Steroids activated the pyroptosis signaling pathway, promoted the secretion of inflammatory factors in SONFH models, led to vascular endothelial dysfunction and damaged the femoral head structure. In addition, FGF23 inhibited the HUVECs angiogenesis and BMSCs osteogenic differentiation. FGF23 silencing attenuated steroid-induced osteonecrosis of the femoral head by inhibiting the pyroptosis signaling pathway, and promoting osteogenic differentiation of BMSCs and angiogenesis of HUVECs in vitro.

Methylprednisolone Modulates the Tfr/Tfh ratio in EAE-Induced Neuroinflammation through the PI3K/AKT/FoxO1 and PI3K/AKT/mTOR Signalling Pathways.

Methylprednisolone (MP) is a potent glucocorticoid that can effectively inhibit immune system inflammation and brain tissue damage in Multiple sclerosis (MS) patients. T follicular helper (Tfh) cells are a subpopulation of activated CD4 + T cells, while T follicular regulatory (Tfr) cells, a novel subset of Treg cells, possess specialized abilities to suppress the Tfh-GC response and inhibit antibody production. Dysregulation of either Tfh or Tfr cells has been implicated in the pathogenesis of MS. However, the molecular mechanism underlying the anti-inflammatory effects of MP therapy on experimental autoimmune encephalomyelitis (EAE), a representative model for MS, remains unclear. This study aimed to investigate the effects of MP treatment on EAE and elucidate the possible underlying molecular mechanisms involed. We evaluated the effects of MP on disease progression, CNS inflammatory cell infiltration and myelination, microglia and astrocyte activation, as well as Tfr/Tfh ratio and related molecules/inflammatory factors in EAE mice. Additionally, Western blotting was used to assess the expression of proteins associated with the PI3K/AKT pathway. Our findings demonstrated that MP treatment ameliorated clinical symptoms, inflammatory cell infiltration, and myelination. Furthermore, it reduced microglial and astrocytic activation. MP may increase the number of Tfr cells and the levels of cytokine TGF-β1, while reducing the number of Tfh cells and the levels of cytokine IL-21, as well as regulate the imbalanced Tfr/Tfh ratio in EAE mice. The PI3K/AKT/FoxO1 and PI3K/AKT/mTOR pathways were found to be involved in EAE development. However, MP treatment inhibited their activation. MP reduced neuroinflammation in EAE by regulating the balance between Tfr/Tfh cells via inhibition of the PI3K/AKT/FoxO1 and PI3K/AKT/mTOR signalling pathways.

Comparison between Standard Dose Methyl-Prednisolone and Mega Dose Methyl-prednisolone As Regards Outcome in SARS.COV.2 Patients in Intensive Care Unit: A Retrospective Study

Abstract Background Deadly pandemics and disease emergences are not new phenomena: they have been challenging human existence throughout recorded history. Some have killed sizeable percentages of humanity, but humans have always searched for, and often found, ways of mitigating their deadly effects. Objective to compare between standard dose methyl prednisolone (1-2 mg/kg) and mega dose methyl prednisolone (0.5 g to 1g) as regards outcome reflected by mortality rate, percentage of mechanically ventilated patients and ICU length of stay of COVID 19 patients admitted in ICU. Patients and Methods After obtaining approval from the Research Ethical Committee of Ain Shams University (FMASU MS 41/2022) this study was obtained from Ain Shams University Isolation Hospitals records. Group A: Patients admitted in ICU, COVID PCR positive and requiring oxygen therapy who received methyl prednisolone standard dose (1-2 mg/kg). Group B: Patients admitted in ICU, COVID PCR positive and requiring oxygen therapy who received methyl prednisolone mega dose (0.5-1 g per day). Results This study showed that there is no significant statistical difference between receiving standard dose and mega dose methyl prednisolone as regards mortality rate or need for mechanical ventilation. Conclusion This study showed that there is no significant statistical difference between receiving standard dose and mega dose methyl prednisolone as regards mortality rate or need for mechanical ventilation. But showed significant statistical difference as regards ICU length of stay denoting that patients received mega dose methyl prednisolone showed increased ICU stay.

