ABSTRACT
Muscular dystrophy is a heterogenous group of hereditary muscle disorders caused by mutations in the genes responsible for muscle development, and is generally defined by a disastrous progression of muscle wasting and massive loss in muscle regeneration. Pax7 is closely associated with myogenesis, which is governed by various signaling pathways throughout a lifetime and is frequently used as an indicator in muscle research. In this review, an extensive literature search adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed to identify research that examined signaling pathways in living models, while quantifying Pax7 expression in myogenesis. A total of 247 articles were retrieved from the Web of Science (WoS), PubMed and Scopus databases and were thoroughly examined and evaluated, resulting in 19 articles which met the inclusion criteria. Admittedly, we were only able to discuss the quantification of Pax7 carried out in research affecting various type of genes and signaling pathways, rather than the expression of Pax7 itself, due to the massive differences in approach, factor molecules and signaling pathways analyzed across the research. However, we highlighted the thorough evidence for the alteration of the muscle stem cell precursor Pax7 in multiple signaling pathways described in different living models, with an emphasis on the novel approach that could be taken in manipulating Pax7 expression itself in dystrophic muscle, towards the discovery of an effective treatment for muscular dystrophy. Therefore, we believe that this could be applied to the potential gap in muscle research that could be filled by tuning the well-established marker expression to improve dystrophic muscle.
Subject(s)
Muscular Dystrophies , Humans , Muscular Dystrophies/genetics , Muscles , Databases, Factual , Muscle Development , Signal Transduction , PAX7 Transcription Factor/geneticsABSTRACT
Respiratory diseases recently became the leading cause of death worldwide, due to the emergence of COVID-19. The pathogenesis of respiratory diseases is centred around inflammation and oxidative stress. Plant-based alongside synthetic drugs were considered as therapeutics due to their proven nutraceutical value. One such example is the olive, which is a traditional symbol of the MedDiet. Olive bioactive compounds are enriched with antioxidant, anti-inflammatory, anticancer and antiviral properties. However, there are few studies relating to the beneficial effect of olive bioactive compounds on respiratory diseases. A vague understanding of its molecular action, dosage and bioavailability limits its usefulness for clinical trials about respiratory infections. Hence, our review aims to explore olive bioactive compound's antioxidant, anti-inflammatory and antiviral properties in respiratory disease defence and treatment. Molecular insight into olive compounds' potential for respiratory system protection against inflammation and ensuing infection is also presented. Olive bioactive compounds mainly protect the respiratory system by subsiding proinflammatory cytokines and oxidative stress.
ABSTRACT
Oxidative stress is one of the factors involved in the pathogenesis of several neurodegenerative diseases. It has been reported that a secretory phospholipase A2 known as A2-EPTX-NSm1a has lower cytotoxicity in neuronal cells compared to its crude Naja sumatrana venom. In this study, A2-EPTX-NSm1a was tested for its neuroprotective activity on human neuroblastoma cells (SH-SY5Y) differentiated into cholinergic neurons against oxidative stress induced by hydrogen peroxide (H2O2). H2O2 treatment alone increased the caspase-3 and caspase-8 activities, whereas pre-treatment with A2-EPTX-NSm1a reduced the activity of these apoptosis-associated proteins. Moreover, A2-EPTX-NSm1a protects the morphology and ultrastructure of differentiated SH-SY5Y cells in the presence of H2O2. Oxidative stress increased the number of small mitochondria. Further evaluation showed the size of mitochondria with a length below 0.25 µm in oxidative stress conditions is higher than the control group, suggesting mitochondria fragmentation. Pre-treatment with A2-EPTX-NSm1a attenuated the number of mitochondria in cells with H2O2 Furthermore, A2-EPTX-NSm1a altered the expression of several neuroprotein biomarkers of GDNF, IL-8, MCP-1, TIMP-1, and TNF-R1 in cells under oxidative stress induced by H2O2. These findings indicate that anti-apoptosis with mitochondria-related protection, anti-inflammatory effect, and promote expression of important markers for cell survival may underlie the neuroprotective effect of A2-EPTX-NSm1a in cholinergic rich human cells under oxidative stress, a vital role in the neuronal disorder.
ABSTRACT
Phospholipase A2 (PLA2) toxins are one of the main toxin families found in snake venom. PLA2 toxins are associated with various detrimental effects, including neurotoxicity, myotoxicity, hemostatic disturbances, nephrotoxicity, edema, and inflammation. Although Naja sumatrana venom contains substantial quantities of PLA2 components, there is limited information on the function and activities of PLA2 toxins from the venom. In this study, a secretory PLA2 from the venom of Malaysian N. sumatrana, subsequently named A2-EPTX-Nsm1a, was isolated, purified, and characterized. A2-EPTX-Nsm1a was purified using a mass spectrometry-guided approach and multiple chromatography steps. Based on LC-MSMS, A2-EPTX-Nsm1a was found to show high sequence similarity with PLA2 from venoms of other Naja species. The PLA2 activity of A2-EPTX-Nsm1 was inhibited by 4-BPB and EDTA. A2-EPTX-Nsm1a was significantly less cytotoxic in a neuroblastoma cell line (SH-SY5Y) compared to crude venom and did not show a concentration-dependent cytotoxic activity. To our knowledge, this is the first study that characterizes and investigates the cytotoxicity of an Asp49 PLA2 isolated from Malaysian N. sumatrana venom in a human neuroblastoma cell line.
