Methylprednisolone Research Articles

Potential therapeutic and ameliorative effects of ramipril alone and in combination with methylprednisolone for the cytokine releasing syndrome in mice: An in vivo study.

Cytokine-releasing syndrome (CRS) is a special form of systemic inflammatory response syndrome provoked by factors like viral infections and certain immunomodulatory drugs like monoclonal antibodies and adoptive T therapy. To elucidate the potential role of ramipril (RM) and its combination with methylprednisolone (MP) against the development and progression of CRS in mice. This experiment consists of two parts: protective and therapeutic interventions. The protective experiment: in the induction group, mice received an intraperitoneal injection (IP) of 5mg/kg lipopolysaccharide (LPS) without intervention. The other groups received various drugs before the induction by three days, then observed for an additional two days (50 mg/kg MP, 3 mg/kg RM, and a combination of 1.5 mg/kg RM with 25 mg/kg MP). The second part of the study involves the therapeutic potential; all groups received similar doses of drugs in the prevention groups, except LPS induction was given first, and after one hour, the mice received daily doses of the drugs for five days. At the end of the experiment, blood and tissue samples were obtained. Mice treated with RM and its combination with MP showed improved serum TNF-α, IL-6, IL-8, IL-1β, INF-γ, MDA, and GSH in both prevention and therapeutic groups. Histopathologically, mice treated with ramipril and its combination with MP ameliorate the tissue damage in both lung and liver tissues following LPS induction. Ramipril showed protective and therapeutic effects in LPS-induced cytokine storms in mice through anti-inflammatory and antioxidant mechanisms.

Lipid-Polymer Hybrid Nanoparticles in Microparticle-Based Powder: Evaluating the Potential of Methylprednisolone Delivery for Future Lung Disease Treatment via Inhalation.

Lipid-polymer hybrid nanoparticles (LPHNPs) offer a promising method for delivering methylprednisolone (MePD) to treat lung inflammation, addressing aggregation issues seen with polymer-only formulations. This study aimed to develop LPHNPs for MePD delivery, assessing their physicochemical properties, drug loading, cytocompatibility, and release profiles, ultimately enabling inhalable microparticle-based powder. The nanoparticles were formulated using α,β-poly(N-2-hydroxyethyl)-DL-aspartamide-g-Rhodamine B-g-poly(lactic acid) (PHEA-g-RhB-g-PLA) and phospholipids DPPC, DOTAP, and DSPE-PEG2000 in a 45:30:25 weight ratio. Their size, redispersion after freeze-drying, drug loading (DL%), and controlled release were evaluated. Cytocompatibility was assessed on 16-HBE cell lines, measuring anti-inflammatory effects via IL-6 and IL-8 levels. Spray drying was optimized to produce microparticles using mannitol (MAN), leucine (LEU), and N-acetylcysteine (NAC). The nanoparticles had a size of 186 nm and a DL% of 2.9% for MePD. They showed good cytocompatibility, significantly reducing IL-6 and IL-8 levels. Spray drying yielded microparticles with a fine particle fraction (FPF) of 62.3% and a mass median aerodynamic diameter (MMAD) of 3.9 µm. Inclusion of LPHNPs@MePD (0.25% w/v) resulted in FPF and MMAD values of 56.7% and 4.4 µm. In conclusion, this study described the production of novel inhalable powders as carriers for MePD-loaded nanostructures with favorable physicochemical properties, cytocompatibility, and promising aerosol performance, indicating their potential as an effective inhalable therapy for lung inflammation with corticosteroids, especially for treating chronic diseases.

Novel therapeutic effects of rifaximin in combination with methylprednisolone for LPS-induced ‎oxidative stress and inflammation in mice‎: ‎An in vivo study

Cytokine-releasing syndrome (CRS) is a special form of ‎‎systemic inflammatory response syndrome provoked by ‎factors ‎like viral infections and certain immunomodulatory drugs.‎ To elucidate the potential ‎role of rifaximin (RIF) and its combination with methylprednisolone (MP) against the development and ‎progression of CRS in ‎mice.‎ This experiment consists of two parts: protective and therapeutic interventions. The protective experiment: in the induction group, mice received an intraperitoneal injection (IP) of 5 mg/kg lipopolysaccharide (LPS) without intervention. The other group received various drugs before the induction by three days, then observed for an additional two days (50 mg/kg MP, 50 mg/kg RIF, and a combination of 25 mg/kg RIF with 25 mg/kg MP. The second part of the study involves the therapeutic potential; all groups received similar doses of drugs to that received in the prevention groups, except LPS induction was given first, and after one hour, the mice received daily doses of the drugs for five days. At the end of the experiment, blood and tissue samples were obtained. Mice treated with RIF and its combination with MP showed improved serum TNF-α, IL-6, IL-8, IL-1β, INF-γ, MDA, and GSH in both prevention and therapeutic groups. Histopathologically, mice treated with rifaximin and its combination with MP ameliorates the tissue damage in both lung and liver tissues following LPS induction. In conclusion, rifaximin showed protective and therapeutic effects in LPS-induced cytokine storms in mice through anti-inflammatory and antioxidant mechanisms, and its combination with methylprednisolone showed additive/ synergistic action.

