Expression of Tie2 (angiopoietin receptor) on the monocyte subpopulations from ischemic stroke patients: Histological and flowcytometric studies

Introduction. Different subpopulations of monocytes play roles in phagocytosis, inflammation, and angiogenic processes e.g., Tie2-expressing monocytes (TEMs). The brain is flooded with macrophages that are derived from monocytes within 3-7 days after a stroke. This study aimed to determine the expression level of Tie2 (an angiopoietin receptor) on monocytes and their subpopulations in ischemic stroke patients using the histological and immunohistological study of bone marrow biopsies and blood flow cytometry examination. Methods. Ischemic stroke patients within two days were selected. Participants in the control group were healthy volunteers of matched age and gender. Sample collection was performed within 24 to 48 hours after medical consultants confirmed the stroke diagnosis. An iliac crest bone marrow biopsy was obtained and fixed for histological and immunohistological staining with antiCD14 and antiCD68. Flow cytometry was used to determine the total monocyte population, monocyte subpopulations, and TEMs after staining with monoclonal antibodies to CD45, CD14, CD16, and Tie2. Results. Post-stroke patients' bone marrow cells were hypercellular. There was an apparent increase in CD68 and CD14-positive cells. Ischemic stroke patients exhibited low percentages of nonclassical monocytes CD14lowCD16++, with an increase in intermediate monocytes CD14highCD16+. Moreover, ischemic stroke patients had significantly higher levels of TEMs than control group. Conclusions. The results of this study demonstrate dysregulation of angiogenesis in monocyte subsets in ischemic stroke patients, which could be used as an early diagnostic marker of neurovascular damage and may need angiogenic therapy or improved medications to prevent further damage of blood vessel

Current developments in gene therapy for amyotrophic lateral sclerosis

Introduction: Amyotrophic lateral sclerosis (ALS) is a devastating adult neurodegenerative disorder characterized by motor neuron degeneration and death around 3 years from onset. So far, riluzole is the only treatment available, although it only offers a slight increase in survival. The complex etiology of ALS, with several genes able to trigger the disease, makes its study difficult. Areas covered: RNA-mediated or protein-mediated toxic gain-of-function leading to motor neuron degeneration appears to be likely common pathogenic mechanisms in ALS. Consequently, gene therapy technologies to reduce toxic RNA and/or proteins and to protect motor neurons by modulating gene expression are at the forefront of the field. Here, we review the most promising scientific advances, paying special attention to the successful treatments tested in animal models as well as analyzing relevant gene therapy clinical trials. Expert opinion: Despite broad advances in target gene identification in ALS and advances in gene therapy technologies, a successful gene therapy for ALS continues to elude researchers. Multiple hurdles encompassing technical, biological, economical and clinical challenges must be overcome before a therapy for patients becomes available. Optimism remains due to positive results obtained in several in vivo studies demonstrating significant disease amelioration in animal models of ALS.Depto. de Bioquímica y Biología MolecularFac. de MedicinaTRUEpu

Increased Inflammatory Markers at AMPH-Addicts Are Related to Neurodegenerative Conditions: Alzheimer’s Disease

Amphetamine addiction is widespread worldwide despite causing severe physical and mental problems, including neurodegeneration. One of the most common neurodegenerative disorders is Alzheimer’s disease (AD). Several inflammatory markers have been linked to AD. Previous studies have also found these biomarkers in amphetamine-addicts (AMPH-add). This study thus seeks to understand how AD and AMPH-addiction are related. A case–control observational study was conducted. Seventeen AMPH-adds ranging in age from 23 to 40 were recruited from Al Amal Psychiatric Hospital. In addition, 19 healthy subjects matching their age and gender were also recruited. The Luminex technique was used to measure serum alpha 1 antichymotrypsin (ACT), pigment epithelium-derived factor (PEDF), and macrophage inflammatory protein-4 (MIP-4), after complying with ethical guidelines and obtaining informed consent. In addition, liver function enzymes were correlated to AD’s predictive biomarkers in AMPH-adds. AMPH-adds had significantly higher serum levels of ACT, PEDF, and MIP-4 when compared to healthy controls (p = 0.03, p = 0.001, and p = 0.012, respectively). Furthermore, there is a significant correlation between lower ALT levels and elevated AST to ALT ratios in AMPH-adds (r = 0.618, 0.651, and p = 0.0001). These changes in inflammatory biomarkers may be linked to the onset of AD at a young age in amphetamine-drug addicts

Increased Inflammatory Markers at AMPH-Addicts Are Related to Neurodegenerative Conditions: Alzheimer’s Disease

