CoQ10 targeted hippocampal ferroptosis in a status epilepticus rat model.

Status epilepticus (SE), the most severe form of epilepsy, leads to brain damage. Uncertainty persists about the mechanisms that lead to the pathophysiology of epilepsy and the death of neurons. Overloading of intracellular iron ions has recently been identified as the cause of a newly recognized form of controlled cell death called ferroptosis. Inhibiting ferroptosis has shown promise as a treatment for epilepsy, according to recent studies. So, the current study aimed to assess the possible antiepileptic impact of CoQ10 either alone or with the standard antiepileptic drug sodium valproate (SVP) and to evaluate the targeted effect of COQ10 on hippocampal oxidative stress and ferroptosis in a SE rat model. Using a lithium-pilocarpine rat model of epilepsy, we evaluated the effect of SVP, CoQ10, or both on seizure severity, histological, and immunohistochemical of the hippocampus. Furthermore, due to the essential role of oxidative stress and lipid peroxidation in inducing ferroptosis, we evaluated malonaldehyde (MDA), reduced glutathione (GSH), glutathione peroxidase 4 (GPX4), and ferritin in tissue homogenate. Our work illustrated that ferroptosis occurs in murine models of lithium-pilocarpine-induced seizures (epileptic group). Nissl staining revealed significant neurodegeneration. A significant increase in the number of astrocytes stained with an astrocyte-specific marker was observed in the hippocampus. Effective seizure relief can be achieved in the seizure model by administering CoQ10 alone compared to SVP. This was accomplished by lowering ferritin levels and increasing GPX4, reducing MDA, and increasing GSH in the hippocampus tissue homogenate. In addition, the benefits of SVP therapy for regulating iron stores, GPX4, and oxidative stress markers were amplified by incorporating CoQ10 as compared to SVP alone. It was concluded that CoQ10 alone has a more beneficial effect than SVP alone in restoring histological structures and has a targeted effect on hippocampal oxidative stress and ferroptosis. In addition, COQ10 could be useful as an adjuvant to SVP in protecting against oxidative damage and ferroptosis-related damage that result from epileptic seizures.

Potential impact of epicardial fat thickness, pentraxin-3, and high-sensitive C-reactive protein on the risk of non-proliferative diabetic retinopathy.

Purpose: We tried to clarify the potential association between systemic inflammatory markers like high-sensitive C-reactive protein (Hs-CRP), pentraxin-3 (PTX3), and epicardial fat thickness (EFT) with the non-proliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes mellitus (T2D). Previous studies dealt with diabetic retinopathy as a whole entity rather than early stages of diabetic retinopathy. Early detection of various determinants of NPDR is prioritized in clinical practice. Methods: A case-control study was conducted at Mansoura University Hospital, included 207 Egyptian subjects divided into 3 groups; 69 diabetic patients without retinopathy, 69 diabetic patients with NPDR, and 69 healthy control subjects. Participants were subjected to clinical history taking, physical examination, and laboratory assessment of Hs-CRP and plasma PTX3. Transthoracic echocardiography was applied to estimate EFT. Results: Hs-CRP, PTX3, and EFT were significantly higher in patients with T2D without retinopathy than control cohort (p = 0.033, p < 0.00 and p < 0.00, respectively). Moreover, patients with NPDR showed significantly higher values of Hs-CRP, PTX3, and EFT than diabetic comparators without retinopathy (p = 0.002, p = 0.012, and p < 0.001, respectively). Although, NPDR was positively correlated with Hs-CRP, PTX3, and EFT (p < 0.001), Hs-CRP was not an independent determinant of NPDR meanwhile, EFT (OR = 1.094, 95%CI: 1.036-1.154, P = 0.001) and PTX3 (OR = 16.145, 95%CI: 1.676-155.551, P = 0.016) were. Conclusion: Plasma pentraxin-3 and epicardial fat thickness showed more significant association with NPDR than high-sensitive C-reactive protein in patients with type 2 diabetes mellitus.

Therapeutic effect of adipose-derived mesenchymal stem cells (AD-MSCs) compared to pirfenidone on corticosteroid resistance in a mouse model of acute exacerbation of idiopathic pulmonary fibrosis.

INTRODUCTION: Acute exacerbation-idiopathic pulmonary fibrosis (AE-IPF) is a life-threatening condition. In the treatment of AE-IPF, corticosteroid medication is commonly utilized. However, there is insufficient evidence to justify its usage. Pirfenidone (PFD) has recently been discovered to be effective in the treatment of AE-IPF patients. However, regenerative therapy, such as stem cell therapy or tissue engineering, is necessary due to ineffective and limited therapies. Combining MSC transplantation with pharmacological therapy may also give additional benefits; nevertheless, its use must be proven experimentally. As a result, the goal of this study was to assess the therapeutic effects of adipose-derived mesenchymal stem cells (AD-MSCs) on corticosteroid resistance in an animal model of AE-IPF caused by bleomycin compared to PFD. MATERIALS AND METHODS: Seventy C57BL/6J male mice were randomly divided into seven groups, control, BLM, methylprednisolone (MP), PFD, AD-MSCs, PFD +MP, and AD-MSCs +MP. RESULTS: In terms of survival, collagen deposition, the acute lung injury score (ALI), and the Ashcroft score, AD-MSCs exceeded PFD. AD-MSCs + MP provided protection and preserved the lung's architecture in BLM-induced AE. In addition, AD-MSCs successfully decreased chemokine (CC motif) ligand-2 (CCL2) positive cells and lower pro-fibrotic and pro-inflammatory cytokines. CONCLUSIONS: AD-MSCs enhanced histological structure, Ashcroft and ALI scores, lung collagen deposition, survival, and cytokines in an animal model of AE-IPF. As a result, we believe that AD-MSCs may be more therapeutically helpful for AE-IPF than presently available therapies, either alone or in conjunction with MP.

Therapeutic Potential of Bone Marrow-Derived Mesenchymal Stem Cells on Experimental Liver Injury Induced by Schistosoma mansoni: A Histological Study.

BACKGROUND AND OBJECTIVES: Bone marrow derived mesenchymal stem cells (BM-MSCs) have been proposed as effective treatment of many diseases owing to their unique ability to differentiate into other cell types in vivo. Schistosoma mansoni (S. mansoni) infection is characterized by hepatic granuloma formation around schistosome eggs at acute stage of infection, followed by hepatic fibrosis at chronic and advanced stages. Whether BM-MSCs have an ameliorative effect on hepatic tissue injury caused by S. mansoni infection or not, was inspected in the current study. MATERIALS AND RESULTS: Female Swiss Albino mice were divided into a control group and an experimental group. Half of control animals served as donors for bone marrow stem cells, and the other half was used to collect liver samples. Experimental group was injected with circariae of S. mansoni, and then subdivided into three subgroups; Subgroup B1, sacrificed after eight weeks of infection without treatment, subgroup B2, received BM-MSCs at the eighth week and sacrificed four weeks later, and subgroup B3, was untreated till the twelfth week of infection. Histological examination of liver samples showed the formation of granulomas and liver fibrosis which were extensive in subgroup B3. However, treated subgroup illustrated improvement of liver histology, signs of hepatocytes regeneration, and possible contribution of oval cell in the process of hepatic and biliary regeneration. CONCLUSION: BM-MSCs decreased liver fibrosis and contributed to an increase in oval cells, generation of new hepatocytes and/or to the improvement of resident hepatocytes in S. mansoni infected mice.