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Nonsteroidal anti-inflammatory drug (NSAID)-induced kidney injury is one of the most common causes of renal failure. The exact pathogenesis of NSAID induced kidney injury is not fully known and the treatment is still challenging. Artemisinin (ART) gains more attention by its potent biological activities in addition to its antimalarial effect. In our research, we evaluated the preventive and therapeutic effects of ART in Diclofenac (DIC) induced kidney injury through its effect on mitochondria and regulation of sirtuin 3 (SIRT3). Thirty adult male Sprague Dawley rats were divided into five groups: control, ART, DIC, DIC + ART prophylactic, and DIC followed + ART therapeutic groups. At the end of the study, animals were scarified and the following parameters were evaluated: serum urea and creatinine, renal malondialdehyde (MDA), superoxide dismutase (SOD) and nitrate. SIRT3 was detected by western blotting and real-time PCR. Mitochondrial related markers (PGC-1α, Drp1, and mitochondrial ATP) were detected by immunoassay. Caspase-3 and LC3 II expression in kidney tissues were demonstrated by immune-histochemical staining. The kidney specimens were stained for H&E and PAS special stain. Electron microscopy was done to detect mitochondrial morphology. ART improved renal function test, oxidative stress, SIRT3 level, mitochondrial function, LC3 II expression and decrease caspase-3. Histopathological examination confirmed ART alleviation as determined by light or electron microscopy. ART can modulate biochemical and pathological changes in DIC-induced kidney injury and can be considered a new possible therapeutic approach for DIC-induced kidney injury through its effect on SIR3 and maintenance of mitochondrial homeostasis., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the relevant guidelines and regulations. All methods employed in this study, including the handling and care of animals, were performed in strict compliance with the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications No. 85–23, revised in 1996). This study was performed in accordance the Research Ethics committee of Tanta University, Faculty of Medicine. The study protocol was reviewed and approved by the Ethics Review Committee of Tanta University (approval number 35250/2/22). Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Muscle tissue is essential for overall well-being that declines with age and different illnesses. Glucocorticoids, despite being efficient in treating inflammation, can induce muscle weakness (known as glucocorticoid-induced myopathy) by affecting protein breakdown and synthesis. Glucocorticoids have a negative impact on satellite cells, which play a role in muscle regeneration. Platelet rich plasma (PRP), containing concentrated growth factors, has a potential role in enhancing tissue repair and could be used to ameliorates combat muscle wasting caused by glucocorticoids., Aim: The purpose of this study was to identify how PRP can affect dexamethasone-induced myopathy in a rat model., Methods: Twenty-four male rats were divided into four equal groups: control, PRP, steroid (dexamethasone) treated for induction of myopathy, and steroid then treated with PRP for three weeks. Skeletal muscle contractile properties, protein content of the muscle, oxidative stress markers, histological structure, myogenin gene expression and immunohistochemical expression of Myo-D, Pax-7 and LC3 were assessed., Results: dexamethasone caused significant muscle weakness, decreased protein content, increased oxidative stress, decreased expression of myogenic genes and upregulated LC3 expression. PRP administration significantly improved muscle function, increased protein content, reduced oxidative stress, and upregulated myogenic genes. Histological results confirmed these findings. Additionally, PRP decreased autophagy marker LC3 expression and increased muscle stem cell markers MyoD and Pax7., Conclusion: These results suggested that PRP could effectively prevent and reverse dexamethasone-induced muscle atrophy by promoting muscle protein synthesis, reducing oxidative stress, decreasing autophagy, and enhancing muscle stem cell