Amphetamine addiction is widespread worldwide despite causing severe physical and mental problems, including neurodegeneration. One of the most common neurodegenerative disorders is Alzheimer’s disease (AD). Several inflammatory markers have been linked to AD. Previous studies have also found these biomarkers in amphetamine-addicts (AMPH-add). This study thus seeks to understand how AD and AMPH-addiction are related. A case–control observational study was conducted. Seventeen AMPH-adds ranging in age from 23 to 40 were recruited from Al Amal Psychiatric Hospital. In addition, 19 healthy subjects matching their age and gender were also recruited. The Luminex technique was used to measure serum alpha 1 antichymotrypsin (ACT), pigment epithelium-derived factor (PEDF), and macrophage inflammatory protein-4 (MIP-4), after complying with ethical guidelines and obtaining informed consent. In addition, liver function enzymes were correlated to AD’s predictive biomarkers in AMPH-adds. AMPH-adds had significantly higher serum levels of ACT, PEDF, and MIP-4 when compared to healthy controls (p = 0.03, p = 0.001, and p = 0.012, respectively). Furthermore, there is a significant correlation between lower ALT levels and elevated AST to ALT ratios in AMPH-adds (r = 0.618, 0.651, and p = 0.0001). These changes in inflammatory biomarkers may be linked to the onset of AD at a young age in amphetamine-drug addicts

The combined effect of honey and olive oil against methotrexate mediated hepatotoxicity in rats: A biochemical, histological and immunohistological study

Background. Honey and olive oil are natural products that have high nutritional values, and therapeutic properties. Cytotoxic drugs, like methotrexate (MTX) are used to treat malignancies in tumour cells; however, these drugs also have serious side effects that could threaten the patient's life. Aim. To evaluate the potential protective effects of honey and olive oil, administered alone or together, against MTX-induced hepatotoxicity in rats. Methods. Adult male albino rats were divided: Group I: negative control (n=8); II: honey (daily by oral 1.2 g/kg bwt (n=8), III: olive oil (1 ml/day) (n=8), IV: single intraperitoneal injection of MTX (20 mg/kg bwt) (n=8), V: diluted honey for 3 days before injection of MTX (n=8), Group VI: olive oil for 3 days before injection of MTX (n=8), Group VII: both honey and olive oil for 3 days before injection of MTX (n=8). After treatment, rats were sacrified and blood samples were collected to determine liver function parameters, liver tissue used to measure the oxidative (malondialdehyde), antioxidative parameters (superoxide dismutase, catalase and glutathione peroxidase), histological and immunohistochemical techniques. Results. The administration of honey and olive oil exerted a protective effect against MTX-induced hepatotoxicity, as demonstrated by the normalization of the liver enzymes, proteins and total bilirubin and by the histopathological and immunohistological changes observed in the livers. Both agents also reversed the oxidative damage in the liver by decreasing level of MDA levels and increasing the antioxidant related by enzymes in the liver homogenates compared to the control rats. These effects were more evident when the two agents were administered together. Conclusion. The combined intake of honey and olive oil could be hepatoprotective. Co-administration of these agents might form an effective adjuvant therapy and minimize side effects of chemoherapy in cancerous patients

Neuroprotective Effect of Red Sea Marine Sponge <i>Xestospongia testudinaria</i> Extract Using In Vitro and In Vivo Diabetic Peripheral Neuropathy Models

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. Oxidative stress plays an important role in the pathophysiology of DPN. Red Sea marine sponge Xestospongia testudinaria extract has a promising neuroprotective effect, presumably owing to its antioxidant and anti-inflammatory properties. Thus, this study aimed to investigate the neuroprotective effect of the sponge X. testudinaria extract on in vitro and in vivo models of DPN. Mice dorsal root ganglia (DRG) were cultured with high glucose (HG) media and used as an in vitro model of DPN. Some of the DRGs were pre-treated with 2 mg/mL of X. testudinaria. The X. testudinaria extract significantly improved the HG-induced decreased neuronal viability and the neurite length. It improved the oxidative stress biomarkers in DRG cultures. The DPN model was induced in vivo by an injection of streptozotocin at a dose of 150 mg/kg in mice. After 35 days, 0.75 mg/kg of the X. testudinaria extract improved the hot hyperalgesia and the DRG histology. Although the sponge extract did not reduce hyperglycemia, it ameliorated the oxidative stress markers and pro-inflammatory markers in the DRG. In conclusion, the current study demonstrates the neuroprotective effect of Red Sea sponge X. testudinaria extract against experimentally induced DPN through its antioxidant and anti-inflammatory mechanisms