Inhibition of sympathetic tone via hypothalamic descending pathway propagates glucocorticoid-induced endothelial impairment and osteonecrosis of the femoral head

Osteonecrosis of the femoral head (ONFH) is a common complication of glucocorticoid (GC) therapy. Recent advances demonstrate that sympathetic nerves regulate bone homeostasis, and GCs lower the sympathetic tone. Here, we show that the dramatically decreased sympathetic tone is closely associated with the pathogenesis of GC-induced ONFH. GCs activate the glucocorticoid receptor (GR) but hinder the activation of the mineralocorticoid receptor (MR) on neurons in the hypothalamic paraventricular nucleus (PVN). This disrupts the balance of corticosteroid receptors (GR/MR) and subsequently reduces the sympathetic outflow in the PVN. Vascular endothelial cells rapidly react to inhibition of sympathetic tone by provoking endothelial apoptosis in adult male mice treated with methylprednisolone (MPS) daily for 3 days, and we find substantially reduced H-type vessels in the femoral heads of MPS-treated ONFH mice. Importantly, treatment with a GR inhibitor (RU486) in the PVN promotes the activation of MR and rebalances the ratio of GR and MR, thus effectively boosting sympathetic outflow, as shown by an increase in tyrosine hydroxylase expression in both the PVN and the sympathetic postganglionic neurons and an increase in norepinephrine levels in both the serum and bone marrow of the femoral head of MPS-treated mice. Rebalancing the corticosteroid receptors mitigates GC-induced endothelial impairment and ONFH and promotes angiogenesis coupled with osteogenesis in the femoral head, while these effects are abolished by chemical sympathectomy with 6-OHDA or adrenergic receptor-β2 (Adrb2) knockout. Furthermore, activating Adrb2 signaling in vivo is sufficient to rescue the GC-induced ONFH phenotype. Mechanistically, norepinephrine increases the expression of the key glycolytic gene 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) via Adrb2-cyclic AMP response element-binding protein (CREB) signaling. Endothelial-specific overexpression of PFKFB3 attenuates endothelial impairment and prevents severe osteonecrosis in MPS-treated Adrb2 knockout mice. Thus, GC inhibits sympathetic tone via the hypothalamic descending pathway, which, in turn, acts as a mediator of GC-induced ONFH.

Intramuscular methylprednisolone in hand osteoarthritis: a retrospective cohort study

Abstract Objectives To explore patient characteristics associated with response to intramuscular methylprednisolone (MP) therapy in hand osteoarthritis (OA). Methods We performed an exploratory monocentric retrospective study. Patients with a clinical diagnosis of hand OA who visited our outpatient clinic between July 2016 and June 2021, and received at least once an intramuscular MP injection, were included. Clinical data, including laboratory and radiologic results, were retrieved from electronic patient records (EPRs). Patients’ reported response to MP and its duration in the first six months after injection was based on free text from the EPRs. Response was categorized into three groups: no response or worsening of symptoms, modest response, and good response. Duration of response was categorized as short-term (<2 weeks), or long-term (≥2 weeks). Multivariable logistic regression models were performed to determine factors associated with good response to therapy with methylprednisolone. Results Data from 262 hand OA patients (76% female) were analyzed. A good response was experienced by 150 patients (57.2%). Among those with modest to good response, the perceived response of 162 patients (80.6%) lasted 2 weeks or longer. Univariate regression analysis indicated that the level of CRP was associated with good response (odds ratio(OR) 1.08; 95% CI 1.00 to 1.17). However, multivariate regression analysis showed no statistical significant associations. Conclusion In this retrospective study, more than half of hand OA patients displayed good response to intramuscular MP administration. The possible relation between the presence of low-grade inflammation and the response to this therapy warrants further investigation.

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.

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.

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

Intravenous Anakinra for Treating Macrophage Activation Syndrome in Adult-Onset Still's Disease.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disease characterized by fever, rash, arthritis, and multi-organ involvement. Macrophage activation syndrome (MAS), a serious complication of AOSD, poses significant diagnostic and therapeutic challenges. A 32-year-old male was diagnosed with AOSD in 2020 after being hospitalized for a fever of unknown origin and elevated liver enzymes. The patient was initially treated with corticosteroids and methotrexate but subsequently discontinued both treatment and follow-up. In September 2023, he presented with fever, sore throat, and elevated inflammatory markers. After screening for infections, methylprednisolone (MP) treatment was initiated because of AOSD activation. The following day, the patient was admitted to the intensive care unit due to an altered state of consciousness. Brain magnetic resonance imaging revealed brainstem involvement. Empirical treatments were initiated, including intravenous MP, and immunoglobulin therapy. Due to suspected macrophage activation syndrome (MAS), anakinra (ANA) infusion was initiated. Significant improvement was observed after the ANA infusion. This case highlights the complex management of severe AOSD complications, emphasizing the role of early recognition, aggressive therapy, and multidisciplinary care in improving outcomes. Macrophage activation syndrome (MAS) is a serious complication of adult-onset Still's disease characterized by systemic inflammation. Early recognition and prompt initiation of treatment are crucial due to the high mortality rate associated with MAS, especially when neurologic symptoms are present.Clinicians should not delay treatment pending confirmatory diagnostic tests when MAS is suspected, as early intervention can significantly impact patient outcomes.Anakinra, an interleukin-1 inhibitor, is typically administered subcutaneously but has shown promise when administered intravenously, particularly in severe cases of MAS.

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.

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.