activity. This study supports the potential role of PRP as a therapeutic strategy for muscle wasting disorders., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is significantly increasing, resulting in severe distress. The approved treatment for ASD only partially improves the sympoms, but it does not entirely reverse the symptoms. Developing novel disease-modifying drugs is essential for the continuous improvement of ASD. Because of its pleiotropic effect, atorvastatin has been garnered attention for treating neuronal degeneration. The present study aimed to investigate the therapeutic effects of atorvastatin in autism and compare it with an approved autism drug (risperidone) through the impact of these drugs on TLR4/NF-κB/NOX-2 and the apoptotic pathway in a valproic acid (VPA) induced rat model of autism., Methods: On gestational day 12.5, pregnant rats received a single IP injection of VPA (500 mg/kg), for VPA induced autism, risperidone and atorvastatin groups, or saline for control normal group. At postnatal day 21, male offsprings were randomly divided into four groups (n = 6): control, VPA induced autism, risperidone, and atorvastatin. Risperidone and atorvastatin were administered from postnatal day 21 to day 51. The study evaluated autism-like behaviors using the three-chamber test, the dark light test, and the open field test at the end of the study. Biochemical analysis of TLR4, NF-κB, NOX-2, and ROS using ELISA, RT-PCR, WB, histological examination with hematoxylin and eosin and immunohistochemical study of CAS-3 were performed., Results: Male offspring of prenatal VPA-exposed female rats exhibited significant autism-like behaviors and elevated TLR4, NF-κB, NOX-2, ROS, and caspase-3 expression. Histological analysis revealed structural alterations. Both risperidone and atorvastatin effectively mitigated the behavioral, biochemical, and structural changes associated with VPA-induced rat model of autism. Notably, atorvastatin group showed a more significant improvement than risperidone group., Conclusions: The research results unequivocally demonstrated that atorvastatin can modulate VPA-induced autism by suppressing inflammation, oxidative stress, and apoptosis through TLR4/NF-κB/NOX-2 signaling pathway. Atorvastatin could be a potential treatment for ASD., (© 2024. The Author(s).)

Introduction: Administration of high doses of acetaminophen (APAP) results in liver injury. Oxidative stress and iron overload play roles in the pathogenesis of APAP-induced hepatotoxicity. The present study assessed the potential hepatoprotective effects of phytic acid (PA), a natural antioxidant and iron chelator, on APAP-induced hepatotoxicity and the possible underlying mechanism through its effects on CYP2E1 gene expression, iron homeostasis, oxidative stress, and SIRT -1 expression levels. Methods: Twenty-four adult male albino mice were used in this study. Mice were divided into four groups (six mice in each group): control, APAP-treated, PA-treated and APAP + PA-treated groups. Liver function tests, serum and liver tissue iron load were evaluated in all the study groups. Hepatic tissue homogenates were used to detect oxidative stress markers, including malondialdehyde (MDA) and reduced glutathione (GSH). Histological hepatic evaluation and immunohistochemistry of SIRT -1 were performed. Quantitative real-time PCR was used for the assessment of CYP2E1 and SIRT-1 gene expressions. APAP-induced biochemical and structural hepatic changes were reported. Results: PA administration showed beneficial effects on APAP-induced hepatotoxicity through improvements in liver functions, decreased CYP2E1 gene expression, decreased serum and liver iron load, decreased MDA, increased GSH, increased SIRT -1 expression level and improvement in hepatic architecture. Conclusion: Conclusively, PA can be considered a potential compound that can attenuate acetaminophen-induced hepatotoxicity through its role as an iron chelator and antioxidant, as well as the up-regulation of SIRT -1 and down-regulation of CYP2E1., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hassan, Abdel-Halim, El-Shenbaby, Helmy, Hammad, Habotta, El Nashar, Alghamdi, Aldahhan, Al-Khater, Almohaywi and Farrag.)