Use of Corticosteroids on Prophylaxis of New-Onset Atrial Fibrillation after Cardiac Surgery

Abstract Background Most cardiac operations are performed under cardiopulmonary bypass(CPB); however, it is well known that cardiopulmonary bypass often causes systemic inflammatory response syndrome (SIRS). Cardiac tissue inflammation induced by the CPB and surgical trauma has been previously hypothesized to cause POAF. The relationship between inflammation and atrial fibrillation after cardiac surgery is further strengthened by studies that showed that corticosteroid (CS) prophylaxis can reduce the occurrence of atrial fibrillation after cardiac surgery. Aim of the Work to determine the efficacy of corticosteroids in prophylaxis of POAF and shorten length of intensive care unit (ICU) and hospital stay. Patients and Methods This is randomized controlled clinical trial on 84 patients who underwent their first elective cardiac surgery under cardiopulmonary bypass in Ain Shams University Hospitals. Patients were randomized into two equal groups (n = 42 each) as the control group who underwent a standard cardiopulmonary bypass without any additional medication which was performed under the supervision of a specialized elite and experts in their specialization, and the Methylprednisolone (MP) group who was given 1 g of methylprednisolone (divided into 250 mg every 6h once in the ICU), The primary outcome is the overall occurrence of postoperative AF during the first 72 hours after cardiac surgery. Secondary outcomes are the length of hospital stay, and intensive care unit (ICU) stay. Results This study revealed that using corticosteroids effective in reducing the incidence of POAF without increasing the incidence of postoperative complications and adverse effects due to corticosteroids therapy. This study showed decreased risk of developing AF in patients undergoing cardiac surgery. The incidence of POAF was found be significant lower in MP group 16.7% (7 patients developed AF) versus 35.7% in the control group (15 patients developed AF) (p 0.047). Conclusion Use of Corticosteroids is effective in prophylaxis of POAF in patients undergoing elective cardiac surgery in terms of reducing its incidence and decreasing the length of ICU and hospital stay.

Methylprednisolone dosing for pediatric critical asthma: a single-center cohort study

Objective: We aimed to characterize intravenous (IV) methylprednisolone (MP) dosing regimens and clinical outcomes for children hospitalized for critical asthma (CA). Methods: A single-center, retrospective review was performed of children admitted to the pediatric intensive care unit (PICU) for CA between September 2015 and October 2019. Patients 5 to 17 years old, initiated on continuous nebulized albuterol, and prescribed at least one dose of IV MP were included. The primary outcome was to characterize PICU MP dosing. Cohorts were then compared by MP dosing: conservative-dose methylprednisolone (CDMP, < 0.5 mg/kg/dose every 6 hours) and standard-dose methylprednisolone (SDMP, > 0.5 mg/kg/dose every 6 hours). Clinical efficacy endpoints were duration of continuous nebulized albuterol and PICU length of stay (LOS). Safety endpoints included corticosteroid-related adverse events. Results: Of 168 children studied, 50 (29.8%) were prescribed CDMP and 118 (70.2%) SDMP. The overall mean MP dose was 31.3 ± 19.6 mg (weight-adjusted: 0.77 ± 0.32 mg/kg/dose). Compared to those prescribed SDMP, those prescribed CDMP had a shorter median duration of continuous nebulized albuterol (12.8 [IQR: 10.5–20] versus 17.3 [IQR: 11.3–29.7] hours, p = 0.019) and median PICU LOS (0.9 [IQR: 0.7–1.4] versus 1.2 [IQR: 0.9–1.8] days, p = 0.012). No corticosteroid-related adverse events were observed. In adjusted models, weight-adjusted IV MP dose was not associated with PICU LOS or duration of continuous nebulized albuterol. Conclusions: Intravenous MP dosing for pediatric CA varied widely in our study sample. Prospective, controlled trials are required to validate our observations including clinical efficacy and safety endpoints.