Aging represents a complex biological process associated with decline in skeletal muscle functions. Aging impairs satellite cells that serve as muscle progenitor cells. Probiotic supplementation may have many beneficial effects via various mechanisms. We examined the possible effects of probiotics in stimulating the proliferation of myogenic stellate cells in aging rats. Twenty-four male albino Sprague-Dawley rats were classified equally into four groups: adult control, old control, adult + probiotics, and old + probiotics. Probiotics (Lactobacillus LB) were administered gavage at a dose of 1 ml (1 × 10 9  CFU/ml/day) for 4 weeks. A significant increase in the relative gastrocnemius weight ratio and improvement of contractile parameters was detected in the old + probiotics group (0.6 ± 0.01) compared to the old control group (0.47 ± 0.01; P < 0.001). Probiotics significantly upregulated the activities of GSH, while NO and MDA were markedly decreased compared to control groups (P ≤ 0.001). Also, probiotics increased the mRNA and protein expressions of myogenin and CD34 (P < 0.05) as determined by real-time PCR and immunohistochemistry. Moreover, the old + probiotics group showed apparent restoration of the connective tissue spaces, reflecting the all-beneficial effects of probiotics. Our findings indicated that probiotics attenuated myopathic changes in aging rats probably through activation of the myogenic stellate cells. Probiotics improved the muscle weight, function, antioxidant activity, and myogenic transcription factors of the skeletal muscle., (© 2023. The Author(s).)

Diabetes mellitus is a common metabolic disorder. About two-thirds of diabetic patients develop diabetic cardiomyopathy (DCM), which becomes a challenging issue as it severely threatens the patient's life. Hyperglycemia and the resulting advanced glycated end products (AGE) and their receptor (RAGE)/High Mobility Group Box-1 (HMGB-1) molecular pathway are thought to be key players. Recently, artemisinin (ART) has gained more attention owing to its potent biological activities beyond its antimalarial effect. Herein, we aim to evaluate the effect of ART on DCM and the possible underlying mechanisms. Twenty-four male Sprague-Dawley rats were divided into: control, ART, type 2 diabetic and type 2 diabetic treated with ART groups. At the end of the research, the ECG was recorded, then the heart weight to body weight (HW/BW) ratio, fasting blood glucose, serum insulin and HOMA-IR were evaluated. Cardiac biomarkers (CK-MB and LDH), oxidative stress markers, IL-1β, AGE, RAGE and HMGB-1 expression were also measured. The heart specimens were stained for H&E as well as Masson's trichrome. DCM induced disturbances in all studied parameters; contrary to this, ART improved these insults. Our study concluded that ART could improve DCM through modulation of the AGE-RAGE/HMGB-1 signaling pathway, with subsequent impacts on oxidative stress, inflammation and fibrosis. ART could therefore be a promising therapy for the management of DCM., (© 2023. The Author(s).)

Parkinson's disease (PD) is the second most common neurodegenerative disease. Treatment of PD is challenging, as current treatment strategies are only symptomatic and do not stop disease development. Recent studies reported neuroprotective effects of calcitriol in PD through its antioxidant and anti-inflammatory properties. The exact pathomechanisms of PD are not yet fully understood. So, investigation of different molecular pathways is challenging. Sirtuin-1 (Sirt1) modulates multiple physiological processes, including programmed cell death, DNA repair, and inflammation. Furthermore, defective autophagy is considered a key pathomechanism in PD as it eliminates protein aggregation and dysfunctional cell organelles. The present study investigated the involvement of autophagy and Sirt1/NF-κB molecular pathway in rotenone-induced PD and explored the protective and restorative effects of calcitriol through these mechanisms. Therefore, behavioral tests were used to test the effect of calcitriol on motor disability and equilibrium. Furthermore, the histological and neuronal architecture was assessed. The expression of genes encoding neuroinflammation and autophagy markers was determined by qPCR while their protein levels were determined by Western blot analysis and immune-histochemical staining. Our results indicate that behavioral impairments and dopaminergic neuron depletion in the rotenone-induced PD model were improved by calcitriol administration. Furthermore, calcitriol attenuated rotenone-induced neuroinflammation and autophagy dysfunction in PD rats through up-regulation of Sirt1 and LC3 and down-regulation of P62 and NF-κB expression levels. Thus, calcitriol could induce a neuro-protective and restorative effect in the rotenone-induced PD model by modulating autophagy and Sirt1/NF-κB pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Magdy, Farrag, Hamed, Abdallah, El Nashar, Alghamdi, Ali and Abd El-kader.)