Methylprednisolone alleviates lung injury in sepsis by regulating miR-151-5p/USP38 pathway

BackgroundAcute lung injury (ALI) is manifested by increased blood vessel permeability within the lungs and subsequent impairment of alveolar gas exchange. Methylprednisolone (MP) is commonly used as a treatment for ALI to reduce inflammation, yet its molecular mechanism remains unclear. This study aims to explore the underlying mechanisms of MP on ALI in a model induced by lipopolysaccharide (LPS). Material and MethodsThe proliferation, viability, apoptosis, and miR-151-5p expression of alveolar type II epithelial cells (AECII) were detected using the cell EdU assay, Annexin V/PI Apoptosis Kit, counting kit-8 (CCK-8) assay, and RT-qPCR. Western blot analysis was used to detect the Usp38 protein level. IL-6 and TNF-α were measured by ELISA. The combination of miR-151-5p and USP38 was determined by chromatin immunoprecipitation (ChIP)-PCR and dual-luciferase reporter assay. ResultsMP greatly improved pulmonary function in vivo, reduced inflammation, and promoted the proliferation of the alveolar type II epithelial cells (AECII) in vitro. By comparing the alterations of microRNAs in lung tissues between MP treatment and control groups, we found that miR-151-5p exhibited a significant increase after LPS-treated AECII, but decreased after MP treatment. Confirmed by a luciferase reporter assay, USP38, identified as a downstream target of miR-151-5p, was found to increase after MP administration. Inhibition of miR-151-5p or overexpression of USP38 in AECII significantly improved the anti-inflammatory, anti-apoptotic, and proliferation-promotive effects of MP. ConclusionIn summary, our data demonstrated that MP alleviates the inflammation and apoptosis of AECII induced by LPS, and promotes the proliferation of AECII partially via miR-151-5p suppression and subsequent USP38 activation.

C-Phycocyanin Prevents Oxidative Stress, Inflammation, and Lung Remodeling in an Ovalbumin-Induced Rat Asthma Model.

Asthma is a chronic immunological disease related to oxidative stress and chronic inflammation; both processes promote airway remodeling with collagen deposition and matrix thickening, causing pulmonary damage and lost function. This study investigates the immunomodulation of C-phycocyanin (CPC), a natural blue pigment purified from cyanobacteria, as a potential alternative treatment to prevent the remodeling process against asthma. We conducted experiments using ovalbumin (OVA) to induce asthma in Sprague Dawley rats. Animals were divided into five groups: (1) sham + vehicle, (2) sham + CPC, (3) asthma + vehicle, (4) asthma + CPC, and (5) asthma + methylprednisolone (MP). Our findings reveal that asthma promotes hypoxemia, leukocytosis, and pulmonary myeloperoxidase (MPO) activity by increasing lipid peroxidation, reactive oxygen and nitrogen species, inflammation associated with Th2 response, and airway remodeling in the lungs. CPC and MP treatment partially prevented these physiological processes with similar action on the biomarkers evaluated. In conclusion, CPC treatment enhanced the antioxidant defense system, thereby preventing oxidative stress and reducing airway inflammation by regulating pro-inflammatory and anti-inflammatory cytokines, consequently avoiding asthma-induced airway remodeling.

Hypoxia-responsive microgels act as an intra-articular lubricant and inflammatory inhibitor for osteoarthritis therapy

The reduced oxygen concentration is a distinctive feature of osteoarthritic (OA) cartilage, whereas the mechanical friction also contributes to the inflammatory hypoxia microenvironment of OA. Herein, novel hypoxia-responsive methylprednisolone (MP) delivery microgels combining the capability of reactive oxygen species (ROS)-depletion and lubrication were constructed for regulating the microenvironment of OA. Methacrylate-modified sulfonated azocalix[4] arene (MACA) loaded with MP, the copolymers consisting of bioinspired lubricant 2-methacryloxyethyl phosphorylcholine (MPC), and polyethylene glycol-modified ROS-responsive poly(thioketal) (PEG-4PTK) were crosslinked together to construct the microgels. The zwitterionic MPC offered a lubrication effect, while the ROS-elimination was contributed by the PTK segments and the phenol groups in MACA. The microgels responsively released cargos in inflammatory environment and decreased inflammation by inhibiting the production of ROS and regulating the expression of inflammatory cytokines, and showed the lowest hypoxia-inducible factor-1α (HIF-1α) positive area and presented more deposition of glycosaminoglycans and collagen II with a smoother and integrated cartilage structure in therapy of OA in rats in vivo.